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  • 1. Aare, Magnus
    et al.
    von Holst, Hans
    KTH, School of Technology and Health (STH), Neuronic Engineering.
    Injuries from motorcycle- and moped crashes in Sweden from 1987 to 1999.2003In: Injury control and safety promotion, ISSN 1566-0974, E-ISSN 1744-4985, Vol. 10, no 3, p. 131-8Article in journal (Refereed)
    Abstract [en]

    The objective of this paper is to study injuries from motorcycle and moped crashes in Sweden from 1987 to 1999. Databases at the National Board for Health and Welfare and codes from both ICD9 and ICD10 systems were used, including patterns of age, gender, E-code and type of injury. Length of hospital stay, type of injuries and trends over time was evaluated. To get a more detailed picture of the age distribution, type of vehicle used and number of killed, data from the Swedish National Road Administration were also used. In Sweden, 27,122 individuals received in-patient care due to motorcycle and moped injuries between 1987 and 1999. The motorcycle and moped injury rate was reduced in the second half of the studied period and so were the total days of treatment per year. Males had eight times the incidence of injuries compared to females. Riders under the age of 26 and in particular those at an age of 15 had the highest incidence rate. Head injuries were the most frequent diagnosis, followed by fractures to the lower limbs. Concussion was the most frequent head injury. Focal and diffuse brain injuries combined showed the same frequency as concussion. It is concluded that more preventative strategies must be presented before the injury rate can be reduced.

  • 2. Aartsma-Rus, A.
    et al.
    Ferlini, A.
    McNally, E. M.
    Spitali, P.
    Sweeney, H. L.
    Al-Khalili Szigyarto, Cristina
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Bello, L.
    Bronson, A.
    Brown, K.
    Buccella, F.
    Chadwick, J.
    Frank, D.
    Hoffman, E.
    Larkindale, J.
    McClorey, G.
    Munschauer, R.
    Muntoni, F.
    Owens, J.
    Schara, U.
    Straub, V.
    Tinsley, J.
    Versnel, J.
    Vroom, E.
    Welch, E.
    226th ENMC International Workshop:: Towards validated and qualified biomarkers for therapy development for Duchenne muscular dystrophy 20–22 January 2017, Heemskerk, The Netherlands2018In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 28, no 1, p. 77-86Article in journal (Refereed)
  • 3.
    Abaid, Mohammed Abderhman
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Ergonomics.
    Validation of a new iPhone application for measurements of wrist velocity during actual work tasks2023Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The breakthrough in mobile technology and the development of smartphones, supplied with sensing devices such as Inertial Measurement Units (IMUs), has made it possible to obtain accurate and reliable data on the angular velocity for different objects. The available technical sensors for wrist movements, such as electrogoniometers, are costly, time-consuming, and need a particular computer program to be analyzed. Therefore, there is a need to develop user-friendly risk assessment methods for wrist angular velocity measurements. This master thesis aimed to validate the accuracy of a newly developed iPhone application (App), "ErgoHandMeter," for wrist velocity in actual work tasks, by comparing the “ErgoHandMeter” to standard electrogoniometers. The project study was performed with four participants, two females and two males, from three jobs performing actual work tasks. The total angular velocity obtained by the mobile application was compared with the angular velocity data from the standard electrogoniometer. The total angular velocities obtained from the smartphone and the goniometer were computed at the 10th, 50th and 90th percentile for the four subjects. The 50th percentile of goniometer-flexion velocity (G-flex) was 7.4 ± 5.4°/s, for the goniometer-total (G-tot) 8.7 ± 6.5)°/s and for App 7.2 ± 4.9°/s. The correlation coefficient for the 50th percentile of goniometer-flexion (G-flex) parameter and smartphone application was 0.994. For the goniometer-total (G-tot) and the application, it was 0.993. In a Bland-Altman plot the mean difference between G-flex and App for the 50th percentile was -0.18 °/s and for G-tot and App was -1.54 °/s, i.e. the App was lower in average. The limit of the agreement between G-Flex and App, and G-tot and App stayed within two standard deviations. For G-Flex and App (mean+1.96SD) was 1.34 °/s, (mean-1.96SD) was -1.71 °/s, while for G-tot and App (mean+1.96SD) was 1.89 °/s, (mean-1.96SD) was -4.96 °/s, indicating an adequate agreement between the two methods. A limitation was that the included occupations were all relatively low velocity. However, in conclusion, the results indicate that the two methods agree adequately and can be used interchangeably.

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  • 4.
    Abbasi Aval, Negar
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Utilizing Biopolymers in 3D Tumor Modeling and Tumor Diagnosis2023Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cancer represents a significant global public health challenge and ranks as the second mostcommon cause of death in the United States. The onset of cancer entails an initial phasewhere cells lose their polarity and disconnect from the normal basement membrane, allowingthem to form distinct three-dimensional (3D) configurations that interact with adjacent cellsand the surrounding microenvironment. Cells grown in 2D monolayers demonstrate differentgene expression patterns and different activation of signaling pathways compared to cellscultivated within the natural structure of tumor tissue of the same cell type. Multicellulartumor spheroids (MCTS) are extensively investigated as a well-studied model of organotypiccancer. These spheroids are formed by tumor cells, either alone or in combination with othercell types, and they can be created with or without the application of supportive scaffolds.The MCTSs are also considered promising models for preclinical assessments of chemosensitivity.However, the creation of these tumor spheroids presents challenges, as not alltumor cell lines can consistently form regular spheroids.Cellulose nanofibrils (CNF) have become essential as a sustainable and environmentallyfriendly material. For example, thin films, with inherent mechanical properties, and flexibility,offer versatility across various applications. Also known for its biocompatibility and non-toxicnature, native CNF is a natural option to use. Its fibrous structure closely mimics the collagenmatrix in human tissue, showing potential as an effective scaffold for 3D cell culture. In thisregard, an innovative Layer-by-Layer (LbL) coating technique using CNF-polyelectrolytebilayers was investigated to generate spheroids. This method constructs bilayers of CNFand polyelectrolytes and can coat various surfaces. In this thesis, the first focus was ondemonstrating the spheroid formation capability using low molecular weight polyelectrolytesin LbL assembly. Secondly, an investigation was conducted involving embedding of LbLgrownspheroids in a decellularized extracellular matrix (ECM) aiming to determine howECM, possessing suitable mechanical characteristics, could influence the cancer stem celltraits in spheroids. Thirdly, the thesis demonstrated the utilization of LbL for capturing andreleasing of circulating tumor cells. Lastly, the shift from using low molecular weightpolyelectrolytes in the LbL assembly to high molecular weight counterparts and analyzingthe differences in spheroid formation abilities to assess the underlying differences inmolecular weights of the polyelectrolytes was explored. All-in-all, employing the CNF-basedLbL surface coating strategy explored in the thesis has proven to be promising for thedevelopment of spheroid models closely resembling in vivo conditions and holds significantpotential for applications in drug development.

  • 5.
    Abbasi Aval, Negar
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Khati, Vamakshi
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Pettersson, Torbjörn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Russom, Aman
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Layer-by-Layer cellulose nanofibril coating for spheroid formation combined with decellularized extracellular matrix for 3D tumor modelingManuscript (preprint) (Other academic)
  • 6.
    Abbasi Aval, Negar
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Khati, Vamakshi
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Russom, Aman
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Pettersson, Torbjörn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Influence of Decellularized Extra Cellular Matrix on 3D spheroids formed on Layer-by-Layer cellulose nanofibril/Polyelectrolytes coating as an in-vitro model for Hepatocellular CarcinomaManuscript (preprint) (Other academic)
  • 7.
    Abbasi Aval, Negar
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Lahchaichi, Ekeram
    Fayazbakhsh, Farzaneh
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Tudoran, Oana
    Russom, Aman
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Pettersson, Torbjörn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Evaluating the Impact of Positively Charged Polyelectrolyte Molecular Weightand Bilayer Number on Tumor Spheroid Formation in the Interaction with Negatively Charged Cellulose Nanofibrils in layer by layer assembly2023Manuscript (preprint) (Other academic)
  • 8.
    Abbasi Aval, Negar
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Lahchaichi, Ekeram
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Tudoran, Oana
    Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. I. Chiricuta”, 400015 Cluj-Napoca, Romania.
    Fayazbakhsh, Farzaneh
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Heuchel, Rainer
    Pancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology, (CLINTEC), Karolinska Institutet, 17177 Stockholm, Sweden.
    Löhr, Matthias
    Pancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology, (CLINTEC), Karolinska Institutet, 17177 Stockholm, Sweden.
    Pettersson, Torbjörn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Russom, Aman
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Assessing the Layer-by-Layer Assembly of Cellulose Nanofibrils and Polyelectrolytes in Pancreatic Tumor Spheroid Formation2023In: Biomedicines, E-ISSN 2227-9059, Vol. 11, no 11Article in journal (Refereed)
    Abstract [en]

    Three-dimensional (3D) tumor spheroids are regarded as promising models for utilization as preclinical assessments of chemo-sensitivity. However, the creation of these tumor spheroids presents challenges, given that not all tumor cell lines are able to form consistent and regular spheroids. In this context, we have developed a novel layer-by-layer coating of cellulose nanofibril–polyelectrolyte bilayers for the generation of spheroids. This technique builds bilayers of cellulose nanofibrils and polyelectrolytes and is used here to coat two distinct 96-well plate types: nontreated/non-sterilized and Nunclon Delta. In this work, we optimized the protocol aimed at generating and characterizing spheroids on difficult-to-grow pancreatic tumor cell lines. Here, diverse parameters were explored, encompassing the bilayer count (five and ten) and multiple cell-seeding concentrations (10, 100, 200, 500, and 1000 cells per well), using four pancreatic tumor cell lines—KPCT, PANC-1, MiaPaCa-2, and CFPAC-I. The evaluation includes the quantification (number of spheroids, size, and morphology) and proliferation of the produced spheroids, as well as an assessment of their viability. Notably, our findings reveal a significant influence from both the number of bilayers and the plate type used on the successful formation of spheroids. The novel and simple layer-by-layer-based coating method has the potential to offer the large-scale production of spheroids across a spectrum of tumor cell lines.

