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  • 1.
    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.

  • 2.
    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.

  • 3.
    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.

  • 4.
    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.

  • 5.
    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.

  • 6. 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.

  • 7.
    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.

  • 8.
    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.

  • 9. 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.

  • 10.
    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.

  • 11.
    Ahmad, T.
    et al.
    Department of Cardiology.
    Ali, U.
    Department of Cardiology.
    Shah, S. T.
    Department of Cardiology.
    Khan, A.
    Department of Cardiology.
    Ul Hadi, N.
    Frequency and outcomes of undiagnosed diabetes mellitus in patients presenting with acute myocardial infarction2020In: Medical Forum Monthly, ISSN 1029-385X, Vol. 31, no 12, p. 3-7Article in journal (Refereed)
    Abstract [en]

    Objective: To find out frequency and outcomes of undiagnosed diabetes mellitus in patients presenting with acute ST elevation myocardial infarction (STEMI). Study Design: Descriptive / Cross-Sectional Study Place and Duration of study: This study was conducted at the Cardiology Department, Lady Reading Hospital, Peshawar from November 2018 to May 2019. Materials and Methods: Patient of either gender having age ranging between 30-75 years old with acute STEMI who present within 12 hours of symptoms and with no past history of documented diabetes mellitus were included in the study. Venous blood samples for laboratory data, including random blood sugar, two fasting blood sugar and HBA1c using hitachi modular evo p800 machine was done. Results: A total of 158 patients having acute STEMI were studied. Males were 68.4% (n=108).The mean age was 59.65 ±10.80 years. Frequency of undiagnosed diabetes mellitus was 31.64 % (n = 50). In non-diabetics stress hyperglycemia was found in 51.85 % (n=56) patients. Among various types of STEMI, anterior STEMI was more common presentation 34.1 % (n=54. p= 0.85). Mean HBA1C was 6.19 ± 1.87%. Frequency of Ventricular tachycardia (VT) was 22.2 % in which undiagnosed diabetics were n=18 (p=0.004).Ventricular fibrillation was present in 13.3 % patients with undiagnosed diabetics were n=14 (p=0.001). Frequency of AF was 13.9% (n=22) with undiagnosed diabetics having AF in n=13 (p=0.003). SVT was present in 5.7% (n=9) patients with not significant difference between two groups (p=0.017). Among various mechanical complications VSR was present in 10 % (n=16) of patients (p=0.001), cardiogenic shock in 11.1 % (n=18) patients (p=0.004), acute LVF was present in 15.8 % patients (p=0.017). Conclusion: In our study we concluded that one third of patients having acute ST elevation myocardial infarction have undiagnosed diabetes mellitus (31.64 %, n = 50). The most common complication was ventricular tachycardia among electrical complication and LVF among mechanical complication.

  • 12. Aitken, Candice L.
    et al.
    Gorniak, Richard J. T.
    New York University.
    Kramer, Elissa L.
    New York University.
    Noz, Marilyn E.
    New York University.
    Farrell, Eward J.
    IBM Research.
    Maguire Jr., Gerald Q.
    KTH, Superseded Departments (pre-2005), Teleinformatics.
    Reddy, David P.
    Comparison of three methods used for fusion of SPECT-CT images of liver matastases1998In: Fusion98, International Conference on Multisource-Mulltisensor Information Fusion / [ed] Hamid R. Arabnia and Dongping (Daniel) Zhu, CSREA Press , 1998, p. 435-442Conference paper (Refereed)
    Abstract [en]

    We compare three methods for fusing SPECT-CT images: ImageMatch - an automatic three-dimensional/two-dimensional method developed by Focus Imaging; IBM Visualization Data Explorer - a three-diemensional interactive method developed by Internation Business Machines, Inc.; and qsh - an interactive three-dimensional/two-dimensional method developed at New York University. While many fusion methods have proved successful for registering brain images, most methods have been less successful for thoracic and abdominal images. We use images of liver metastases obtained with a radiolabeled breast tumor-directed antibody to illustrate the strengths and weakness of the methods reviewed. The images used are typical clinical images from eigth patients. We conclude that an optimal image fusion program should combine the strengths of each of the methods reviewed.

  • 13. Aitken, Candice L.
    et al.
    Mahmoud, Faaiza
    McGuinness, Georgeann
    Kramer, Elissa L.
    Maguire, Gerald Q. Jr.
    KTH, Superseded Departments (pre-2005), Microelectronics and Information Technology, IMIT.
    Noz, Marilyn E.
    New York University.
    Tumor localization and image registration of F-18FDG coincidence detection scans with computed tomographic scans2002In: Clinical Nuclear Medicine, ISSN 0363-9762, E-ISSN 1536-0229, Vol. 27, no 4, p. 275-282Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of this study was to determine the feasibility of registering routine clinical F-18 fluorodeoxyglucose (FDG) coincidence detection (CD) scans with computed tomographic (CT) scans for radiation treatment planning and case management. Methods: F-18 FDG CD and chest CT scans, performed in 10 randomly selected patients with confirmed or possible adenocarcinoma of the lung, were evaluated. The quality of the matches was verified by comparisons of the center-to-center distance between a region of interest (ROI) manually drawn on the CT slice and warped onto the CD slice with an ROI drawn manually directly on the CD slice. In addition, the overlap between the two ROIs was calculated. Results: All 10 F-18 FDG CD and CT scans were registered with good superimposition of soft tissue density on increased radionuclide activity. The center-to-center distance between the ROIs ranged from 0.29 mm to 8.08 mm, with an average center-to-center distance of 3.89 mm 2.42 mm (0.69 pixels +/- 0.34 pixels). The ROI overlap ranged from 77% to 99%, with an average of 90% +/- 5.6%. Conclusions: Although the use of F-18 FDG CD shows great promise for the identification of tumors, it shares the same drawbacks as those associated with radiolabeled monoclonal antibody SPECT and ligand-based positron emission tomographic scans in that anatomic markers are limited. This study shows that image registration is feasible and may improve the clinical relevance of CD images.

  • 14.
    Aitken, Candice L.
    et al.
    New York University.
    McGuinness, Georgeann
    New York University.
    Siddiqui, Faaiza
    New York University.
    Ton, Anthony
    New York University.
    Kramer, Elissa L
    New York University.
    Maguire Jr., Gerald Q.
    KTH, Superseded Departments (pre-2005), Teleinformatics.
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Tumor localization and image registration of 18-FDG SPECT scans with CT scans1999In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 40, no 5, p. 290P-291PArticle in journal (Refereed)
    Abstract [en]

    PURPOSE:

    The aim of this study was to determine the feasibility of registering routine clinical F-18 fluorodeoxyglucose (FDG) coincidence detection (CD) scans with computed tomographic (CT) scans for radiation treatment planning and case management.

    METHODS:

    F-18 FDG CD and chest CT scans, performed in 10 randomly selected patients with confirmed or possible adenocarcinoma of the lung, were evaluated. The quality of the matches was verified by comparisons of the center-to-center distance between a region of interest (ROI) manually drawn on the CT slice and warped onto the CD slice with an ROI drawn manually directly on the CD slice. In addition, the overlap between the two ROIs was calculated.

    RESULTS:

    All 10 F-18 FDG CD and CT scans were registered with good superimposition of soft tissue density on increased radionuclide activity. The center-to-center distance between the ROIs ranged from 0.29 mm to 8.08 mm, with an average center-to-center distance of 3.89 mm +/- 2.42 mm (0.69 pixels +/- 0.34 pixels). The ROI overlap ranged from 77% to 99%, with an average of 90% +/- 5.6%.

    CONCLUSIONS:

    Although the use of F-18 FDG CD shows great promise for the identification of tumors, it shares the same drawbacks as those associated with radiolabeled monoclonal antibody SPECT and ligand-based positron emission tomographic scans in that anatomic markers are limited. This study shows that image registration is feasible and may improve the clinical relevance of CD images.