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  • 9.
    Abbasi, Saeed
    et al.
    KTH, School of Industrial Engineering and Management (ITM), Machine Design (Dept.), Machine Elements.
    Ekstrand-Hammarström, Barbara
    Division of CBRN Defence and Security, Swedish Defence Research Agency (FOI),.
    Bergström, Ulrika
    Division of CBRN Defence and Security, Swedish Defence Research Agency (FOI),.
    Bucht, Anders
    Deptartment of Public Health and Clinical Medicine, Umeå University Hospital, Umeå, 901 89, Sweden.
    Olofsson, Ulf
    KTH, School of Industrial Engineering and Management (ITM), Machine Design (Dept.), Machine Elements.
    Sellgren, Ulf
    KTH, School of Industrial Engineering and Management (ITM), Machine Design (Dept.), Machine Elements.
    Jansson, Anders
    Department of Applied Environmental Science, Stockholm University, Stockholm, 106 91, Sweden.
    Biological response in lung cells by brake dust from a novel set-up to generate one sourcewear particles2013Conference paper (Refereed)
  • 10.
    Abdellah, Tebani
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Normandie Univ, Dept Metab Biochem, UNIROUEN, INSERM,U1245,CHU Rouen, F-76000 Rouen, France..
    Jotanovic, Jelena
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.;Uppsala Univ Hosp, Dept Clin Pathol, Uppsala, Sweden..
    Hekmati, Neda
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Sivertsson, Åsa
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Gudjonsson, Olafur
    Uppsala Univ, Dept Neurosci, Uppsala, Sweden..
    Engstrom, Britt Eden
    Uppsala Univ, Dept Med Sci Endocrinol & Mineral Metab, Uppsala, Sweden..
    Wikstrom, Johan
    Uppsala Univ, Dept Surg Sci, Neuroradiol, Uppsala, Sweden..
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Casar-Borota, Olivera
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.;Uppsala Univ Hosp, Dept Clin Pathol, Uppsala, Sweden..
    Ponten, Fredrik
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Annotation of pituitary neuroendocrine tumors with genome-wide expression analysis2021In: Acta neuropathologica communications, E-ISSN 2051-5960, Vol. 9, no 1, article id 181Article in journal (Refereed)
    Abstract [en]

    Pituitary neuroendocrine tumors (PitNETs) are common, generally benign tumors with complex clinical characteristics related to hormone hypersecretion and/or growing sellar tumor mass. PitNETs can be classified based on the expression pattern of anterior pituitary hormones and three main transcriptions factors (TF), SF1, PIT1 and TPIT that regulate differentiation of adenohypophysial cells. Here, we have extended this classification based on the global transcriptomics landscape using tumor tissue from a well-defined cohort comprising 51 PitNETs of different clinical and histological types. The molecular profiles were compared with current classification schemes based on immunohistochemistry. Our results identified three main clusters of PitNETs that were aligned with the main pituitary TFs expression patterns. Our analyses enabled further identification of specific genes and expression patterns, including both known and unknown genes, that could distinguish the three different classes of PitNETs. We conclude that the current classification of PitNETs based on the expression of SF1, PIT1 and TPIT reflects three distinct subtypes of PitNETs with different underlying biology and partly independent from the expression of corresponding hormones. The transcriptomic analysis reveals several potentially targetable tumor-driving genes with previously unknown role in pituitary tumorigenesis.

  • 11.
    Abduljabar, Haya
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems.
    Hadi, Hanan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems.
    Sterilization of Medical Equipment in a Third World Country: A Minor Field Study in Linga Linga, Mozambique2020Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The non-profit organization Project Vita has recently built a maternity clinic in Linga Linga, where the medical instruments to be sterilized are boiled in water for an hour. The fuel needed to boil the water is wood, which is a scarce resource. This is why, according to the healthcare worker that was interviewed in Mozambique, it is desirable to have an electric-powered solution to sterilise the medical instruments.

    After research on the different sterilization techniques that exist, the conclusion was drawn that the safest way to sterilise is by the use of an autoclave. However, it would be difficult to implement and maintain an autoclave in Linga Linga. Therefore, it was proposed to build an autoclave using a pressure cooker. Through experimentation, different programs, times and pressures were tested to find out if a pressure cooker could sterilise a common object. It could be concluded that theoretically, it seems that the pressure cooker reached a temperature of over 121 degrees Celsius. However, the pressure could not be measured nor was a biological indicator, that could indicate if an autoclave or pressure cooker does sterile, used. 

    This project was to be done in Mozambique, but because of COVID-19, a travel ban was set in motion and universities and laboratories had limited access, thus limiting the project. As a result, it is still unclear if a pressure cooker can be used to sterilize medical instruments.

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  • 12. Aberg, A. C.
    et al.
    Thorstensson, A.
    Tarassova, O.
    Halvorsen, Kjartan
    KTH, School of Technology and Health (STH).
    Calculations of mechanisms for balance control during narrow and single-leg standing in fit older adults: A reliability study2011In: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 34, no 3, p. 352-357Article in journal (Refereed)
    Abstract [en]

    For older people balance control in standing is critical for performance of activities of daily living without falling. The aims were to investigate reliability of quantification of the usage of the two balance mechanisms M(1) 'moving the centre of pressure' and M(2) 'Segment acceleration' and also to compare calculation methods based on a combination of kinetic (K) and kinematic (Km) data, (K-Km), or Km data only concerning M(2). For this purpose nine physically fit persons aged 70-78 years were tested in narrow and single-leg standing. Data were collected by a 7-camera motion capture system and two force plates. Repeated measure ANOVA and Tukey's post hoc tests were used to detect differences between the standing tasks. Reliability was estimated by ICCs, standard error of measurement including its 95% Cl, and minimal detectable change, whereas Pearson's correlation coefficient was used to investigate agreement between the two calculation methods. The results indicated that for the tasks investigated, M(1) and M(2) can be measured with acceptable inter- and intrasession reliability, and that both Km and K-Km based calculations may be useful for M(2), although Km data may give slightly lower values. The proportional M(1) :M(2) usage was approximately 9:1, in both anterio-posterior (AP) and medio-lateral (ML) directions for narrow standing, and about 2:1 in the AP and of 1:2 in the ML direction in single-leg standing, respectively. In conclusion, the tested measurements and calculations appear to constitute a reliable way of quantifying one important aspect of balance capacity in fit older people.

  • 13.
    Aberg, Anna Cristina
    et al.
    Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, BMC, Box 564, SE-75122 Uppsala, Sweden.;Dalarna Univ, Sch Hlth & Welf, SE-79188 Falun, Sweden..
    Olsson, Fredrik
    KTH, School of Engineering Sciences (SCI), Engineering Mechanics.
    Ahman, Hanna Bozkurt
    Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, BMC, Box 564, SE-75122 Uppsala, Sweden..
    Tarassova, Olga
    Swedish Sch Sport & Hlth Sci, Lidingovagen 1, SE-11486 Stockholm, Sweden..
    Arndt, Anton
    Swedish Sch Sport & Hlth Sci, Lidingovagen 1, SE-11486 Stockholm, Sweden.;Karolinska Inst, SE-17177 Stockholm, Sweden..
    Giedraitis, Vilmantas
    Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, BMC, Box 564, SE-75122 Uppsala, Sweden.;Dalarna Univ, Sch Hlth & Welf, SE-79188 Falun, Sweden..
    Berglund, Lars
    Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, BMC, Box 564, SE-75122 Uppsala, Sweden.;Dalarna Univ, Sch Hlth & Welf, SE-79188 Falun, Sweden..
    Halvorsen, Kjartan
    Dalarna Univ, Sch Hlth & Welf, SE-79188 Falun, Sweden.;Tecnol Monterrey, Sch Sci & Engn, Dept Mechatron, Campus Estado Mexico, Atizapan 52926, Estado Mexico, Mexico..
    Extraction of gait parameters from marker-free video recordings of Timed Up-and-Go tests: Validity, inter- and intra-rater reliability2021In: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 90, p. 489-495Article in journal (Refereed)
    Abstract [en]

    Background: We study dual-task performance with marker-free video recordings of Timed Up-and-Go tests (TUG) and TUG combined with a cognitive/verbal task (TUG dual-task, TUGdt). Research question: Can gait parameters be accurately estimated from video-recorded TUG tests by a new semiautomatic method aided by a technique for human 2D pose estimation based on deep learning? Methods: Thirty persons aged 60-85 years participated in the study, conducted in a laboratory environment. Data were collected by two synchronous video-cameras and a marker-based optoelectronic motion capture system as gold standard, to evaluate the gait parameters step length (SL), step width (SW), step duration (SD), single-stance duration (SSD) and double-stance duration (DSD). For reliability evaluations, data processing aided by a deep neural network model, involved three raters who conducted three repetitions of identifying anatomical keypoints in recordings of one randomly selected step from each of the participants. Validity was analysed using 95 % confidence intervals (CI) and p-values for method differences and Bland-Altman plots with limits of agreement. Inter- and intra-rater reliability were calculated as intraclass correlation coefficients (ICC) and standard errors of measurement. Smallest detectable change was calculated for inter-rater reliability. Results: Mean ddifferences between video and the motion capture system data for SW, DSD, and SSD were significant (p < 0.001). However, mean differences for all parameters were small (-6.4%-13.0% of motion capture system) indicating good validity. Concerning reliability, almost all 95 % CI of the ICC estimates exceeded 0.90, indicating excellent reliability. Only inter-rater reliability for SW (95 % CI = 0.892;0.973) and one rater's intrarater reliability for SSD (95 % CI = 0.793;0.951) were lower, but still showed good to excellent reliability. Significance: The presented method for extraction of gait parameters from video appears suitable for valid and reliable quantification of gait. This opens up for analyses that may contribute to the knowledge of cognitivemotor interference in dual-task testing.

  • 14. Aberg, B
    et al.
    Koul, B L
    Liska, J
    Brodin, L A
    KTH, School of Technology and Health (STH).
    Landou, C
    Delayed left ventricular free wall rupture complicating coronary artery bypass surgery. A case report.1985In: Scandinavian journal of thoracic and cardiovascular surgery, ISSN 0036-5580, Vol. 19, no 3, p. 273-7Article in journal (Refereed)
    Abstract [en]

    Rupture of the left ventricular free wall is a not uncommon life-threatening complication of acute myocardial infarction and after prosthetic mitral valve replacement. To our knowledge, no case of left ventricular rupture after coronary artery bypass surgery has been reported. A case is now described in which coronary artery bypass grafting was complicated by delayed rupture, which was successfully repaired. Different etiologic factors are discussed, but the cause considered most likely was trauma from elevation of and traction on the heart in exposure of its posterior aspect.

  • 15.
    Abhishek, Sarabjot
    et al.
    Dr BR Ambedkar Natl Inst Technol, Dept Phys, GT Rd Bye Pass, Jalandhar 144027, Punjab, India..
    Kaur, Sarabjot
    KTH, School of Engineering Sciences (SCI), Physics, Nuclear Physics.
    Mehra, Rohit
    Dr BR Ambedkar Natl Inst Technol, Dept Phys, GT Rd Bye Pass, Jalandhar 144027, Punjab, India..
    Estimation of Uranium and Related Health Risks Due to Consumption of Groundwater in Lower Himalayas2023In: Indian Journal of Pure & Applied Physics, ISSN 0019-5596, E-ISSN 0975-1041, Vol. 61, no 6, p. 478-483Article in journal (Refereed)
    Abstract [en]

    Exposure to uranium via ingestion of edible products may lead to serious health hazards when taken in quantities more than recommended limit. Hence, to assess the uranium content in groundwater and concerned health hazards 64 groundwater samples were collected from Hamirpur and Mandi districts of Himachal Pradesh. The samples were collected in pre monsoon season from the handpumps and bowries. The region lies in Lower Himalayan range which is storehouse of various granatic rocks. Presence of uranium deposits in Tileli (Mandi), Rajpura (Una), Lambehra (Hamirpur) makes the area more vulnerable for the study. The groundwater samples were analysed to measure concentration of uranium using LED Fluorimeter developed by Quantalase Private. Limited. The uranium concentration in groundwater samples varied from 0.25 to 17.29 & mu;g L-1, with an average value of 1.97. Uranium concentration in none of the samples surpassed the limit of 30 & mu;g L-1 recommended by WHO(2011), 60 & mu;g L-1 set by AERB(2004). Health risks were estimated in terms radiological and chemical toxicity for different isotopes of uranium. The calculated average mortality and morbidity risks were lower than the actual prescribed limit. The average Lifetime Average Daily Dose (LADD) was calculated as 0.04 and Hazard Quotient (HQ) below unity. Annual ingestion doses for different age groups were also measured which lies under safe limit. Thus, it is recommended that the groundwater is safe for consumption by public. Using Hair Compartment Model for uranium and mean daily uranium intake of 2.71 & mu;g for 60-year exposure period, organ specific doses due to uranium radioisotopes in prime organs/tissues and excretion rates via urine, faeces and hair pathway are estimated.

  • 16.
    Abourraja, Mohamed Nezar
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Health Informatics and Logistics.
    Marzano, Luca
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Health Informatics and Logistics.
    Raghothama, Jayanth
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Health Informatics and Logistics.
    Boodaghian Asl, Arsineh
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Health Informatics and Logistics.
    Darwich, Adam S.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Health Informatics and Logistics.
    Meijer, Sebastiaan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Health Informatics and Logistics.
    Lethvall, Sven
    Uppsala University Hospital,Uppsala,Sweden.
    Falk, Nina
    Uppsala University Hospital,Uppsala,Sweden.
    A Data-Driven Discrete Event Simulation Model to Improve Emergency Department Logistics2022In: Proceedings of the 2022 Winter Simulation Conference, Institute of Electrical and Electronics Engineers (IEEE) , 2022Conference paper (Refereed)
    Abstract [en]

    Demands for health care are becoming overwhelming for healthcare systems around the world regarding theavailability of resources, particularly, in emergency departments (EDs) that are continuously open and mustserve immediately any patient who comes in. Efficient management of EDs and their resources is requiredmore than ever. This could be achieved either by optimizing resource utilization or by the improvement ofhospital layout. This paper investigates, through data-driven simulation alternative designs of workflowsand layouts to operate the ED of the Uppsala University Hospital in Sweden. Results are analyzed tounderstand the requirements across the hospital for reduced waiting times in the ED. The main observationrevealed that introducing a new ward dedicated to patients having complex diagnoses with a capacity ofless than 20 beds leads to lower waiting times. Furthermore, the use of data-mining was of great help inreducing the efforts of building the simulation model.

  • 17.
    Abourraja, Mohamed Nezar
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Health Informatics and Logistics.
    Meijer, Sebastiaan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Health Informatics and Logistics.
    Boukachour, Jaouad
    Normandie University, UNIHAVRE, 76600 Le Havre, France.
    A model-driven design approach for Ro-Ro and container terminals: from requirements analysis down to simulation model implementation2021In: 20th International Conference on Modeling and Applied Simulation, MAS 2021, Cal-Tek Srl , 2021, p. 9-20Conference paper (Refereed)
    Abstract [en]

    Modeling, one of the main pillars of good scientific research, is a long-standing multidisciplinary activity to understand and analyze complex systems. In this paper, the focus is directed toward conceptual modeling of multi-terminal seaports specialized in handling and treatment of intermodal transport units (ITU). These systems are complex with highly dynamic and stochastic behaviors and actors, therefore, studying them as a coherent whole or just analyzing one part by taking into account the high degree of integration among the different aspects and actors linked by a flow of activities, information, and interactions is a bet lost in advance without a well-defined design process. Several design approaches and methodologies have been proposed over the years, but nonetheless, there is still no agreement on how to conduct modeling of complex systems because they are of different kinds. In this line, this paper proposes a top-down approach for container and Ro-Ro terminals largely inspired by the Unified Process Methodology and refined through several research projects that we have been involved in. It gives some recommendations and guidelines as well as a helpful way to successfully build modular and consistent simulation models. To prove its efficiency, it was applied to a case study and the resulting models were validated by the subject matter's experts.

  • 18.
    Abouzayed, Ayman
    et al.
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden..
    Borin, Jesper
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Technology.
    Lundmark, Fanny
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden..
    Rybina, Anastasiya
    Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Med, Tomsk 634009, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia..
    Hober, Sophia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Zelchan, Roman
    Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Med, Tomsk 634009, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia..
    Tolmachev, Vladimir
    Uppsala Univ, Dept Immunol Genet & Pathol, S-75237 Uppsala, Sweden..
    Chernov, Vladimir
    Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Med, Tomsk 634009, Russia..
    Orlova, Anna
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden.;Uppsala Univ, Sci Life Lab, S-75237 Uppsala, Sweden..
    The GRPR Antagonist [Tc-99m]Tc-maSSS-PEG(2)-RM26 towards Phase I Clinical Trial: Kit Preparation, Characterization and Toxicity2023In: Diagnostics, ISSN 2075-4418, Vol. 13, no 9, p. 1611-, article id 1611Article in journal (Refereed)
    Abstract [en]

    Gastrin-releasing peptide receptors (GRPRs) are overexpressed in the majority of primary prostate tumors and in prostatic lymph node and bone metastases. Several GRPR antagonists were developed for SPECT and PET imaging of prostate cancer. We previously reported a preclinical evaluation of the GRPR antagonist [Tc-99m]Tc-maSSS-PEG2-RM26 (based on [D-Phe(6), Sta(13), Leu(14)-NH2]BBN(6-14)) which bound to GRPR with high affinity and had a favorable biodistribution profile in tumor-bearing animal models. In this study, we aimed to prepare and test kits for prospective use in an early-phase clinical study. The kits were prepared to allow for a one-pot single-step radiolabeling with technetium-99m pertechnetate. The kit vials were tested for sterility and labeling efficacy. The radiolabeled by using the kit GRPR antagonist was evaluated in vitro for binding specificity to GRPR on PC-3 cells (GRPR-positive). In vivo, the toxicity of the kit constituents was evaluated in rats. The labeling efficacy of the kits stored at 4 degrees C was monitored for 18 months. The biological properties of [Tc-99m]Tc-maSSS-PEG2-RM26, which were obtained after this period, were examined both in vitro and in vivo. The one-pot (gluconic acid, ethylenediaminetetraacetic acid, stannous chloride, and maSSS-PEG(2)-RM26) single-step radiolabeling with technetium-99m was successful with high radiochemical yields (>97%) and high molar activities (16-24 MBq/nmol). The radiolabeled peptide maintained its binding properties to GRPR. The kit constituents were sterile and non-toxic when tested in living subjects. In conclusion, the prepared kit is considered safe in animal models and can be further evaluated for use in clinics.

  • 19.
    Abouzayed, Ayman
    et al.
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden..
    Tano, Hanna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.
    Nagy, Abel
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Rinne, Sara S.
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden..
    Wadeea, Fadya
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden..
    Kumar, Sharmishtaa
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Westerlund, Kristina
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.
    Tolmachev, Vladimir
    Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden..
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH Royal Inst Technol, AlbaNova Univ Ctr, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden..
    Orlova, Anna
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Centrum Oncotheranost, Tomsk 634050, Russia.;Uppsala Univ, Sci Life Lab, S-75105 Uppsala, Sweden..
    Preclinical Evaluation of the GRPR-Targeting Antagonist RM26 Conjugated to the Albumin-Binding Domain for GRPR-Targeting Therapy of Cancer2020In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 12, no 10, article id 977Article in journal (Refereed)
    Abstract [en]

    The targeting of gastrin-releasing peptide receptors (GRPR) was recently proposed for targeted therapy, e.g., radiotherapy. Multiple and frequent injections of peptide-based therapeutic agents would be required due to rapid blood clearance. By conjugation of the GRPR antagonist RM26 (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) to an ABD (albumin-binding domain), we aimed to extend the blood circulation of peptides. The synthesized conjugate DOTA-ABD-RM26 was labelled with indium-111 and evaluated in vitro and in vivo. The labelled conjugate was stable in PBS and retained specificity and its antagonistic function against GRPR. The half-maximal inhibitory concentration (IC50) of In-nat-DOTA-ABD-RM26 in the presence of human serum albumin was 49 +/- 5 nM. [In-111]In-DOTA-ABD-RM26 had a significantly longer residence time in blood and in tumors (without a significant decrease of up to 144 h pi) than the parental RM26 peptide. We conclude that the ABD-RM26 conjugate can be used for GRPR-targeted therapy and delivery of cytotoxic drugs. However, the undesirable elevated activity uptake in kidneys abolishes its use for radionuclide therapy. This proof-of-principle study justified further optimization of the molecular design of the ABD-RM26 conjugate.

  • 20. Abrahamsson, T. R.
    et al.
    Jakobsson, H. E.
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Björkstén, B.
    Engstrand, Lars
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Jenmalm, M. C.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 6, p. 842-850Article in journal (Refereed)
    Abstract [en]

    Background Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age. Objective To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema. Methods The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1week, 1month and 12months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7years of age (ClinicalTrials.gov ID NCT01285830). Results Children developing asthma (n=8) had a lower diversity of the total microbiota than non-asthmatic children at 1week (P=0.04) and 1month (P=0.003) of age, whereas allergic rhinoconjunctivitis (n=13), eczema (n=12) and positive skin prick reactivity (n=14) at 7years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease. Conclusion and Clinical Relevance Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.

  • 21.
    Abramson, Alex
    et al.
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA..
    Caffarel-Salvador, Ester
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.;MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Khang, Minsoo
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA..
    Dellal, David
    MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Silverstein, David
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA..
    Gao, Yuan
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA..
    Frederiksen, Morten Revsgaard
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Vegge, Andreas
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Hubalek, Frantisek
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Water, Jorrit J.
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Friderichsen, Anders V.
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Fels, Johannes
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Kirk, Rikke Kaae
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Cleveland, Cody
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.;Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Collins, Joy
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA..
    Tamang, Siddartha
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA..
    Hayward, Alison
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.;MIT, Div Comparat Med, Cambridge, MA 02139 USA..
    Landh, Tomas
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Buckley, Stephen T.
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Rahbek, Ulrik
    Novo Nordisk AS, Global Res Technol, Global Drug Discovery & Device R&D, Copenhagen, Denmark..
    Langer, Robert
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.;MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Media Lab, Cambridge, MA 02139 USA..
    Traverso, Giovanni
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, Cambridge, MA 02139 USA.;Harvard Med Sch, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA..
    An ingestible self-orienting system for oral delivery of macromolecules2019In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 363, no 6427, p. 611-+Article in journal (Refereed)
    Abstract [en]

    Biomacromolecules have transformed our capacity to effectively treat diseases; however, their rapid degradation and poor absorption in the gastrointestinal (GI) tract generally limit their administration to parenteral routes. An oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake. Inspired by the leopard tortoise's ability to passively reorient, we developed an ingestible self-orienting millimeter-scale applicator (SOMA) that autonomously positions itself to engage with GI tissue. It then deploys milliposts fabricated from active pharmaceutical ingredients directly through the gastric mucosa while avoiding perforation. We conducted in vivo studies in rats and swine that support the applicator's safety and, using insulin as a model drug, demonstrated that the SOMA delivers active pharmaceutical ingredient plasma levels comparable to those achieved with subcutaneous millipost administration.