  • 15.
    Akan, Rabia
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Lundberg, Fabian
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Ohlin, Hanna
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Johansson, Ulf
    Lund Univ, MAX IV Lab, S-22100 Lund, Sweden..
    Li, Kenan
    SLAC Natl Accelerator Lab, 2575 Sand Hill Rd, Menlo Pk, CA 94025 USA..
    Sakdinawat, Anne
    SLAC Natl Accelerator Lab, 2575 Sand Hill Rd, Menlo Pk, CA 94025 USA..
    Vogt, Ulrich
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Metal-Assisted Chemical Etching and Electroless Deposition for Fabrication of Hard X-ray Pd/Si Zone Plates2020In: Micromachines, E-ISSN 2072-666X, Vol. 11, no 3, article id 301Article in journal (Refereed)
    Abstract [en]

    Zone plates are diffractive optics commonly used in X-ray microscopes. Here, we present a wet-chemical approach for fabricating high aspect ratio Pd/Si zone plate optics aimed at the hard X-ray regime. A Si zone plate mold is fabricated via metal-assisted chemical etching (MACE) and further metalized with Pd via electroless deposition (ELD). MACE results in vertical Si zones with high aspect ratios. The observed MACE rate with our zone plate design is 700 nm/min. The ELD metallization yields a Pd density of 10.7 g/cm3, a value slightly lower than the theoretical density of 12 g/cm3. Fabricated zone plates have a grid design, 1:1 line-to-space-ratio, 30 nm outermost zone width, and an aspect ratio of 30:1. At 9 keV X-ray energy, the zone plate device shows a first order diffraction efficiency of 1.9%, measured at the MAX IV NanoMAX beamline. With this work, the possibility is opened to fabricate X-ray zone plates with low-cost etching and metallization methods.

  • 16.
    Akerlund, Cecilia A., I
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Sect Anaesthesiol & Intens Care, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Funct Perioperat Med & Intens Care, Stockholm, Sweden..
    Holst, Anders
    KTH, School of Electrical Engineering and Computer Science (EECS), Computer Science, Computational Science and Technology (CST).
    Bhattacharyay, Shubhayu
    Univ Cambridge, Dept Med, Div Anaesthesia, Cambridge, England..
    Stocchetti, Nino
    Univ Cambridge, Cambridge, England.;Milan Univ, Dept Physiopathol & Transplant, Milan, Italy.;Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Milan, Italy..
    Steyerberg, Ewout
    Leiden Univ Med Ctr, Dept Biomed Data Sci, Leiden, Netherlands..
    Smielewski, Peter
    Univ Cambridge, Clin Neurosci, Cambridge, England..
    Menon, David K.
    Univ Cambridge, Dept Med, Div Anaesthesia, Cambridge, England..
    Ercole, Ari
    Univ Cambridge, Dept Med, Div Anaesthesia, Cambridge, England.;Univ Cambridge, Ctr Artificial Intelligence Med, Cambridge, England..
    Nelson, David W.
    Karolinska Inst, Dept Physiol & Pharmacol, Sect Anaesthesiol & Intens Care, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Funct Perioperat Med & Intens Care, Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Sect Anaesthes & Intens Care, S-171 77 Stockholm, Sweden..
    Clinical descriptors of disease trajectories in patients with traumatic brain injury in the intensive care unit (CENTER-TBI): a multicentre observational cohort study2024In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 23, no 1, p. 71-80Article in journal (Refereed)
    Abstract [en]

    Background Patients with traumatic brain injury are a heterogeneous population, and the most severely injured individuals are often treated in an intensive care unit (ICU). The primary injury at impact, and the harmful secondary events that can occur during the first week of the ICU stay, will affect outcome in this vulnerable group of patients. We aimed to identify clinical variables that might distinguish disease trajectories among patients with traumatic brain injury admitted to the ICU. Methods We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. We included patients aged 18 years or older with traumatic brain injury who were admitted to the ICU at one of the 65 CENTER-TBI participating centres, which range from large academic hospitals to small rural hospitals. For every patient, we obtained pre-injury data and injury features, clinical characteristics on admission, demographics, physiological parameters, laboratory features, brain biomarkers (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1], S100 calcium-binding protein B [S100B], tau, neurofilament light [NFL], glial fibrillary acidic protein [GFAP], and neuron-specific enolase [NSE]), and information about intracranial pressure lowering treatments during the first 7 days of ICU stay. To identify clinical variables that might distinguish disease trajectories, we applied a novel clustering method to these data, which was based on a mixture of probabilistic graph models with a Markov chain extension. The relation of clusters to the extended Glasgow Outcome Scale (GOS-E) was investigated. Findings Between Dec 19, 2014, and Dec 17, 2017, 4509 patients with traumatic brain injury were recruited into the CENTER-TBI core dataset, of whom 1728 were eligible for this analysis. Glucose variation (defined as the difference between daily maximum and minimum glucose concentrations) and brain biomarkers (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were consistently found to be the main clinical descriptors of disease trajectories (ie, the leading variables contributing to the distinguishing clusters) in patients with traumatic brain injury in the ICU. The disease trajectory cluster to which a patient was assigned in a model was analysed as a predictor together with variables from the IMPACT model, and prediction of both mortality and unfavourable outcome (dichotomised GOS-E <= 4) was improved. Interpretation First-day ICU admission data are not the only clinical descriptors of disease trajectories in patients with traumatic brain injury. By analysing temporal variables in our study, variation of glucose was identified as the most important clinical descriptor that might distinguish disease trajectories in the ICU, which should direct further research. Biomarkers of brain injury (S100B, NSE, NFL, tau, UCH-L1, and GFAP) were also top clinical descriptors over time, suggesting they might be important in future clinical practice.

  • 17.
    Akkus, Zeynettin
    et al.
    KTH. Department of Medical Physics, University Hospitals of Leicester, NHS Trust, Leicester, UK.
    Ramnarine, K. V.
    Dynamic assessment of carotid plaque motion2010In: Ultrasound, ISSN 1742-271X, Vol. 18, no 3, p. 140-147Article in journal (Refereed)
    Abstract [en]

    Assessment of dynamic plaque behaviour may help identify vulnerable carotid plaque before rupture and hence has potential clinical value for screening patients at risk of stroke. The aim of this study was to develop non-invasive ultrasound methods for quantifying dynamic plaque and vessel wall behaviour and assess their potential clinical utility. Ultrasound data from the carotid arteries of one normal subject and four patients with atherosclerotic disease were acquired using a 10 MHz linear array transducer recording raw RF/IQ data at a frame rate up to 80 Hz for 3-6 seconds. Image reconstruction and processing was performed using Matlab. Speckle tracking techniques were developed to characterize: (1) intraplaque deformation; and (2) plaque surface and vessel wall motion. Speckle tracking techniques were able to measure the range of intraplaque tissue deformation (-1.3 to 1.7 mm), plaque surface displacement (0.2-0.7 mm) and vessel wall radial strain (0.02-0.13) throughout the cardiac cycle. The feasibility of using an intraplaque deformation parameter, based on the deformation of a square template, is demonstrated. Speckle tracking techniques can be used to assess dynamic carotid plaque behaviour. Further work is required to evaluate how best to quantify biomechanical behaviour to help predict plaque rupture and hence improve risk stratification models for stroke.