  • 22.
    Abramson, Alex
    et al.
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Caffarel-Salvador, Ester
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Soares, Vance
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Minahan, Daniel
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Tian, Ryan Yu
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Lu, Xiaoya
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Dellal, David
    MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Gao, Yuan
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Kim, Soyoung
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Wainer, Jacob
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Collins, Joy
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Tamang, Siddartha
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Hayward, Alison
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Div Comparat Med, Cambridge, MA 02139 USA..
    Yoshitake, Tadayuki
    MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.;MIT, Elect Res Lab, Cambridge, MA 02139 USA..
    Lee, Hsiang-Chieh
    MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.;MIT, Elect Res Lab, Cambridge, MA 02139 USA..
    Fujimoto, James
    MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.;MIT, Elect Res Lab, Cambridge, MA 02139 USA..
    Fels, Johannes
    Global Drug Discovery, Global Res Technol, Malov, Denmark.;Novo Nordisk, Device R&D, Malov, Denmark..
    Frederiksen, Morten Revsgaard
    Global Drug Discovery, Global Res Technol, Malov, Denmark.;Novo Nordisk, Device R&D, Malov, Denmark..
    Rahbek, Ulrik
    Global Drug Discovery, Global Res Technol, Malov, Denmark.;Novo Nordisk, Device R&D, Malov, Denmark..
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Langer, Robert
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, Cambridge, MA 02139 USA.;MIT, Media Lab, Cambridge, MA 02139 USA..
    Traverso, Giovanni
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, Cambridge, MA 02139 USA.;Harvard Med Sch, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA..
    A luminal unfolding microneedle injector for oral delivery of macromolecules2019In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 25, no 10, p. 1512-+Article in journal (Refereed)
    Abstract [en]

    Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes(1,2), yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications(3-5). Compared with subcutaneously administered drugs, oral formulations create less patient discomfort(4), show greater chemical stability at high temperatures(6), and do not generate biohazardous needle waste(7). An oral dosage form for biologic medications is ideal; however, macromolecule drugs are not readily absorbed into the bloodstream through the gastrointestinal tract(8). We developed an ingestible capsule, termed the luminal unfolding microneedle injector, which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms. During ex vivo human and in vivo swine studies, the device consistently delivered the microneedles to the tissue without causing complete thickness perforations. Using insulin as a model drug, we showed that, when actuated, the luminal unfolding microneedle injector provided a faster pharmacokinetic uptake profile and a systemic uptake > 10% of that of a subcutaneous injection over a 4-h sampling period. With the ability to load a multitude of microneedle formulations, the device can serve as a platform to orally deliver therapeutic doses of macromolecule drugs.

  • 23.
    Abramson, Alex
    et al.
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Stanford Univ, 443 Via Ortega, Stanford, CA 94305 USA..
    Dellal, David
    MIT, Dept Mech Engn, Cambridge, MA 02139 USA.;Yale Univ, 333 Cedar St, New Haven, CT 06510 USA..
    Kong, Yong Lin
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Univ Utah, Dept Mech Engn, Salt Lake City, UT 84112 USA..
    Zhou, Jianlin
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Cornell Univ, Phillips Hall,106 Hoy Rd, Ithaca, NY 14853 USA..
    Gao, Yuan
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Collins, Joy
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Tamang, Siddartha
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Wainer, Jacob
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Fractyl Labs Inc, 17 Hartwell Ave, Lexington, MA 02421 USA..
    McManus, Rebecca
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Hayward, Alison
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Div Comparat Med, Cambridge, MA 02139 USA..
    Frederiksen, Morten Revsgaard
    Novo Nordisk AS, Global Res Technol & Device R&D, Malov, Denmark..
    Water, Jorrit J.
    Novo Nordisk AS, Global Res Technol & Device R&D, Malov, Denmark..
    Jensen, Brian
    Novo Nordisk AS, Global Res Technol & Device R&D, Malov, Denmark..
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Langer, Robert
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, Cambridge, MA 02139 USA..
    Traverso, Giovanni
    MIT, Dept Chem Engn, Cambridge, MA 02139 USA.;MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;MIT, Dept Mech Engn, Cambridge, MA 02139 USA.;Harvard Med Sch, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA..
    Ingestible transiently anchoring electronics for microstimulation and conductive signaling2020In: Science Advances, E-ISSN 2375-2548, Vol. 6, no 35, article id eaaz0127Article in journal (Refereed)
    Abstract [en]

    Ingestible electronic devices enable noninvasive evaluation and diagnosis of pathologies in the gastrointestinal (GI) tract but generally cannot therapeutically interact with the tissue wall. Here, we report the development of an orally administered electrical stimulation device characterized in ex vivo human tissue and in in vivo swine models, which transiently anchored itself to the stomach by autonomously inserting electrically conductive, hooked probes. The probes provided stimulation to the tissue via timed electrical pulses that could be used as a treatment for gastric motility disorders. To demonstrate interaction with stomach muscle tissue, we used the electrical stimulation to induce acute muscular contractions. Pulses conductively signaled the probes' successful anchoring and detachment events to a parenterally placed device. The ability to anchor into and electrically interact with targeted GI tissues controlled by the enteric nervous system introduces opportunities to treat a multitude of associated pathologies.

  • 24. Abramson, Alex
    et al.
    Frederiksen, Morten Revsgaard
    Vegge, Andreas
    Jensen, Brian
    Poulsen, Mette
    Mouridsen, Brian
    Jespersen, Mikkel Oliver
    Kirk, Rikke Kaae
    Windum, Jesper
    Hubálek, František
    Water, Jorrit J.
    Fels, Johannes
    Gunnarsson, Stefán B.
    Bohr, Adam
    Straarup, Ellen Marie
    Ley, Mikkel Wennemoes Hvitfeld
    Lu, Xiaoya
    Wainer, Jacob
    Collins, Joy
    Tamang, Siddartha
    Ishida, Keiko
    Hayward, Alison
    Herskind, Peter
    Buckley, Stephen T.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA; MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
    Langer, Robert
    Rahbek, Ulrik
    Traverso, Giovanni
    Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors2021In: Nature Biotechnology, ISSN 1087-0156, E-ISSN 1546-1696, Vol. 40, no 1, p. 103-109Article in journal (Refereed)
    Abstract [en]

    Oral administration provides a simple and non-invasive approach for drug delivery. However, due to poor absorption and swift enzymatic degradation in the gastrointestinal tract, a wide range of molecules must be parenterally injected to attain required doses and pharmacokinetics. Here we present an orally dosed liquid auto-injector capable of delivering up to 4-mg doses of a bioavailable drug with the rapid pharmacokinetics of an injection, reaching an absolute bioavailability of up to 80% and a maximum plasma drug concentration within 30 min after dosing. This approach improves dosing efficiencies and pharmacokinetics an order of magnitude over our previously designed injector capsules and up to two orders of magnitude over clinically available and preclinical chemical permeation enhancement technologies. We administered the capsules to swine for delivery of clinically relevant doses of four commonly injected medications, including adalimumab, a GLP-1 analog, recombinant human insulin and epinephrine. These multi-day dosing experiments and oral administration in awake animal models support the translational potential of the system. 

  • 25.
    Abtahi, Farhad
    et al.
    KTH, School of Technology and Health (STH), Patient Safety.
    Gyllensten, Illapha Cuba
    KTH, School of Technology and Health (STH).
    Lindecrantz, Kaj
    KTH, School of Technology and Health (STH), Medical sensors, signals and systems (MSSS).
    Seoane, Fernando
    KTH, School of Technology and Health (STH), Medical sensors, signals and systems (MSSS).
    Software tool for analysis of breathing-related errors in transthoracic electrical bioimpedance spectroscopy measurements2012In: Journal of Physics, Conference Series, ISSN 1742-6588, E-ISSN 1742-6596, Vol. 407, no 1, p. 012028-Article in journal (Refereed)
    Abstract [en]

    During the last decades, Electrical Bioimpedance Spectroscopy (EBIS) has been applied in a range of different applications and mainly using the frequency sweep-technique. Traditionally the tissue under study is considered to be timeinvariant and dynamic changes of tissue activity are ignored and instead treated as a noise source. This assumption has not been adequately tested and could have a negative impact and limit the accuracy for impedance monitoring systems. In order to successfully use frequency-sweeping EBIS for monitoring time-variant systems, it is paramount to study the effect of frequency-sweep delay on Cole Model-based analysis. In this work, we present a software tool that can be used to simulate the influence of respiration activity in frequency-sweep EBIS measurements of the human thorax and analyse the effects of the different error sources. Preliminary results indicate that the deviation on the EBIS measurement might be significant at any frequency, and especially in the impedance plane. Therefore the impact on Cole-model analysis might be different depending on method applied for Cole parameter estimation.

  • 26.
    Abtahi, Jahan
    et al.
    Linköping Univ, Dept Oral & Maxillofacial Surg, Linköping, Sweden.;Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden.;Linköping Univ, Ctr Med Image Sci & Visualizat CMIV, Linköping, Sweden..
    Klintström, Benjamin
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.
    Klintström, Eva
    Linköping Univ, Ctr Med Image Sci & Visualizat CMIV, Linköping, Sweden.;Linköping Univ, Dept Radiol, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Ibandronate Reduces the Surface Bone Resorption of Mandibular Bone Grafts: A Randomized Trial With Internal Controls2021In: JBMR Plus, ISSN 2473-4039, Vol. 5, no 3, article id e10468Article in journal (Refereed)
    Abstract [en]

    Autologous bone grafts are considered the gold standard for reconstruction of the edentulous alveolar ridges. However, this procedure is associated with unpredictable bone loss caused by physiological bone resorption. Bisphosphonates are antiresorptive drugs that act specifically on osteoclasts, thereby maintaining bone density, volume, and strength. It was hypothesized that the resorption of bone grafts treated with an ibandronate solution would be less advanced than bone grafts treated with saline. Ten patients who underwent bilateral sagittal split osteotomy were included in a randomized double-blind trial with internal controls. Each patient received a bone graft treated with a solution of ibandronate on one side and a graft treated with saline (controls) contralaterally. Radiographs for the measurement of bone volume were obtained at 2 weeks and at 6 months after surgery. The primary endpoint was the difference in the change of bone volume between the control and the ibandronate bone grafts 6 months after surgery. All of the bone grafts healed without complications. One patient was excluded because of reoperation. In eight of the nine patients, the ibandronate bone grafts showed an increase in bone volume compared with baseline, with an average gain of 126 mm(3) (40% more than baseline) with a range of +27 to +218 mm(3). Only one ibandronate-treated graft had a decrease in bone volume (8%). In the controls, an average bone volume loss of -146 mm(3) (58% of baseline) with a range of -29 to -301 mm(3) was seen. In the maxillofacial field, the reconstructions of atrophic alveolar ridges, especially in the esthetical zones, are challenging. These results show that bone grafts locally treated with ibandronate solution increases the remaining bone volume. This might lead to new possibilities for the maxillofacial surgeons in the preservation of bone graft volumes and for dental implant installations.

  • 27. Acero Sanchez, Josep Ll.
    et al.
    Joda, Hamdi
    Henry, Olivier Y. F.
    Solnestam, Beata W.
    Kvastad, Linda
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sahlén, Pelin
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Laddach, Nadja
    Ramakrishnan, Dheeraj
    Riley, Ian
    Schwind, Carmen
    Latta, Daniel
    O'Sullivan, Ciara K.
    Electrochemical Genetic Profiling of Single Cancer Cells2017In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 89, no 6, p. 3378-3385Article in journal (Refereed)
    Abstract [en]

    Recent understandings in the development and spread of cancer have led to the realization of novel single cell analysis platforms focused on circulating tumor cells (CTCs). A simple, rapid, and inexpensive analytical platform capable of providing genetic information on these rare cells is highly desirable to support clinicians and researchers alike to either support the selection or adjustment of therapy or provide fundamental insights into cell function and cancer progression mechanisms. We report on the genetic profiling of single cancer cells, exploiting a combination of multiplex ligation-dependent probe amplification (MLPA) and electrochemical detection. Cells were isolated using laser capture and lysed, and the mRNA was extracted and transcribed into DNA. Seven markers were amplified by MLPA, which allows for the simultaneous amplification of multiple targets with a single primer pair, using MLPA probes containing unique barcode sequences. Capture probes complementary to each of these barcode sequences were immobilized on a printed circuit board (PCB) manufactured electrode array and exposed to single-stranded MLPA products and subsequently to a single stranded DNA reporter probe bearing a HRP molecule, followed by substrate addition and fast electrochemical pulse amperometric detection. We present asimple, rapid, flexible, and inexpensive approach for the simultaneous quantification of multiple breast cancer related mRNA markers, with single tumor cell sensitivity.

  • 28.
    Acharjee, Animesh
    et al.
    Univ Birmingham, Coll Med & Dent Sci, Inst Canc & Genom Sci, Birmingham B15 2TT, W Midlands, England.;Fdn Trust, Univ Hosp Birmingham NHS, Inst Translat Med, Birmingham B15 2TT, W Midlands, England.;Univ Hosp Birmingham, NIHR Surg Reconstruct & Microbiol Res Ctr, Birmingham B15 2WB, W Midlands, England..
    Agarwal, Prasoon
    KTH, School of Electrical Engineering and Computer Science (EECS), Computer Science, Computational Science and Technology (CST).
    Nash, Katrina
    Univ Birmingham, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England..
    Bano, Subia
    Elvesys Microfluid Innovat Ctr, F-75011 Paris, France..
    Rahmans, Taufiq
    Univ Cambridge, Dept Pharmacol, Tennis Court Rd, Cambridge CB2 1PD, England..
    Gkoutos, Georgios, V
    Univ Birmingham, Coll Med & Dent Sci, Inst Canc & Genom Sci, Birmingham B15 2TT, W Midlands, England.;Fdn Trust, Univ Hosp Birmingham NHS, Inst Translat Med, Birmingham B15 2TT, W Midlands, England.;Univ Hosp Birmingham, NIHR Surg Reconstruct & Microbiol Res Ctr, Birmingham B15 2WB, W Midlands, England.;MRC Hlth Data Res UK HDR UK, London, England.;NIHR Expt Canc Med Ctr, Birmingham B15 2TT, W Midlands, England.;Univ Hosp Birmingham, NIHR Biomed Res Ctr, Birmingham B15 2TT, W Midlands, England..
    Immune infiltration and prognostic and diagnostic use of LGALS4 in colon adenocarcinoma and bladder urothelial carcinoma2021In: American Journal of Translational Research, E-ISSN 1943-8141, Vol. 13, no 10, p. 11353-11363Article in journal (Refereed)
    Abstract [en]

    Colon adenocarcinoma (COAD) is a common tumor of the gastrointestinal tract with a high mortality rate. Current research has identified many genes associated with immune infiltration that play a vital role in the development of COAD. In this study, we analysed the prognostic and diagnostic features of such immune-related genes in the context of colonic adenocarcinoma (COAD). We analysed 17 overlapping gene expression profiles of COAD and healthy samples obtained from TCGA-COAD and public single-cell sequencing resources, to identify potential therapeutic COAD targets. We evaluated the abundance of immune infiltration with those genes using the TIMER (Tumor Immune Estimation Resource) deconvolution method. Subsequently, we developed predictive and survival models to assess the prognostic value of these genes. The LGALS4 (Galectin-4) gene was found to be significantly (P<0.05) downregulated in COAD and bladder urothelial carcinoma (BLCA) compared to healthy samples. We identified LGALS4 as a prognostic and diagnostic marker for multiple cancer types, including COAD and BLCA. Our analysis reveals a series of novel candidate drug targets, as well as candidate molecular markers, that may explain the pathogenesis of COAD and BLCA. LGALS4 gene is associated with multiple cancer types and is a possible prognostic, as well as diagnostic, marker of COAD and BLCA.

  • 29.
    Acosta, Adam Miguel
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Enzymatic breakdown of rejected wastes from the beer industry by utilising lytic polysaccharidemonooxygenases (LPMOs)2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The continued usage of fossil fuels and non-renewable materials is a key issue in modern economies. To increase the share of sustainable energy sources, bio-based approaches are inevitable. Biofuels have long been a target of the scientific community to replace fossil fuels, however, there is still ongoing research to make them a sustainable alternative. First generation biofuels use so-called energy crops to function as a biomass source for ethanol production. As energy crops would compete for land usage with food crops, first generation biofuels have sparked serious social debate, and are considered to be commercially unviable. However, second generation biofuels solve the above problem by utilising low-value by-products, primarily agricultural waste as a source for biomass.

     

    The beer industry, during the production of fermented beverages, produces massive amounts of by-products, the most abundant being brewer’s spent grain (BSG). During the beer brewing process, after the endosperm of the malted barley is hydrolysed, the resulting solid material is what the industry calls the BSG. This by-product practically consists of the barley bran, which is typically either sold as low-cost animal feed or is disposed of as trash. However, considering the vast amounts of BSG produced by large industrial actors, it poses a great potential as it is mostly lignocellulosic material, and it could be valorised into added-value products, most prominently biofuel by a biorefinery approach.

     

    Historically, glycoside hydrolases have been used to break down recalcitrant lignocellulosic biomass in biorefineries. Lytic polysaccharide monooxygenases (LPMOs) are a novel enzyme class that can induce oxidative cleavage at any distance from the end of the polysaccharide chain. LPMOs represent a great potential in boosting the activity of glycoside hydrolases when used in enzyme cocktails in biorefineries by providing additional chain ends for them to act on. The bacterial LPMO CmAA10 acts on cellulose microfibrils, and its gene was expressed in E. coli for this study. The periplasmic fraction of the microorganism was extracted, purified and identified as CmAA10. With the aid of LPMOs in applying an enzyme cocktail biorefinery approach to BSG, it is hoped to saccharify the cellulosic material and eventually contribute to a future bio-based circular economy.

  • 30. Adams, Taylor
    et al.
    Andrusivova, Zaneta
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Bergenstråhle, Joseph
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Bergenstråhle, Ludvig
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Larsson, Ludvig
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ziegler, Carly
    et al.,
    Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics2021In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170XArticle in journal (Refereed)
    Abstract [en]

    Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.

    An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.

  • 31. Adiels, Martin
    et al.
    Mardinoglu, Adil
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Chalmers University of Technology, Sweden.
    Taskinen, Marja-Riitta
    Boren, Jan
    Kinetic Studies to Elucidate Impaired Metabolism of Triglyceride-rich Lipoproteins in Humans2015In: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 6, article id 342Article, review/survey (Refereed)
    Abstract [en]

    To develop novel strategies for prevention and treatment of dyslipidemia, it is essential to understand the pathophysiology of dyslipoproteinemia in humans. Lipoprotein metabolism is a complex system in which abnormal concentrations of various lipoprotein particles can result from alterations in their rates of production, conversion, and/or catabolism. Traditional methods that measure plasma lipoprotein concentrations only provide static estimates of lipoprotein metabolism and hence limited mechanistic information. By contrast, the use of tracers labeled with stable isotopes and mathematical modeling, provides us with a powerful tool for probing lipid and lipoprotein kinetics in vivo and furthering our understanding of the pathogenesis of dyslipoproteinemia.

  • 32.
    Adolphson, Katja
    et al.
    Karolinska Inst, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Honore, Antoine
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Information Science and Engineering. Karolinska Inst, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Forsberg, David
    Karolinska Inst, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Stålhammar, Alexander Mildalen
    Karolinska Inst, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Jost, Kerstin
    Karolinska Inst, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Herlenius, Eric
    Karolinska Inst, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden..
    Predicting acute adverse events in neonates using automated vital sign pattern analysis2021In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 90, no SUPPL 1, p. 22-22Article in journal (Other academic)
  • 33. Adori, Csaba
    et al.
    Barde, Swapnali
    Bogdanovic, Nenad
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Institutet, Sweden.
    Reinscheid, Rainer R.
    Kovacs, Gabor G.
    Hokfelt, Tomas
    Neuropeptide S- and Neuropeptide S receptor-expressing neuron populations in the human pons2015In: Frontiers in Neuroanatomy, E-ISSN 1662-5129, Vol. 9Article in journal (Refereed)
    Abstract [en]

    Neuropeptide S (NPS) is a regulatory peptide with potent pharmacological effects. In rodents, NPS is expressed in a few pontine cell clusters. Its receptor (NPSR1) is, however, widely distributed in the brain. The anxiolytic and arousal promoting effects of NPS make the NPS NPSR1 system an interesting potential drug target in mood-related disorders. However, so far possible disease-related mechanisms involving NPS have only been studied in rodents. To validate the relevance of these animal studies for i.a. drug development, we have explored the distribution of NPS-expressing neurons in the human pons using in situ hybridization and stereological methods and we compared the distribution of NPS mRNA expressing neurons in the human and rat brain. The calculation revealed a total number of 22,317 +/- 2411 NPS mRNA-positive neurons in human, bilaterally. The majority of cells (84%) were located in the parabrachial area in human: in the extension of the medial and lateral parabrachial nuclei, in the Kolliker-Fuse nucleus and around the adjacent lateral lemniscus. In human, in sharp contrast to the rodents, only very few NPS-positive cells (5%) were found close to the locus coeruleus. In addition, we identified a smaller cell cluster (11% of all NPS cells) in the pontine central gray matter both in human and rat, which has not been described previously even in rodents. We also examined the distribution of NPSR1 mRNA-expressing neurons in the human pons. These cells were mainly located in the rostral laterodorsal tegmental nucleus, the cuneiform nucleus, the microcellular tegmental nucleus region and in the periaqueductal gray. Our results show that both NPS and NPSR1 in the human pons are preferentially localized in regions of importance for integration of visceral autonomic information and emotional behavior. The reported interspecies differences must, however, be considered when looking for targets for new pharmacotherapeutical interventions.