  • 18.
    Alagic, Zlatan
    et al.
    Karolinska Univ Hosp, Funct Unit Musculoskeletal Radiol Funct Imaging &, S-17176 Stockholm, Sweden.;Karolinska Inst, Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden..
    Alagic, Haris
    Karolinska Inst, Inst Mol Med & Surg MMK, Diagnost Radiol, Stockholm, Sweden..
    Bujila, Robert
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Srivastava, Subhash
    Karolinska Univ Hosp, Funct Unit Musculoskeletal Radiol Funct Imaging &, S-17176 Stockholm, Sweden..
    Jasim, Saif
    Karolinska Univ Hosp, Funct Unit Musculoskeletal Radiol Funct Imaging &, S-17176 Stockholm, Sweden..
    Lindqvist, Maria
    Karolinska Univ Hosp, Funct Unit Musculoskeletal Radiol Funct Imaging &, S-17176 Stockholm, Sweden..
    Wick, Marius C.
    Karolinska Univ Hosp, Funct Unit Musculoskeletal Radiol Funct Imaging &, S-17176 Stockholm, Sweden.;Karolinska Inst, Inst Mol Med & Surg MMK, Diagnost Radiol, Stockholm, Sweden..
    First experiences of a low-dose protocol for CT-guided musculoskeletal biopsies combining different radiation dose reduction techniques2020In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 61, no 1, p. 28-36Article in journal (Refereed)
    Abstract [en]

    Background The use of computed tomography (CT) for image guidance during biopsies is a powerful approach. The method is, however, often associated with a significant level of radiation exposure to the patient and operator. Purpose To investigate if a low-dose protocol for CT-guided musculoskeletal (MSK) biopsies, including a combination of different radiation dose (RD) techniques, is feasible in a clinical setting. Material and Methods Fifty-seven patients underwent CT-guided fine-needle aspiration cytology (FNAC) utilizing the low-dose protocol (group A). A similar number of patients underwent CT-guided FNAC using the reference protocol (group B). Between-group comparisons comprised radiation dose, success rate, image quality parameters, and workflow. Results In group A, the mean total dose-length product (DLP) was 41.2 +/- 2.9 mGy*cm, which was statistically significantly lower than of group B (257.4 +/- 22.0 mGy*cm), corresponding to a mean dose reduction of 84% (P<0.001). The mean CTDIvol for the control scans were 1.88 +/- 0.09 mGy and 13.16 +/- 0.40 mGy for groups A and B, respectively (P < 0.001). The success rate in group A was 91.2% and 87.9% in group B (P = 0.56). No negative effect on image-quality parameters, time of FNAC, and number of control scans were found. Conclusion We successfully developed a low-dose protocol for CT-guided MSK biopsies that maintains diagnostic accuracy and image quality at a fraction of the RD compared to the reference biopsy protocol at our clinic.

  • 19.
    Alarcon, Aixa
    et al.
    Johnson Johnson Surg Vision Inc, Groningen, Netherlands..
    Canovas, Carmen
    Johnson Johnson Surg Vision Inc, Groningen, Netherlands..
    Van der Mooren, Marrie
    Johnson Johnson Surg Vision Inc, Groningen, Netherlands..
    Janakiraman, Priya
    Johnson Johnson Surg Vision Inc, Groningen, Netherlands..
    Rosen, Robert
    Johnson Johnson Surg Vision Inc, Groningen, Netherlands..
    Lundström, Linda
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Chang, Daniel H.
    Empire Eye Laser Ctr, Bakersfield, CA USA..
    Clinical measurements of peripheral contrast sensitivity in elderly phakic and pseudophakic eyes2022In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 63, no 7Article in journal (Other academic)
  • 20.
    Alcala, Yvonne
    et al.
    New York Medical College .
    Olivecrona, Henrik
    Karolinska.
    Olivecrona, Lotta
    Karolinska.
    Noz, Marilyn E.
    New York University.
    Maguire Jr., Gerald Q.
    KTH, School of Information and Communication Technology (ICT), Microelectronics and Information Technology, IMIT.
    Zeleznik, Michael P.
    Sollerman, Christer
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Qualifying CT for wrist arthroplasty: Extending techniques for total hip arthroplasty to total wrist arthroplasty2005In: Medical Imaging 2005: Image Processing, Pt 1-3 / [ed] Fitzpatrick, JM; Reinhardt, JM, SPIE - The International Sooceity for Optical Engineeering , 2005, Vol. 5747, p. 1155-1164Conference paper (Refereed)
    Abstract [en]

    The purpose of this study was to extend previous work to detect migration of total wrist arthroplasty non-invasively, and with greater accuracy. Two human cadaverous arms, each with a cemented total wrist implant, were used in this study. In one of the arms, I mm tantalum balls were implanted, six in the carpal bones and five in the radius. Five CT scans of each arm were acquired, changing the position of the arm each time to mimic different positions patients might take on repeated examinations. Registration of CT volume data sets was performed using an extensively validated, 3D semi-automatic volume fusion tool in which co-homologous point pairs (landmarks) are chosen on each volume to be registered. Three sets of ten cases each were obtained by placing landmarks on 1) bone only (using only arm one), 2) tantalum implants only, and 3) bone and tantalum implants (both using only arm two). The accuracy of the match was assessed visually in 2D and 3D, and numerically by calculating the distance difference between the actual position of the transformed landmarks and their ideal position (i.e., the reference landmark positions). All cases were matched visually within one width of cortical bone and numerically within one half CT voxel (0.32 mm, p = 0.05). This method matched only the bone/arm and not the prosthetic component per se, thus making it possible to detect prosthetic movement and wear. This method was clinically used for one patient with pain. Loosening of the carpal prosthetic component was accurately detected and this was confirmed at surgery.

  • 21.
    Al-Farsi, Hissa M.
    et al.
    Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.;Minist Hlth, Cent Publ Hlth Labs, Muscat, Oman..
    Al-Adwani, Salma
    Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.;Sultan Qaboos Univ, Coll Agr & Marine Sci, Dept Anim & Vet Sci, Muscat, Oman..
    Ahmed, Sultan
    Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden..
    Vogt, Carmen
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Ambikan, Anoop T.
    Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden..
    Leber, Anna
    Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden..
    Al-Jardani, Amina
    Minist Hlth, Cent Publ Hlth Labs, Muscat, Oman..
    Al-Azri, Saleh
    Minist Hlth, Cent Publ Hlth Labs, Muscat, Oman..
    Al-Muharmi, Zakariya
    Sultan Qaboos Univ, Coll Med & Hlth Sci, Dept Microbiol & Immunol, Muscat, Oman..
    Toprak, Muhammet
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Giske, Christian G.
    Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Microbiol, Stockholm, Sweden..
    Bergman, Peter
    Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.;Karolinska Univ Hosp, Immunodeficiency Unit, Infect Dis Clin, Stockholm, Sweden..
    Effects of the Antimicrobial Peptide LL-37 and Innate Effector Mechanisms in Colistin-Resistant Klebsiella pneumoniae With mgrB Insertions2019In: Frontiers in Microbiology, E-ISSN 1664-302X, Vol. 10, article id 2632Article in journal (Refereed)
    Abstract [en]

    Background Colistin is a polypeptide antibiotic drug that targets lipopolysaccharides in the outer membrane of Gram-negative bacteria. Inactivation of the mgrB-gene is a common mechanism behind colistin-resistance in Klebsiella pneumoniae (Kpn). Since colistin is a cyclic polypeptide, it may exhibit cross-resistance with the antimicrobial peptide LL-37, and with other innate effector mechanisms, but previous results are inconclusive. Objective To study potential cross-resistance between colistin and LL-37, as well as with other innate effector mechanisms, and to compare virulence of colistin-resistant and susceptible Kpn strains. Materials/Methods Carbapenemase-producing Kpn from Oman (n = 17) were subjected to antimicrobial susceptibility testing and whole genome sequencing. Susceptibility to colistin and LL-37 was studied. The surface charge was determined by zeta-potential measurements and the morphology of treated bacteria was analyzed with electron microscopy. Bacterial survival was assessed in human whole blood and serum, as well as in a zebrafish infection-model. Results Genome-analysis revealed insertion-sequences in the mgrB gene, as a cause of colistin resistance in 8/17 isolates. Colistin-resistant (Col-R) isolates were found to be more resistant to LL-37 compared to colistin-susceptible (Col-S) isolates, but only at concentrations >= 50 mu g/ml. There was no significant difference in surface charge between the isolates. The morphological changes were similar in both Col-R and Col-S isolates after exposure to LL-37. Finally, no survival difference between the Col-R and Col-S isolates was observed in whole blood or serum, or in zebrafish embryos. Conclusion Cross-resistance between colistin and LL-37 was observed at elevated concentrations of LL-37. However, Col-R and Col-S isolates exhibited similar survival in serum and whole blood, and in a zebrafish infection-model, suggesting that cross-resistance most likely play a limited role during physiological conditions. However, it cannot be ruled out that the observed cross-resistance could be relevant in conditions where LL-37 levels reach high concentrations, such as during infection or inflammation.