  • 34.
    Adori, Csaba
    et al.
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Daraio, Teresa
    Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Dept Mol Med & Surg, S-17176 Stockholm, Sweden..
    Kuiper, Raoul
    Karolinska Inst, Dept Lab Med, S-17177 Stockholm, Sweden..
    Barde, Swapnali
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Horvathova, Lubica
    Slovak Acad Sci, Biomed Res Ctr, Inst Expt Endocrinol, Bratislava, Slovakia..
    Yoshitake, Takashi
    Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden..
    Ihnatko, Robert
    Linköping Univ, Dept Clin Chem, S-58285 Linköping, Sweden.;Linköping Univ, Dept Clin & Expt Med, S-58285 Linköping, Sweden.;Georg August Univ Gottingen, Univ Med Ctr, Inst Pathol, Gottingen, Germany..
    Valladolid-Acebes, Ismael
    Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Dept Mol Med & Surg, S-17176 Stockholm, Sweden..
    Vercruysse, Pauline
    Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Dept Mol Med & Surg, S-17176 Stockholm, Sweden..
    Wellendorf, Ashley M.
    Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA..
    Gramignoli, Roberto
    Karolinska Inst, Dept Lab Med, S-17177 Stockholm, Sweden..
    Bozoky, Bela
    Karolinska Univ Hosp, Dept Clin Pathol Cytol, Huddinge, Sweden..
    Kehr, Jan
    Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden..
    Theodorsson, Elvar
    Linköping Univ, Dept Clin Chem, S-58285 Linköping, Sweden.;Linköping Univ, Dept Clin & Expt Med, S-58285 Linköping, Sweden..
    Cancelas, Jose A.
    Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.;Univ Cincinnati, Hoxworth Blood Ctr, Coll Med, Cincinnati, OH 45267 USA..
    Mravec, Boris
    Slovak Acad Sci, Biomed Res Ctr, Inst Expt Endocrinol, Bratislava, Slovakia.;Comenius Univ, Fac Med, Inst Physiol, Bratislava, Slovakia..
    Jorns, Carl
    Karolinska Univ Hosp Huddinge, PO Transplantat, S-14152 Stockholm, Sweden..
    Ellis, Ewa
    Karolinska Inst, Karolinska Univ Hosp, Dept Transplantat Surg, S-17177 Stockholm, Sweden.;Karolinska Inst, Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol CLINTEC, S-17177 Stockholm, Sweden..
    Mulder, Jan
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.;Royal Inst Technol, Sci Life Lab, S-10691 Stockholm, Sweden..
    Bark, Christina
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Hokfelt, Tomas
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Disorganization and degeneration of liver sympathetic innervations in nonalcoholic fatty liver disease revealed by 3D imaging2021In: Science Advances, E-ISSN 2375-2548, Vol. 7, no 30, article id eabg5733Article in journal (Refereed)
    Abstract [en]

    Hepatic nerves have a complex role in synchronizing liver metabolism. Here, we used three-dimensional (3D) immunoimaging to explore the integrity of the hepatic nervous system in experimental and human nonalcoholic fatty liver disease (NAFLD). We demonstrate parallel signs of mild degeneration and axonal sprouting of sympathetic innervations in early stages of experimental NAFLD and a collapse of sympathetic arborization in steatohepatitis. Human fatty livers display a similar pattern of sympathetic nerve degeneration, correlating with the severity of NAFLD pathology. We show that chronic sympathetic hyperexcitation is a key factor in the axonal degeneration, here genetically phenocopied in mice deficient of the Rac-1 activator Vav3. In experimental steatohepatitis, 3D imaging reveals a severe portal vein contraction, spatially correlated with the extension of the remaining nerves around the portal vein, enlightening a potential intrahepatic neuronal mechanism of portal hypertension. These fundamental alterations in liver innervation and vasculature uncover previously unidentified neuronal components in NAFLD pathomechanisms.

  • 35. Adori, Csaba
    et al.
    Glueck, Laura
    Barde, Swapnali
    Yoshitake, Takashi
    Kovacs, Gabor G.
    Mulder, Jan
    Magloczky, Zsofia
    Havas, Laszlo
    Boelcskei, Kata
    Mitsios, Nicholas
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Szolcsanyi, Janos
    Kehr, Jan
    Ronnback, Annica
    Schwartz, Thue
    Rehfeld, Jens F.
    Harkany, Tibor
    Palkovits, Miklos
    Schulz, Stefan
    Hokfelt, Tomas
    Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system: new aspects on Alzheimer's disease2015In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 129, no 4, p. 541-563Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites. This is noteworthy since cortical and hypothalamic somatostatin content is reduced in neurodegenerative pathologies. Yet a possible role of a somatostatin signal deficit in the maintenance of noradrenergic projections remains unknown. Here, we deployed tissue microarrays, immunohistochemistry, quantitative morphometry and mRNA profiling in a cohort of Alzheimer's and age-matched control brains in combination with genetic models of somatostatin receptor deficiency to establish causality between defunct somatostatin signalling and noradrenergic neurodegeneration. In Alzheimer's disease, we found significantly reduced somatostatin protein expression in the temporal cortex, with aberrant clustering and bulging of tyrosine hydroxylase-immunoreactive afferents. As such, somatostatin receptor 2 (SSTR2) mRNA was highly expressed in the human LC, with its levels significantly decreasing from Braak stages III/IV and onwards, i.e., a process preceding advanced Alzheimer's pathology. The loss of SSTR2 transcripts in the LC neurons appeared selective, since tyrosine hydroxylase, dopamine beta-hydroxylase, galanin or galanin receptor 3 mRNAs remained unchanged. We modeled these pathogenic changes in Sstr2 (-/-) mice and, unlike in Sstr1 (-/-) or Sstr4 (-/-) genotypes, they showed selective, global and progressive degeneration of their central noradrenergic projections. However, neuronal perikarya in the LC were found intact until late adulthood (< 8 months) in Sstr2 (-/-) mice. In contrast, the noradrenergic neurons in the superior cervical ganglion lacked SSTR2 and, as expected, the sympathetic innervation of the head region did not show any signs of degeneration. Our results indicate that SSTR2-mediated signaling is integral to the maintenance of central noradrenergic projections at the system level, and that early loss of somatostatin receptor 2 function may be associated with the selective vulnerability of the noradrenergic system in Alzheimer's disease.

  • 36.
    Adori, Monika
    et al.
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Bhat, Sadam
    Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
    Gramignoli, Roberto
    Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Valladolid-Acebes, Ismael
    Department of Molecular Medicine and Surgery, The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
    Bengtsson, Tore
    Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), Stockholm University, Stockholm, Sweden.
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Adori, Csaba
    Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), Stockholm University, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hepatic Innervations and Nonalcoholic Fatty Liver Disease2023In: Seminars in liver disease (Print), ISSN 0272-8087, E-ISSN 1098-8971, Vol. 43, no 2, p. 149-162Article in journal (Refereed)
    Abstract [en]

    Abbreviations: VMN/PVN, hypothalamic ventromedial nucleus/paraventricular nucleus; VLM/VMM, ventrolateral medulla/ventromedial medulla; SMG/CG, superior mesenteric ganglion/caeliac ganglia; NTS, nucleus of the solitary tract; NG, nodose ganglion. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. Increased sympathetic (noradrenergic) nerve tone has a complex role in the etiopathomechanism of NAFLD, affecting the development/progression of steatosis, inflammation, fibrosis, and liver hemodynamical alterations. Also, lipid sensing by vagal afferent fibers is an important player in the development of hepatic steatosis. Moreover, disorganization and progressive degeneration of liver sympathetic nerves were recently described in human and experimental NAFLD. These structural alterations likely come along with impaired liver sympathetic nerve functionality and lack of adequate hepatic noradrenergic signaling. Here, we first overview the anatomy and physiology of liver nerves. Then, we discuss the nerve impairments in NAFLD and their pathophysiological consequences in hepatic metabolism, inflammation, fibrosis, and hemodynamics. We conclude that further studies considering the spatial-temporal dynamics of structural and functional changes in the hepatic nervous system may lead to more targeted pharmacotherapeutic advances in NAFLD.

  • 37. Affatato, S.
    et al.
    Leardini, W.
    Jedenmalm, Anneli
    KTH, School of Industrial Engineering and Management (ITM), Materials Science and Engineering.
    Ruggeri, O.
    Toni, A.
    Larger diameter bearings reduce wear in metal-on-metal hip implants2007In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, no 456, p. 153-158Article in journal (Refereed)
    Abstract [en]

    Metal-on-metal hip arthroplasty has the longest clinical history of all total arthroplasties. We asked whether large diameter femoral heads would result in less wear than those with small diameters. We also asked if there is a threshold diameter that ensures good wear behavior. We tested three batches of cast high-carbon cobalt-chromium-molybdenum hip implants (28 mm, 36 min, and 54 min diameters) in a hip simulator for 5 million cycles. We used bovine serum as lubricant and weighed the samples at regular intervals during testing. The 28-mm configuration had almost twice the wear of the 54-mm configuration, but we observed no difference between the 36-mm and the 54-mm configurations. The similarity in the wear performances of the larger configurations supports the presence of a threshold diameter that ensures good wear behavior.

  • 38.
    Agasteen Anantharaj, Kingsly Anand
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Improving management of patient flow at Radiology Department using Simulation Models2021Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The Swedish healthcare system is considered to have good healthcare productivity and efficiency with moderate cost but seems to have some future challenges. Sweden is moving towards the aging population as it requires development in medical care techniques and technologies to provide care to elderly patients. This increases the pressure on the healthcare system. Hence, the number of patients in the hospital increase, as a result, the flow of patients within the wards are increased. Furthermore, the pandemic has increased the number of people admitted to hospitals. As a consequence, even for high-priority cases, the wait times are rising.

    The Skaraborg Hospital Group, SHG, and other general hospitals, in particular, are focusing on how to handle patient flow at various levels within departments and clinics by improving patient flow quality. Production and capacity preparation (PCP) is a commonly used industry tool for resolving bottlenecks. Hence, this method needs to be adopted within the hospital and by the healthcare sector to a larger extent.

    Since many patients from different specialty departments use the Radiology department's facilities, it is often a "bottleneck" in inpatient traffic at hospitals. Furthermore, the influx of patients with covid-19 has increased the department's workload.

    This master's thesis aims to assist the Radiology department in improving their production and capacity planning to increase unit flow performance. The project involves supporting key staff in the department in estimating demand to align different patient movements with equipment and personnel services. Improving radiology department flow efficiency can lead to more even and healthy patient flows around the hospital, reducing "buffers" of patients and longer stays at different specialist clinics.