  • 22.
    Alfredsson, P. Henrik
    et al.
    KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW. KTH, School of Engineering Sciences (SCI), Engineering Mechanics.
    Kato, Kentaro
    Shinshu Univ, Dept Mech Syst Engn, Nagano, Japan..
    Lingwood, Rebecca
    KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW. KTH, School of Engineering Sciences (SCI), Engineering Mechanics.
    Flows Over Rotating Disks and Cones2024In: Annual Review of Fluid Mechanics, ISSN 0066-4189, E-ISSN 1545-4479, Vol. 56, p. 45-68Article, review/survey (Refereed)
    Abstract [en]

    Rotating-disk flows were first considered by von Karman in a seminal paper in 1921, where boundary layers in general were discussed and, in two of the nine sections, results for the laminar and turbulent boundary layers over a rotating disk were presented. It was not until in 1955 that flow visualization discovered the existence of stationary cross-flow vortices on the disk prior to the transition to turbulence. The rotating disk can be seen as a special case of rotating cones, and recent research has shown that broad cones behave similarly to disks, whereas sharp cones are susceptible to a different type of instability. Here, we provide a review of the major developments since von Karman's work from 100 years ago, regarding instability, transition, and turbulence in the boundary layers, and we include some analysis not previously published.

  • 23.
    Ali, Muhedin
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Gebele, Elin
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Temperaturens och omrörningstidens inverkan på storleksfördelning, diameter och koncentration av mikrodroppar2023Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The aim of this study was to fabricate and measure the concentration, diameter, size distribution of microdroplets under different temperatures and stirring times. The data collection came from several observations which provided a thorough understanding of its properties under different circumstances.

    One of the key findings was that the temperature had an important role in the concentration of microdroplets. A decrease in concentration levels was observed at lower temperatures. Furthermore, it was noted that stirring time also played a role, leading to significant reductions in the total number of microdroplets when observed for longer stirring times.

    The mean diameters of the microdroplets had sizes that were within acceptable ranges in all samples. The mean diameters observed ranged from sizes between 3.98 μm and 8.18 μm but single microdroplets with diameters greater than 10 μm could also be found and observed.

    The results provided guiding factors for further investigations to determine its medical applications. Future studies should continue to analyze these parameters to further optimize microdroplets for use in areas such as ultrasound imaging or drug delivery.

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  • 24.
    Aljadi, Zenib
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden.
    Kalm, Frida
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden;Sachs´ Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
    Nilsson, Caroline
    Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden.;Soder Sjukhuset, Sachs Children & Youth Hosp, Stockholm, Sweden..
    Winqvist, Ola
    Karolinska Univ Hosp, Dept Clin Immunol, Stockholm, Sweden..
    Russom, Aman
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Lundahl, Joachim
    Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden.;Soder Sjukhuset, Sachs Children & Youth Hosp, Stockholm, Sweden..
    Nopp, Anna
    Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden.;Soder Sjukhuset, Sachs Children & Youth Hosp, Stockholm, Sweden..
    A novel tool for clinical diagnosis of allergy operating a microfluidic immunoaffinity basophil activation test technique2019In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 209, article id UNSP 108268Article in journal (Refereed)
    Abstract [en]

    The Basophil Activation Test (BAT) is a valuable allergy diagnostic tool but is time-consuming and requires skilled personnel and cumbersome processing, which has limited its clinical use. We therefore investigated if a microfluidic immunoaffinity BAT (miBAT) technique can be a reliable diagnostic method. Blood was collected from allergic patients and healthy controls. Basophils were challenged with negative control, positive control (anti-FccRI), and two concentrations of a relevant and non-relevant allergen. CD203c and CD63 expression was detected by fluorescent microscopy and flow cytometry. In basophils from allergic patients the CD63% was significantly higher after allergen activation as compared to the negative control (p < .0001-p = .0004). Activation with non-relevant allergen showed equivalent CD63% expression as the negative control. Further, the miBAT data were comparable to flow cytometry. Our results demonstrate the capacity of the miBAT technology to measure different degrees of basophil allergen activation by quantifying the CD63% expression on captured basophils.

  • 25.
    Aljadi, Zenib
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden; Soder Sjukhuset, Stockholm, Sweden .
    Kalm, Frida
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden; Soder Sjukhuset, Stockholm, Sweden.
    Ramachandraiah, Harisha
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nopp, Anna
    Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden.;Soder Sjukhuset, Stockholm, Sweden..
    Lundahl, Joachim
    Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden.;Soder Sjukhuset, Stockholm, Sweden..
    Russom, Aman
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Microfluidic Immunoaffinity Basophil Activation Test for Point-of-Care Allergy Diagnosis2019In: Journal of Applied Laboratory Medicine (JALM), ISSN 2475-7241, Vol. 4, no 2, p. 152-163Article in journal (Refereed)
    Abstract [en]

    Background: The flow cytometry-based basophil activation test (BAT) is used for the diagnosis of allergic response. However, flow cytometry is time-consuming, requiring skilled personnel and cumbersome processing, which has limited its use in the clinic. Here, we introduce a novel microfluidic-based immunoaffinity BAT (miBAT) method. Methods: The microfluidic device, coated with anti-CD203c, was designed to capture basophils directly from whole blood. The captured basophils are activated by anti-FceRI antibody followed by optical detection of CD63 expression (degranulation marker). The device was first characterized using a basophil cell line followed by whole blood experiments. Weevaluated the device with ex vivo stimulation of basophils in whole blood from healthy controls and patients with allergies and compared it with flow cytometry. Results: The microfluidic device was capable of capturing basophils directly from whole blood followed by in vitro activation and quantification of CD63 expression. CD63 expression was significantly higher (P = 0.0002) in on-chip activated basophils compared with nonactivated cells. The difference in CD63 expression on anti-FceRI-activated captured basophils in microfluidic chip was significantly higher (P = 0.03) in patients with allergies compared with healthy controls, and the results were comparable with flow cytometry analysis (P = 0.04). Furthermore, there was no significant difference of CD63% expression in anti-FceRI-activated captured basophils in microfluidic chip compared with flow cytometry. Conclusions: We report on the miBAT. This device is capable of isolating basophils directly from whole blood for on-chip activation and detection. The new miBAT method awaits validation in larger patient populations to assess performance in diagnosis and monitoring of patients with allergies at the point of care.

  • 26.
    Alkharaan, Hassan
    et al.
    Karolinska Inst, Dept Dent Med, Alfred Nobels Alle 8, S-14104 Stockholm, Sweden..
    Bayati, Shaghayegh
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hellström, Cecilia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Aleman, Soo
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Olsson, Annika
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden..
    Lindahl, Karin
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Bogdanovic, Gordana
    Karolinska Univ Hosp, Dept Clin Microbiol, Stockholm, Sweden..
    Healy, Katie
    Karolinska Inst, Dept Dent Med, Alfred Nobels Alle 8, S-14104 Stockholm, Sweden..
    Tsilingaridis, Georgios
    Karolinska Inst, Dept Dent Med, Alfred Nobels Alle 8, S-14104 Stockholm, Sweden..
    De Palma, Patricia
    Karolinska Inst, Dept Dent Med, Alfred Nobels Alle 8, S-14104 Stockholm, Sweden..
    Hober, Sophia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Technology.
    Månberg, Anna
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Pin, Elisa
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Chen, Margaret Sallberg
    Karolinska Inst, Dept Dent Med, Alfred Nobels Alle 8, S-14104 Stockholm, Sweden..
    Persisting Salivary IgG Against SARS-CoV-2 at 9 Months After Mild COVID-19: A Complementary Approach to Population Surveys2021In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 224, no 3, p. 407-414Article in journal (Refereed)
    Abstract [en]

    Background. Declining humoral immunity in coronavirus disease 2019 (COVID-19) patients and possible reinfection have raised concern. Mucosal immunity, particularly salivary antibodies, may be short lived although long-term studies are lacking. Methods. Using a multiplex bead-based array platform, we investigated antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins in 256 saliva samples from convalescent patients 1-9 months after symptomatic COVID-19 (n = 74, cohort 1), undiagnosed individuals with self-reported questionnaires (n = 147, cohort 2), and individuals sampled prepandemic (n = 35, cohort 3). Results. Salivary IgG antibody responses in cohort 1 (mainly mild COVID-19) were detectable up to 9 months postrecovery, with high correlations between spike and nucleocapsid specificity. At 9 months, IgG remained in blood and saliva in most patients. Salivary IgA was rarely detected at this time point. In cohort 2, salivary IgG and IgA responses were significantly associated with recent history of COVID-19-like symptoms. Salivary IgG tolerated temperature and detergent pretreatments. Conclusions. Unlike SARS-CoV-2 salivary IgA that appeared short lived, specific saliva IgG appeared stable even after mild COVID-19, as for blood serology. This noninvasive saliva-based SARS-CoV-2 antibody test with home self-collection may be a complementary alternative to conventional blood serology.

  • 27. Alkharusi, Amira
    et al.
    Yu, Shengze
    KTH, School of Biotechnology (BIO).
    Landazuri, Natalia
    Zadjali, Fahad
    Davodi, Belghis
    Nystrom, Thomas
    Gräslund, Torbjörn
    KTH, School of Biotechnology (BIO), Protein Technology.
    Rahbar, Afsar
    Norstedt, Gunnar
    Stimulation of prolactin receptor induces STAT-5 phosphorylation and cellular invasion in glioblastoma multiforme2016In: Oncotarget, E-ISSN 1949-2553, Vol. 7, no 48, p. 79558-79569Article in journal (Refereed)
    Abstract [en]

    Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in humans and is characterized with poor outcome. In this study, we investigated components of prolactin (Prl) system in cell models of GBM and in histological tissue sections obtained from GBM patients. Expression of Prolactin receptor (PrlR) was detected at high levels in U251-MG, at low levels in U87-MG and barely detectable in U373 cell lines and in 66% of brain tumor tissues from 32 GBM patients by immunohistochemical technique. In addition, stimulation of U251-MG and U87-MG cells but not U373 with Prl resulted in increased STAT5 phosphorylation and only in U251-MG cells with increased cellular invasion. Furthermore, STAT5 phosphorylation and cellular invasion induced in Prl stimulated cells were significantly reduced by using a Prl receptor antagonist that consists of Prl with four amino acid replacements. We conclude that Prl receptor is expressed at different levels in the majority of GBM tumors and that blocking of PrlR in U251-MG cells significantly reduce cellular invasion.

  • 28.
    Al-Rabadi, Laith Farah
    et al.
    Univ Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA..
    Caza, Tiffany
    Arkana Labs, Little Rock, AR USA..
    Trivin-Avillach, Claire
    Boston Med Ctr, Dept Med, Sect Nephrol, Rm 536,650 Albany St, Boston, MA 02118 USA.;Boston Univ, Sch Med, Boston, MA 02118 USA..
    Rodan, Aylin R.
    Univ Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA.;Univ Utah Hlth, Mol Med Program, Salt Lake City, UT USA.;Univ Utah Hlth, Dept Human Genet, Salt Lake City, UT USA.;Vet Affairs Salt Lake City Hlth Care Syst, Med Serv, Salt Lake City, UT USA..
    Andeen, Nicole
    Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA..
    Hayashi, Norifumi
    Boston Med Ctr, Dept Med, Sect Nephrol, Rm 536,650 Albany St, Boston, MA 02118 USA.;Boston Univ, Sch Med, Boston, MA 02118 USA.;Kanazawa Med Univ, Kanazawa, Ishikawa, Japan..
    Williams, Brandi
    Univ Utah Hlth, Moran Eye Ctr, Salt Lake City, UT USA..
    Revelo, Monica P.
    Univ Utah Hlth, Dept Pathol, Salt Lake City, UT USA..
    Clayton, Fred
    Univ Utah Hlth, Dept Pathol, Salt Lake City, UT USA..
    Abraham, Jo
    Univ Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA..
    Lin, Edwin
    Univ Utah Hlth, Dept Human Genet, Salt Lake City, UT USA..
    Liou, Willisa
    Univ Utah Hlth, Dept Pathol, Salt Lake City, UT USA..
    Zou, Chang-Jiang
    Univ Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA..
    Ramkumar, Nirupama
    Univ Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA..
    Cummins, Tim
    Univ Louisville, Dept Med, Div Nephrol & Hypertens, Clin Prote Lab,Sch Med, Louisville, KY USA..
    Wilkey, Daniel W.
    Univ Louisville, Dept Med, Div Nephrol & Hypertens, Clin Prote Lab,Sch Med, Louisville, KY USA..
    Kawalit, Issa
    Int Renal Care Assoc, Amman, Jordan..
    Herzog, Christian
    Univ Arkansas Med Sci, Internal Med Dept, Nephrol Div, Little Rock, AR USA..
    Storey, Aaron
    Univ Arkansas Med Sci, Internal Med Dept, Nephrol Div, Little Rock, AR USA..
    Edmondson, Rick
    Univ Arkansas Med Sci, Internal Med Dept, Nephrol Div, Little Rock, AR USA..
    Sjöberg, Ronald
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Yang, Tianxin
    Univ Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA.;Vet Affairs Salt Lake City Hlth Care Syst, Med Serv, Salt Lake City, UT USA..
    Chien, Jeremy
    Univ Calif Davis Hlth, Dept Biochem & Mol Med, Davis, CA USA..
    Merchant, Michael
    Univ Louisville, Dept Med, Div Nephrol & Hypertens, Clin Prote Lab,Sch Med, Louisville, KY USA..
    Arthur, John
    Univ Arkansas Med Sci, Internal Med Dept, Nephrol Div, Little Rock, AR USA..
    Klein, Jon
    Univ Louisville, Dept Med, Div Nephrol & Hypertens, Clin Prote Lab,Sch Med, Louisville, KY USA.;Robley Rex Vet Adm Med Ctr, Louisville, KY USA..
    Larsen, Chris
    Arkana Labs, Little Rock, AR USA..
    Beck, Laurence H.
    Boston Med Ctr, Dept Med, Sect Nephrol, Rm 536,650 Albany St, Boston, MA 02118 USA.;Boston Univ, Sch Med, Boston, MA 02118 USA..
    Serine Protease HTRA1 as a Novel Target Antigen in Primary Membranous Nephropathy2021In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 32, no 7, p. 1666-1681Article in journal (Refereed)
    Abstract [en]

    Background Identification of target antigens PLA2R, THSD7A, NELL1, or Semaphorin-3B can explain the majority of cases of primary membranous nephropathy (MN). However, target antigens remain unidentified in 15%-20% of patients. Methods A multipronged approach, using traditional and modern technologies, converged on a novel target antigen, and capitalized on the temporal variation in autoantibody titer for biomarker discovery. Immunoblotting of human glomerular proteins followed by differential immunoprecipitation and mass spectrometric analysis was complemented by laser-capture microdissection followed by mass spectrometry, elution of immune complexes from renal biopsy specimen tissue, and autoimmune profiling on a protein fragment microarray. Results These approaches identified serine protease HTRA1 as a novel podocyte antigen in a subset of patients with primary MN. Sera from two patients reacted by immunoblotting with a 51-kD protein within glomerular extract and with recombinant human HTRA1, under reducing and nonreducing conditions. Longitudinal serum samples from these patients seemed to correlate with clinical disease activity. As in PLA2R- and THSD7A- associated MN, anti-HTRA1 antibodies were predominantly IgG4, suggesting a primary etiology. Analysis of sera collected during active disease versus remission on protein fragment microarrays detected significantly higher titers of anti-HTRA1 antibody in active disease. HTRA1 was specifically detected within immune deposits of HTRA1-associated MN in 14 patients identified among three cohorts. Screening of 118 "quadruple-negative" (PLA2R-, THSD7A-, NELL1-, EXT2-negative) patients in a large repository of MN biopsy specimens revealed a prevalence of 4.2%. Conclusions Conventional and more modern techniques converged to identify serine protease HTRA1 as a target antigen in MN.