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  • 39. Agathokleous, E.
    et al.
    Barceló, D.
    Aschner, M.
    Azevedo, R. A.
    Bhattacharya, Prosun
    KTH, School of Architecture and the Built Environment (ABE), Sustainable development, Environmental science and Engineering, Water and Environmental Engineering.
    Costantini, D.
    Cutler, G. C.
    De Marco, A.
    Docea, A. O.
    Dórea, J. G.
    Duke, S. O.
    Efferth, T.
    Fatta-Kassinos, D.
    Fotopoulos, V.
    Ginebreda, A.
    Guedes, R. N. C.
    Hayes, A. W.
    Iavicoli, I.
    Kalantzi, O. -I
    Koike, T.
    Kouretas, D.
    Kumar, M.
    Manautou, J. E.
    Moore, M. N.
    Paoletti, E.
    Peñuelas, J.
    Picó, Y.
    Reiter, R. J.
    Rezaee, R.
    Rinklebe, J.
    Rocha-Santos, T.
    Sicard, P.
    Sonne, C.
    Teaf, C.
    Tsatsakis, A.
    Vardavas, A. I.
    Wang, W.
    Zeng, E. Y.
    Calabrese, E. J.
    Rethinking Subthreshold Effects in Regulatory Chemical Risk Assessments2022In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 56, no 16, p. 11095-11099Article in journal (Refereed)
  • 40.
    Aghanoori, Mohamad-Reza
    et al.
    St Boniface Gen Hosp, Albrechtsen Res Ctr, Div Neurodegenerat Disorders, Winnipeg, MB, Canada.;Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada.;Univ Calgary, Cumming Sch Med, Dept Med Genet, 3330 Hosp Dr NW, Calgary, AB T2N 4N2, Canada..
    Agarwal, Prasoon
    KTH, School of Electrical Engineering and Computer Science (EECS), Computer Science, Computational Science and Technology (CST). Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada.;Univ Manitoba, Childrens Hosp Res Inst Manitoba, Winnipeg, MB, Canada..
    Gauvin, Evan
    St Boniface Gen Hosp, Albrechtsen Res Ctr, Div Neurodegenerat Disorders, Winnipeg, MB, Canada..
    Nagalingam, Raghu S.
    Univ Manitoba, Rady Fac Hlth Sci, Dept Physiol & Pathophysiol, Winnipeg, MB, Canada.;St Boniface Gen Hosp, Inst Cardiovasc Sci, Albrechtsen Res Ctr, Winnipeg, MB, Canada..
    Bonomo, Raiza
    Loyola Univ, Cellular & Mol Dept, Stritch Sch Med, Chicago, IL 60611 USA..
    Yathindranath, Vinith
    Univ Manitoba, Kleysen Inst Adv Med, Winnipeg, MB, Canada..
    Smith, Darrell R.
    St Boniface Gen Hosp, Albrechtsen Res Ctr, Div Neurodegenerat Disorders, Winnipeg, MB, Canada..
    Hai, Yan
    Univ Manitoba, Rady Fac Hlth Sci, Dept Biochem & Med Genet, Winnipeg, MB, Canada..
    Lee, Samantha
    Univ Manitoba, Rady Fac Hlth Sci, Dept Biochem & Med Genet, Winnipeg, MB, Canada..
    Jolivalt, Corinne G.
    Univ Calif San Diego, Dept Pathol, San Diego, CA USA..
    Calcutt, Nigel A.
    Univ Calif San Diego, Dept Pathol, San Diego, CA USA..
    Jones, Meaghan J.
    Univ Manitoba, Rady Fac Hlth Sci, Dept Biochem & Med Genet, Winnipeg, MB, Canada..
    Czubryt, Michael P.
    Univ Manitoba, Rady Fac Hlth Sci, Dept Physiol & Pathophysiol, Winnipeg, MB, Canada.;St Boniface Gen Hosp, Inst Cardiovasc Sci, Albrechtsen Res Ctr, Winnipeg, MB, Canada..
    Miller, Donald W.
    Univ Manitoba, Kleysen Inst Adv Med, Winnipeg, MB, Canada..
    Dolinsky, Vernon W.
    Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada.;Univ Manitoba, Childrens Hosp Res Inst Manitoba, Winnipeg, MB, Canada..
    Mansuy-Aubert, Virginie
    Loyola Univ, Cellular & Mol Dept, Stritch Sch Med, Chicago, IL 60611 USA..
    Fernyhough, Paul
    St Boniface Gen Hosp, Albrechtsen Res Ctr, Div Neurodegenerat Disorders, Winnipeg, MB, Canada.;Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada..
    CEBP beta regulation of endogenous IGF-1 in adult sensory neurons can be mobilized to overcome diabetes-induced deficits in bioenergetics and axonal outgrowth2022In: Cellular and Molecular Life Sciences (CMLS), ISSN 1420-682X, E-ISSN 1420-9071, Vol. 79, no 4, article id 193Article in journal (Refereed)
    Abstract [en]

    Aberrant insulin-like growth factor 1 (IGF-1) signaling has been proposed as a contributing factor to the development of neurodegenerative disorders including diabetic neuropathy, and delivery of exogenous IGF-1 has been explored as a treatment for Alzheimer's disease and amyotrophic lateral sclerosis. However, the role of autocrine/paracrine IGF-1 in neuroprotection has not been well established. We therefore used in vitro cell culture systems and animal models of diabetic neuropathy to characterize endogenous IGF-1 in sensory neurons and determine the factors regulating IGF-1 expression and/or affecting neuronal health. Single-cell RNA sequencing (scRNA-Seq) and in situ hybridization analyses revealed high expression of endogenous IGF-1 in non-peptidergic neurons and satellite glial cells (SGCs) of dorsal root ganglia (DRG). Brain cortex and DRG had higher IGF-1 gene expression than sciatic nerve. Bidirectional transport of IGF-1 along sensory nerves was observed. Despite no difference in IGF-1 receptor levels, IGF-1 gene expression was significantly (P < 0.05) reduced in liver and DRG from streptozotocin (STZ)-induced type 1 diabetic rats, Zucker diabetic fatty (ZDF) rats, mice on a high-fat/ high-sugar diet and db/db type 2 diabetic mice. Hyperglycemia suppressed IGF-1 gene expression in cultured DRG neurons and this was reversed by exogenous IGF-1 or the aldose reductase inhibitor sorbinil. Transcription factors, such as NFAT1 and CEBP beta, were also less enriched at the IGF-1 promoter in DRG from diabetic rats vs control rats. CEBP beta overexpression promoted neurite outgrowth and mitochondrial respiration, both of which were blunted by knocking down or blocking IGF-1. Suppression of endogenous IGF-1 in diabetes may contribute to neuropathy and its upregulation at the transcriptional level by CEBP beta can be a promising therapeutic approach.

  • 41.
    Aghdam, Rosa
    et al.
    Inst Res Fundamental Sci IPM, Sch Biol Sci, Tehran, Iran..
    Habibi, Mahnaz
    Islamic Azad Univ, Dept Math, Qazvin Branch, Qazvin, Iran..
    Taheri, Golnaz
    KTH, School of Electrical Engineering and Computer Science (EECS), Computer Science, Computational Science and Technology (CST). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Using informative features in machine learning based method for COVID-19 drug repurposing2021In: Journal of Cheminformatics, E-ISSN 1758-2946, Vol. 13, no 1, article id 70Article in journal (Refereed)
    Abstract [en]

    Coronavirus disease 2019 (COVID-19) is caused by a novel virus named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This virus induced a large number of deaths and millions of confirmed cases worldwide, creating a serious danger to public health. However, there are no specific therapies or drugs available for COVID-19 treatment. While new drug discovery is a long process, repurposing available drugs for COVID-19 can help recognize treatments with known clinical profiles. Computational drug repurposing methods can reduce the cost, time, and risk of drug toxicity. In this work, we build a graph as a COVID-19 related biological network. This network is related to virus targets or their associated biological processes. We select essential proteins in the constructed biological network that lead to a major disruption in the network. Our method from these essential proteins chooses 93 proteins related to COVID-19 pathology. Then, we propose multiple informative features based on drug-target and protein-protein interaction information. Through these informative features, we find five appropriate clusters of drugs that contain some candidates as potential COVID-19 treatments. To evaluate our results, we provide statistical and clinical evidence for our candidate drugs. From our proposed candidate drugs, 80% of them were studied in other studies and clinical trials.

  • 42. Agres, Kat Rose
    et al.
    Schaefer, Rebecca
    Volk, Anja
    van Hooren, Susan
    Holzapfel, Andre
    KTH, School of Electrical Engineering and Computer Science (EECS), Human Centered Technology, Media Technology and Interaction Design, MID.
    Dalla Bella, Simone
    Mueller, Meinard
    de Witte, Martina
    Herremans, Dorien
    Ramirez Melendez, Rafael
    Neerincx, Mark A.
    Ruiz, Sebastian
    Meredith, David
    Dimitriadis, Theo
    Magee, Wendy L.
    Music, Computing, and Health: A roadmap for the current and future roles of music technology for health care and well-being2021Manuscript (preprint) (Other academic)
  • 43.
    Aguet, Francois
    et al.
    Illumina Inc, Illumina Artificial Intelligence Lab, San Diego, CA 92122 USA..
    Alasoo, Kaur
    Univ Tartu, Inst Comp Sci, Tartu, Estonia..
    Li, Yang, I
    Univ Chicago, Dept Med, Sect Genet Med, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Battle, Alexis
    Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA.;Johns Hopkins Univ, Malone Ctr Engn Healthcare, Baltimore, MD USA.;Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA.;Johns Hopkins Univ, Dept Genet Med, Baltimore, MD USA..
    Im, Hae Kyung
    Univ Chicago, Dept Med, Sect Genet Med, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Montgomery, Stephen B.
    Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.;Stanford Univ, Dept Genet, Stanford, CA 94305 USA..
    Lappalainen, Tuuli
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH Royal Inst Technol, Dept Gene Technol, Sci Life Lab, Stockholm, Sweden.;.
    Molecular quantitative trait loci2023In: NATURE REVIEWS METHODS PRIMERS, ISSN 2662-8449, Vol. 3, no 1, article id 4Article in journal (Refereed)
    Abstract [en]

    Understanding functional effects of genetic variants is one of the key challenges in human genetics, as much of disease-associated variation is located in non-coding regions with typically unknown putative gene regulatory effects. One of the most important approaches in this field has been molecular quantitative trait locus (molQTL) mapping, where genetic variation is associated with molecular traits that can be measured at scale, such as gene expression, splicing and chromatin accessibility. The maturity of the field and large-scale studies have produced a rich set of established methods for molQTL analysis, with novel technologies opening up new areas of discovery. In this Primer, we discuss the study design, input data and statistical methods for molQTL mapping and outline the properties of the resulting data as well as popular downstream applications. We review both the limitations and caveats of molQTL mapping as well as future potential approaches to tackle them. With technological development now providing many complementary methods for functional characterization of genetic variants, we anticipate that molQTLs will remain an important part of this toolkit as the only existing approach that can measure human variation in its native genomic, cellular and tissue context.