  • 29.
    Al-Saadi, Jonathan
    et al.
    Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A; Department of Neuroradiology, Karolinska University Hospital, 171 64, Stockholm, Sweden; MedTechLabs, Stockholm, Sweden.
    Waldén, Mathias
    Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A.
    Sandell, Mikael
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A; MedTechLabs, Stockholm, Sweden.
    Sohlmér, Jesper
    Department of Cell and Molecular Biology, Karolinska Institute, Solnavagen 9, 171 65 Stockholm, Sweden, Solnavägen 9.
    Grankvist, Rikard
    Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A.
    Friberger, Ida
    Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A.
    Andersson, Agneta
    Department of Medicine, Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden.
    Carlsten, Mattias
    Department of Medicine, Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden; Center for Cell Therapy and Allogeneic Stem Cell Transplantation, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden.
    Chien, Kenneth
    Department of Cell and Molecular Biology, Karolinska Institute, Solnavagen 9, 171 65 Stockholm, Sweden, Solnavägen 9.
    Lundberg, Johan
    Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A; Department of Neuroradiology, Karolinska University Hospital, 171 64, Stockholm, Sweden; MedTechLabs, Stockholm, Sweden.
    Witman, Nevin
    Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A.
    Holmin, Staffan
    Department of Clinical Neuroscience, Karolinska Institute, Tomtebodavagen 18A, 171 65 Stockholm, Sweden, Tomtebodavägen 18A; Department of Neuroradiology, Karolinska University Hospital, 171 64, Stockholm, Sweden; MedTechLabs, Stockholm, Sweden.
    Endovascular transplantation of mRNA-enhanced mesenchymal stromal cells results in superior therapeutic protein expression in swine heart2024In: Molecular therapy. Methods & clinical development, ISSN 2399-6951, E-ISSN 2329-0501, Vol. 32, no 2, article id 101225Article in journal (Refereed)
    Abstract [en]

    Heart failure has a poor prognosis and no curative treatment exists. Clinical trials are investigating gene- and cell-based therapies to improve cardiac function. The safe and efficient delivery of these therapies to solid organs is challenging. Herein, we demonstrate the feasibility of using an endovascular intramyocardial delivery approach to safely administer mRNA drug products and perform cell transplantation procedures in swine. Using a trans-vessel wall (TW) device, we delivered chemically modified mRNAs (modRNA) and mRNA-enhanced mesenchymal stromal cells expressing vascular endothelial growth factor A (VEGF-A) directly to the heart. We monitored and mapped the cellular distribution, protein expression, and safety tolerability of such an approach. The delivery of modRNA-enhanced cells via the TW device with different flow rates and cell concentrations marginally affect cell viability and protein expression in situ. Implanted cells were found within the myocardium for at least 3 days following administration, without the use of immunomodulation and minimal impact on tissue integrity. Finally, we could increase the protein expression of VEGF-A over 500-fold in the heart using a cell-mediated modRNA delivery system compared with modRNA delivered in saline solution. Ultimately, this method paves the way for future research to pioneer new treatments for cardiac disease.

  • 30. Altai, M.
    et al.
    Honarvar, H.
    Wallberg, H.
    Strand, J.
    Varasteh, Z.
    Orlova, A.
    Dunas, F.
    Sandstrom, M.
    Rosestedt, M.
    Löfblom, John
    KTH, School of Biotechnology (BIO), Protein Technology.
    Tolmachev, V.
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Protein Technology.
    Selection of an optimal cysteine-containing peptide-based chelator for labeling of Affibody molecules with Re-1882013In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, p. S219-S220Article in journal (Other academic)
  • 31.
    Altai, M.
    et al.
    Uppsala Univ, Imuunol Genet & Pathol, Uppsala, Sweden..
    Liu, Hao
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, Div Prot Technol, Stockholm, Sweden..
    Orlova, A.
    Div Mol Imaging, Dept Med Chem, Uppsala, Sweden..
    Tolmachev, V.
    Uppsala Univ, Imuunol Genet & Pathol, Uppsala, Sweden..
    Gräslund, Torbjörn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, Div Prot Technol, Stockholm, Sweden..
    Improving of molecular design of a novel Affibody-fused HER2-recognising anticancer toxin using radionuclide-based techniques2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, p. S178-S178Article in journal (Other academic)
  • 32. Altai, M.
    et al.
    Perols, Anna
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Sandström, M.
    Boschetti, F.
    Orlova, A.
    Tolmachev, V.
    Evaluation of a maleimido derivative of NODAGA for site-specific In-111-labeling of Affibody molecules2011In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 38, p. S146-S146Article in journal (Other academic)
  • 33. Altai, M.
    et al.
    Strand, J.
    Rosik, Daniel
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Selvaraju, R.
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Orlova, A.
    Tolmachev, V.
    Comparative evaluation of anti-HER2 affibody molecules labeled with 68Ga and 111In using maleimido derivatives of DOTA and NODAGA.2012In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 39, p. S299-S299Article in journal (Refereed)
  • 34.
    Altai, M.
    et al.
    Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden..
    Vorobyeva, A.
    Myrhammar, Anders
    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.
    Yoneoka, S.
    Lab Adv Nucl Energy, Tokyo, Japan..
    Tsukahara, T.
    Lab Adv Nucl Energy, Tokyo, Japan..
    Eriksson Karlström, Amelie
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Orlova, A.
    Dept Med Chem, Uppsala, Sweden..
    Tolmachev, V.
    Design and evaluation oflactosaminated cetuximabas a clearing agent for antibody-based PNA-mediated pretargeting2020In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 47, no SUPPL 1, p. S343-S344Article in journal (Other academic)
  • 35. Altai, M.
    et al.
    Wallberg, H.
    Honarvar, H.
    Strand, J.
    Orlova, A.
    Löfblom, John
    KTH, School of Biotechnology (BIO), Protein Technology.
    Varasteh, Z.
    Sandström, M.
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Protein Technology.
    Tolmachev, V.
    Re-188-Z(HER2: V2), a promising targeting agent against HER2-expressing tumors: in vitro and in vivo assessment2013In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, p. S119-S119Article in journal (Other academic)
  • 36.
    Altai, M.
    et al.
    Inst Immunol Genet & Pathol, Uppsala, Sweden..
    Westerlund, Kristina
    KTH, School of Biotechnology (BIO), Protein Technology.
    Konijnenberg, M.
    Erasmus MC, Dept Nucl Med & Radiol, Rotterdam, Netherlands..
    Mitran, B.
    Div Mol Imaging, Uppsala, Sweden..
    Oroujeni, M.
    Inst Immunol Genet & Pathol, Uppsala, Sweden..
    de Jong, M.
    Erasmus MC, Dept Nucl Med & Radiol, Rotterdam, Netherlands..
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Protein Technology.
    Orlova, A.
    Div Mol Imaging, Uppsala, Sweden..
    Tolmachev, V.
    Inst Immunol Genet & Pathol, Uppsala, Sweden..
    Pretargeted radionuclide therapy of HER2-expressing SKOV-3 human xenografts using an Affibody molecule-based PNA-mediated pretargeting2017In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 44, p. S142-S142Article in journal (Other academic)
  • 37. Altai, M.
    et al.
    Westerlund, Kristina
    KTH, School of Biotechnology (BIO), Protein Technology.
    Velletta, J.
    Mitran, B.
    Honarvar, H.
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Protein Technology.
    Evaluation of affibody molecule-based PNA-mediated radionuclide pretargeting: Development of an optimized conjugation protocol and 177Lu labeling2017In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 54, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Introduction We have previously developed a pretargeting approach for affibody-mediated cancer therapy based on PNA–PNA hybridization. In this article we have further developed this approach by optimizing the production of the primary agent, ZHER2:342-SR-HP1, and labeling the secondary agent, HP2, with the therapeutic radionuclide 177Lu. We also studied the biodistribution profile of 177Lu-HP2 in mice, and evaluated pretargeting with 177Lu-HP2 in vitro and in vivo. Methods The biodistribution profile of 177Lu-HP2 was evaluated in NMRI mice and compared to the previously studied 111In-HP2. Pretargeting using 177Lu-HP2 was studied in vitro using the HER2-expressing cell lines BT‐474 and SKOV-3, and in vivo in mice bearing SKOV-3 xenografts. Results and conclusion Using an optimized production protocol for ZHER2:342-SR-HP1 the ligation time was reduced from 15 h to 30 min, and the yield increased from 45% to 70%. 177Lu-labeled HP2 binds specifically in vitro to BT474 and SKOV-3 cells pre-treated with ZHER2:342-SR-HP1. 177Lu-HP2 was shown to have a more rapid blood clearance compared to 111In-HP2 in NMRI mice, and the measured radioactivity in blood was 0.22 ± 0.1 and 0.68 ± 0.07%ID/g for 177Lu- and 111In-HP2, respectively, at 1 h p.i. In contrast, no significant difference in kidney uptake was observed (4.47 ± 1.17 and 3.94 ± 0.58%ID/g for 177Lu- and 111In-HP2, respectively, at 1 h p.i.). Co-injection with either Gelofusine or lysine significantly reduced the kidney uptake for 177Lu-HP2 (1.0 ± 0.1 and 1.6 ± 0.2, respectively, vs. 2.97 ± 0.87%ID/g in controls at 4 h p.i.). 177Lu-HP2 accumulated in SKOV-3 xenografts in BALB/C nu/nu mice when administered after injection of ZHER2:342-SR-HP1. Without pre-injection of ZHER2:342-SR-HP1, the uptake of 177Lu-HP2 was about 90-fold lower in tumor (0.23 ± 0.08 vs. 20.7 ± 3.5%ID/g). The tumor-to-kidney radioactivity accumulation ratio was almost 5-fold higher in the group of mice pre-injected with ZHER2:342-SR-HP1. In conclusion, 177Lu-HP2 was shown to be a promising secondary agent for affibody-mediated tumor pretargeting in vivo.

  • 38. Altai, Mohamed
    et al.
    Perols, Anna
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Sandström, Mattias
    Boschetti, Frederic
    Orlova, Anna
    Tolmachev, Vladimir
    Preclinical evaluation of anti-HER2 Affibody molecules site-specifically labeled with In-111 using a maleimido derivative of NODAGA2012In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 39, no 4, p. 518-529Article in journal (Refereed)
    Abstract [en]

    Introduction: Affibody molecules have demonstrated potential for radionuclide molecular imaging. The aim of this study was to synthesize and evaluate a maleimido derivative of the 1,4,7-triazacyclononane-l-glutaric acid-4,7-diacetic acid (NODAGA) for site-specific labeling of anti-HER2 Affibody molecule. Methods: The maleimidoethylmonoamide NODAGA (MMA-NODAGA) was synthesized and conjugated to Z(HER2:2395) Affibody molecule having a C-terminal cysteine. Labeling efficiency, binding specificity to and cell internalization by HER2-expressing cells of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) were studied. Biodistribution of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) and [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) was compared in mice. Results: The affinity of [MMA-NODAGA-Cys(61)]-Z(HER2:2395) binding to HER2 was 67 pM. The In-1111-labeling yield was 99.6%+/- 0.5% after 30 min at 60 degrees C. [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) bound specifically to HER2-expressing cells in vitro and in vivo. Tumor uptake of [In-111-MMA-NODAGA-Cys(61)]-ZHER(2:2395) in mice bearing DU-145 xenografts (4.7%+/- 0.8% ID/g) was lower than uptake of [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) (7.5%+/- 1.6% ID/g). However, tumor-to-organ ratios were higher for [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) due to higher clearance rate from normal tissues. Conclusions: MMA-NODAGA is a promising chelator for site-specific labeling of targeting proteins containing unpaired cysteine. Appreciable influence of chelators on targeting properties of Affibody molecules was demonstrated.

  • 39. Altai, Mohamed
    et al.
    Perols, Anna
    KTH, School of Biotechnology (BIO), Protein Technology.
    Tsourma, Maria
    Mitran, Bogdan
    Honarvar, Hadis
    Robillard, Marc
    Rossin, Raffaella
    ten Hoeve, Wolter
    Lubberink, Mark
    Orlova, Anna
    Karlström, Amelie Eriksson
    KTH, School of Biotechnology (BIO), Protein Technology.
    Tolmachev, Vladimir
    Feasibility of Affibody-Based Bioorthogonal Chemistry Mediated Radionuclide Pretargeting2016In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 57, no 3, p. 431-436Article in journal (Refereed)
    Abstract [en]

    Affibody molecules constitute a new class of probes for radionuclide tumor targeting. The small size of Affibody molecules is favorable for rapid localization in tumors and clearance from circulation. However, high renal reabsorption of Affibody molecules prevents the use of residualizing radiometals, including several promising low-energy (beta- and alpha-emitters, for radionuclide therapy. We tested a hypothesis that Affibody-based pretargeting mediated by a bioorthogonal interaction between trans-cyclooctene (TCO) and tetrazine would provide higher accumulation of radiometals in tumor xenografts than in the kidneys. Methods: TCO was conjugated to the anti-human epidermal growth factor receptor 2 (HER2) Affibody molecule Z(2395). DOTA-tetrazine was labeled with In-111 and Lu-177. In vitro pretargeting was studied in HER2-expressing SKOV-3 and BT474 cell lines. In vivo studies were performed on BALB/C nu/nu mice bearing SKOV-3 xenografts. Results: I-125-Z(2395)-TCO bound specifically to HER2-expressing cells in vitro with an affinity of 45 +/- 16 pM. In-111-tetrazine bound specifically and selectively to Z(2325)-TCO pretreated cells. In vivo studies demonstrated HER2-specific I-125-Z(2395)-TCO accumulation in xenografts. TCO-mediated In-111-tetrazine localization was shown in tumors, when the radiolabeled tracer was injected 4 h after an injection of Z(2395)-TCO. At 1 h after injection, the tumor uptake of In-111-tetrazine and Lu-177-tetrazine was approximately 2-fold higher than the renal uptake. Pretargeting provided more than a 56-fold reduction of renal uptake of In-111 in comparison with direct targeting. Conclusion: The feasibility of Affibody-based bioorthogonal chemistry-mediated pretargeting was demonstrated. The use of pre-targeting provides a substantial reduction of radiometal accumulation in kidneys, creating preconditions for palliative radionuclide therapy.

  • 40. Altai, Mohamed
    et al.
    Wållberg, Helena
    KTH, School of Biotechnology (BIO), Protein Technology.
    Honarvar, Hadis
    Strand, Joanna
    Orlova, Anna
    Varasteh, Zohreh
    Sandström, Mattias
    Löfblom, John
    KTH, School of Biotechnology (BIO), Protein Technology.
    Larsson, Erik
    Strand, Sven-Erik
    Lubberink, Mark
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Protein Technology. Uppsala University, Sweden.
    Tolmachev, Vladimir
    Re-188-Z(HER2:V2), a Promising Affibody-Based Targeting Agent Against HER2-Expressing Tumors: Preclinical Assessment2014In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 55, no 11, p. 1842-1848Article in journal (Refereed)
    Abstract [en]

    Affibody molecules are small (7 kDa) nonimmunoglobulin scaffold proteins with favorable tumor-targeting properties. Studies concerning the influence of chelators on biodistribution of Tc-99m-labeled Affibody molecules demonstrated that the variant with a C-terminal glycyl-glycyl-glycyl-cysteine peptide-based chelator (designated Z(HER2:V2)) has the best biodistribution profile in vivo and the lowest renal retention of radioactivity. The aim of this study was to evaluate Re-188-Z(HER2:v2) as a potential candidate for radionuclide therapy of human epidermal growth factor receptor type 2 (HER2)-expressing tumors. Methods: Z(HER2:V2) was labeled with Re-188 using a gluconate-containing kit. Targeting of HER2-overexpressing SKOV-3 ovarian carcinoma xenografts in nude mice was studied for a dosimetry assessment. Results: Binding of Re-188-Z(HER2:V2) to living SKOV-3 cells was demonstrated to be specific, with an affinity of 6.4 +/- 0.4 pM. The biodistribution study showed a rapid blood clearance (1.4 +/- 0.1 percentage injected activity per gram [%ID/g] at 1 h after injection). The tumor uptake was 14 +/- 2, 12 +/- 2, 5 +/- 2, and 1.8 +/- 0.5 %IA/g at 1, 4, 24, and 48 h after injection, respectively. The in vivo targeting of HER2-expressing xenografts was specific. Already at 4 h after injection, tumor uptake exceeded kidney uptake (2.1 +/- 0.2 %IA/g). Scintillation-camera imaging showed that tumor xenografts were the only sites with prominent accumulation of radioactivity at 4 h after injection. Based on the biokinetics, a dosimetry evaluation for humans suggests that Re-188-Z(HER2:v2) would provide an absorbed dose to tumor of 79 Gy without exceeding absorbed doses of 23 Gy to kidneys and 2 Gy to bone marrow. This indicates that future human radiotherapy studies may be feasible. Conclusion: (188)ReZ(HER2:v2) can deliver high absorbed doses to tumors without exceeding kidney and bone marrow toxicity limits.