  • 44.
    Aguilar, Antonio
    et al.
    Digital Enterprise Research Institute, National University of Ireland, Galway, Ireland.
    van der Putten, Wil
    Department of Medical Physics, University College Hospital Galway, Galway, Ireland .
    Maguire Jr., Gerald Q.
    KTH, School of Information and Communication Technology (ICT), Communication Systems, CoS, Radio Systems Laboratory (RS Lab).
    Positive Patient Identification using RFID and Wireless  Networks2006In: Proceedings of the HISI 11th Annual Conference and Scientific Symposium, Dublin, Ireland, Dublin, Ireland, 2006Conference paper (Refereed)
    Abstract [en]

    The increased focus on patient safety in hospitals has yielded a flood of new technologies and tools seeking to improve the quality of patient care at the point-of-care. Hospitals are complex institutions by nature, and are constantly challenged to improve the quality of healthcare delivered to patients while trying to reduce the rate of medical errors and improve patient safety. Here a simple mistake such as patient misidentification, specimen misidentification, wrong medication, or wrong blood transfusion can cause the loss of a patient's life. The focus of this paper is the implementation and evaluation of a handheld-based patient identification system that uses radio frequency identification (RFID) and 802.11b wireless networks to identify patients. In this approach, each patient is given a RFID wristband which contains demographic information (patient ID number, patient summary, hospital code) of the patient. A handheld device equipped with 802.11b wireless connectivity and a RFID reader is then used by the medical staff to read the patient's wristband and identify the patient. This work was carried out at the Department of Medical Physics and Bioengineering at the University College Hospital Galway, Ireland and in co-operation with the National University of Ireland, Galway.

  • 45.
    Ahlborg, Liv
    et al.
    Karolinska Institutet.
    Weurlander, Maria
    KTH, School of Education and Communication in Engineering Science (ECE), Learning.
    Hedman, Leif
    Karolinska Institutet.
    Nisell, Henry
    Karolinska Institutet.
    Lindqvist, Pelle G
    Karolinska Institutet.
    Felländer-Tsai, Li
    Karolinska Institutet.
    Enochsson, Lars
    Karolinska Institutet.
    Individualized feedback during simulated laparoscopic training: a mixed methods study2015In: International Journal of Medical Education, E-ISSN 2042-6372, Vol. 6, p. 93-100Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: This study aimed to explore the value of individualized feedback on performance, flow and self-efficacy during simulated laparoscopy. Furthermore, we wished to explore attitudes towards feedback and simulator training among medical students.

    METHODS: Sixteen medical students were included in the study and randomized to laparoscopic simulator training with or without feedback. A teacher provided individualized feedback continuously throughout the procedures to the target group. Validated questionnaires and scales were used to evaluate self-efficacy and flow. The Mann-Whitney U test was used to evaluate differences between groups regarding laparoscopic performance (instrument path length), self-efficacy and flow. Qualitative data was collected by group interviews and interpreted using inductive thematic analyses.

    RESULTS: Sixteen students completed the simulator training and questionnaires. Instrument path length was shorter in the feedback group (median 3.9 m; IQR: 3.3-4.9) as compared to the control group (median 5.9 m; IQR: 5.0-8.1), p<0.05. Self-efficacy improved in both groups. Eleven students participated in the focus interviews. Participants in the control group expressed that they had fun, whereas participants in the feedback group were more concentrated on the task and also more anxious. Both groups had high ambitions to succeed and also expressed the importance of getting feedback. The authenticity of the training scenario was important for the learning process.

    CONCLUSIONS: This study highlights the importance of individualized feedback during simulated laparoscopy training. The next step is to further optimize feedback and to transfer standardized and individualized feedback from the simulated setting to the operating room.

  • 46. Ahlstrom, L.
    et al.
    Dellve, Lotta
    KTH, School of Technology and Health (STH), Health Systems Engineering, Ergonomics. University of Borås, Sweden.
    Hagberg, M.
    Ahlberg, K.
    Women with Neck Pain on Long-Term Sick Leave — Approaches Used in the Return to Work Process: A Qualitative Study2016In: Journal of occupational rehabilitation, ISSN 1053-0487, E-ISSN 1573-3688, p. 1-14Article in journal (Refereed)
    Abstract [en]

    Purpose There are difficulties in the process of return to work (RTW) from long-term sick leave, both in general and regarding sick leave because of neck pain in particular. Neck pain is difficult to assess, problematic to rehabilitate, and hard to cure; and it is not always easy to decide whether the pain is work-related. The outcome of RTW could be dependent upon individuals’ approaches, defensive or offensive behaviors, and choices related to their self-efficacy. The aim of this study was to identify approaches used in the RTW process among women with neck pain on long-term sick leave from human service organizations. Methods This is a qualitative descriptive study based on grounded theory. A Swedish cohort of 207 women with a history of long-term sick leave with neck pain from human service organizations answered open-ended written questions at 0, 6, and 12 months, and 6 years; and 16 women were interviewed. Results Individuals expressed their coping approaches in terms of fluctuating in work status over time: either as a strategy or as a consequence. Periods of sick leave were interwoven with periods of work. The women were either controlling the interaction or struggling in the interaction with stakeholders. Conclusions Return to work outcomes may be improved if the fluctuating work status over time is taken into account in the design of rehabilitation efforts for women with a history of long-term sick leave and with chronical musculoskeletal conditions.

  • 47.
    Ahlstrom, L
    et al.
    Sahlgrenska Akademin.
    Hagberg, M
    Sahlgrenska Akademin.
    Dellve, Lotta
    KTH, School of Technology and Health (STH), Ergonomics.
    Workplace Rehabilitation and Supportive Conditions at Work: A Prospective Study2013In: Journal of occupational rehabilitation, ISSN 1053-0487, E-ISSN 1573-3688, Vol. 23, no 2, p. 248-260Article in journal (Refereed)
    Abstract [en]

    Purpose To investigate the impact of rehabilitation measures on work ability and return to work (RTW), specifically the association between workplace rehabilitation/supportive conditions at work and work ability and RTW over time, among women on long-term sick leave. Methods Questionnaire data were collected (baseline, 6 and 12 months) from a cohort of women (n = 324). Linear mixed models were used for longitudinal analysis of the repeated measurements of work ability index (WAI), work ability score and working degree. These analyses were performed with different models; the explanatory variables for each model were workplace rehabilitation, supportive conditions at work and time. Results The individuals provided with workplace rehabilitation and supportive conditions (e.g. influence at work, possibilities for development, degree of freedom at work, meaning of work, quality of leadership, social support, sense of community and work satisfaction) had significantly increased WAI and work ability score over time. These individuals scored higher work ability compared to those individuals having workplace rehabilitation without supportive conditions, or neither. Additionally, among the individuals provided with workplace rehabilitation and supportive conditions, working degree increased significantly more over time compared to those individuals with no workplace rehabilitation and no supportive conditions. Conclusion The results highlight the importance of integrating workplace rehabilitation with supportive conditions at work in order to increase work ability and improve the RTW process for women on long-term sick leave.

  • 48.
    Ahlstrom, Linda
    et al.
    Sahlgrenska akademin, Göteborgs universitet.
    Grimby-Ekman, Anna
    Sahlgrenska akademin, Göteborgs universitet.
    Hagberg, Mats
    Sahlgrenska akademin, Göteborgs universitet.
    Dellve, Lotta
    Sahlgrenska akademin, Göteborgs universitet.
    Measures of work ability and association with sick leave, symptoms and health: A prospective study of female workers on long term sick leave2010In: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, E-ISSN 1795-990X, Vol. 36, no 5, p. 404-412Article in journal (Refereed)
  • 49.
    Ahlstrom, Linda
    et al.
    Högskolan Borås.
    Larsson Fallman, Sara
    Högskolan Borås.
    Dellve, Lotta
    KTH, School of Technology and Health (STH), Health Systems Engineering, Ergonomics. Public Health and Community Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Return to work from long-term sick leave: a five-year prospective study of the importance of adjustment latitudes at work and home2014Conference paper (Other academic)
    Abstract [en]

    Background

    Adjustment latitude among employees, i.e. adjusting work to individual’s health capacity, has been associated with successful return to work (RTW) in cross-sectional studies. The aim is to investigate the long-term importance of adjustment latitude at the workplace and at home, as well as attitudes (own and colleagues) for increased work ability (WA), working degree (WD) and health-related quality of life (HRQoL) among female human service workers (HSW) on long-term sick leave in Sweden.

    Methods

    A cohort of female HSW (n=324) on long-term sick leave (>60 day) received a questionnaire at four times (0, 6, 12, 60 months). Prevalence ratios (PR) were used to examine possible relationships between explanatory factors and outcomes. Linear mixed models were used for longitudinal analysis of the repeated measurements of WA Score (0-10), WD (0-100%) and HRQoL (0-100). Analyses were performed with different models; the explanatory variables for each model were adjustment latitude, attitudes towards breaks at work, shared or single household and amount of household work.

    Result

    Having more adjustment latitude at work was associated with both increased WA and RTW compared to having few adjustment latitude opportunities. Adjustments related to working-pace were strongly associated with increased WD (PR 3.29(95%CI=1.71-6.26)), as were adjustments to working-place. Having opportunities to take short breaks at work, and a general acceptance at work to take short breaks was associated with increased WA. At home, a higher responsibility for household work (PR 1.98(95%CI=1.33-2.95)) was related to increased WA and RTW. Individuals with possibilities for adjustment latitude, especially pace and place, at work, and an acceptance to take breaks at work, increased in WA score significantly more over time and had higher WA score compared with individuals not having such opportunities at work. These prospective results were similar for the outcome WD and HRQoL.

    Conclusions

    The results highlight the importance of possibilities for adjustment latitude at work and at home, as well as accepting attitudes to take short breaks to increase WA and RTW among female human service workers previously on long-term sick leave.

  • 50.
    Ahltorp, Magnus
    et al.
    KTH.
    Skeppstedt, M.
    Dalianis, H.
    Kvist, M.
    Using text prediction for facilitating input and improving readability of clinical text2013In: Studies in Health Technology and Informatics, IOS Press, 2013, no 1-2, p. 1149-Conference paper (Refereed)
    Abstract [en]

    Text prediction has the potential for facilitating and speeding up the documentation work within health care, making it possible for health personnel to allocate less time to documentation and more time to patient care. It also offers a way to produce clinical text with fewer misspellings and abbreviations, increasing readability. We have explored how text prediction can be used for input of clinical text, and how the specific challenges of text prediction in this domain can be addressed. A text prediction prototype was constructed using data from a medical journal and from medical terminologies. This prototype achieved keystroke savings of 26% when evaluated on texts mimicking authentic clinical text. The results are encouraging, indicating that there are feasible methods for text prediction in the clinical domain.

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