  • 41.
    Altay, Özlem
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Mohammadi, Elyas
    KTH, Centres, Science for Life Laboratory, SciLifeLab. Ferdowsi Univ Mashhad, Dept Anim Sci, Mashhad 9177948974, Razavi Khorasan, Iran..
    Lam, Simon
    Kings Coll London, Ctr Host Microbiome Interact, Fac Dent Oral & Craniofacial Sci, London SE1 9RT, England..
    Turkez, Hasan
    Ataturk Univ, Dept Med Biol, Fac Med, TR-25240 Erzurum, Turkey..
    Boren, Jan
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Mol & Clin Med, Wallenberg Lab, S-41345 Gothenburg, Sweden..
    Nielsen, Jens
    Chalmers Univ Technol, Dept Biol & Biol Engn, S-41296 Se Gothenburg, Sweden..
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Mardinoglu, Adil
    KTH, Centres, Science for Life Laboratory, SciLifeLab. Kings Coll London, Ctr Host Microbiome Interact, Fac Dent Oral & Craniofacial Sci, London SE1 9RT, England..
    Current Status of COVID-19 Therapies and Drug Repositioning Applications2020In: iScience, E-ISSN 2589-0042 , Vol. 23, no 7, article id 101303Article, review/survey (Refereed)
    Abstract [en]

    The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in silico studies of drug development efforts against SARS-CoV-2.

  • 42.
    Alvez, Maria Bueno
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Edfors, Fredrik
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    von Feilitzen, Kalle
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Zwahlen, Martin
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Mardinoglu, Adil
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, SE1 9RT, UK.
    Edqvist, Per Henrik
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Sjöblom, Tobias
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Lundin, Emma
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Rameika, Natallia
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Enblad, Gunilla
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Lindman, Henrik
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Höglund, Martin
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Hesselager, Göran
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Stålberg, Karin
    Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
    Enblad, Malin
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Simonson, Oscar E.
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Häggman, Michael
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Axelsson, Tomas
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Åberg, Mikael
    Department of Medical Sciences, Clinical Chemistry and SciLifeLab Affinity Proteomics, Uppsala University, Uppsala, Sweden.
    Nordlund, Jessica
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Zhong, Wen
    Science for Life Laboratory, Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden.
    Karlsson, Max
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Gyllensten, Ulf
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Ponten, Fredrik
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Fagerberg, Linn
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Next generation pan-cancer blood proteome profiling using proximity extension assay2023In: Nature Communications, E-ISSN 2041-1723, Vol. 14, no 1, article id 4308Article in journal (Refereed)
    Abstract [en]

    A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.

  • 43. Ambikan, Anoop T.
    et al.
    Elaldi, Nazif
    Svensson-Akusjärvi, Sara
    Bagci, Binnur
    Pektas, Ayse Nur
    Hewson, Roger
    United Kingdom Health Security Agency, Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom.
    Bagci, Gokhan
    Arasli, Mehmet
    Appelberg, Sofia
    Mardinoglu, Adil
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Sood, Vikas
    Végvári, Ákos
    Benfeitas, Rui
    Gupta, Soham
    Cetin, Ilhan
    Mirazimi, Ali
    Neogi, Ujjwal
    Systems-level temporal immune-metabolic profile in Crimean-Congo hemorrhagic fever virus infection2023In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 120, no 37Article in journal (Refereed)
    Abstract [en]

    Crimean-Congo hemorrhagic fever (CCHF) caused by CCHF virus (CCHFV) is one of the epidemic-prone diseases prioritized by the World Health Organisation as public health emergency with an urgent need for accelerated research. The trajectory of host response against CCHFV is multifarious and remains unknown. Here, we reported the temporal spectrum of pathogenesis following the CCHFV infection using genome-wide blood transcriptomics analysis followed by advanced systems biology analysis, temporal immune-pathogenic alterations, and context-specific progressive and postinfection genome-scale metabolic models (GSMM) on samples collected during the acute (T0), early convalescent (T1), and convalescent-phase (T2). The interplay between the retinoic acid-inducible gene-I-like/nucleotide-binding oligomerization domain-like receptor and tumor necrosis factor signaling governed the trajectory of antiviral immune responses. The rearrangement of intracellular metabolic fluxes toward the amino acid metabolism and metabolic shift toward oxidative phosphorylation and fatty acid oxidation during acute CCHFV infection determine the pathogenicity. The upregulation of the tricarboxylic acid cycle during CCHFV infection, compared to the noninfected healthy control and between the severity groups, indicated an increased energy demand and cellular stress. The upregulation of glycolysis and pyruvate metabolism potentiated energy generation through alternative pathways associated with the severity of the infection. The downregulation of metabolic processes at the convalescent phase identified by blood cell transcriptomics and single-cell type proteomics of five immune cells (CD4+ and CD8+ T cells, CD14+ monocytes, B cells, and NK cells) potentially leads to metabolic rewiring through the recovery due to hyperactivity during the acute phase leading to post-viral fatigue syndrome.

  • 44.
    Amin, Nuhu
    et al.
    Int Ctr Diarrhoeal Dis Res Bangladesh Icddr B, Infect Dis Div, Dhaka, Bangladesh.;Univ Technol Sydney, Inst Sustainable Futures, 235 Jones St, Ultimo, NSW 2007, Australia..
    Haque, Rehnuma
    Int Ctr Diarrhoeal Dis Res Bangladesh Icddr B, Infect Dis Div, Dhaka, Bangladesh.;Stanford Univ, Sch Med, Stanford, CA USA..
    Rahman, Md. Ziaur
    Int Ctr Diarrhoeal Dis Res Bangladesh Icddr B, Infect Dis Div, Dhaka, Bangladesh..
    Rahman, Mohammed Ziaur
    Int Ctr Diarrhoeal Dis Res Bangladesh Icddr B, Infect Dis Div, Dhaka, Bangladesh..
    Mahmud, Zahid Hayat
    Int Ctr Diarrhoeal Dis Res Bangladesh Icddr B, Infect Dis Div, Dhaka, Bangladesh..
    Hasan, Rezaul
    Int Ctr Diarrhoeal Dis Res Bangladesh Icddr B, Infect Dis Div, Dhaka, Bangladesh..
    Islam, MD Tahmidul
    KTH, School of Architecture and the Built Environment (ABE), Sustainable development, Environmental science and Engineering. WaterAid, Dhaka, Bangladesh..
    Sarker, Protim
    Int Ctr Diarrhoeal Dis Res Bangladesh Icddr B, Infect Dis Div, Dhaka, Bangladesh..
    Sarker, Supriya
    Directorate Gen Hlth Serv DGHS, Dhaka, Bangladesh..
    Adnan, Shaikh Daud
    Directorate Gen Hlth Serv DGHS, Dhaka, Bangladesh..
    Akter, Nargis
    UNICEF, Water Sanitat & Hyg WASH Sect, Dhaka, Bangladesh..
    Johnston, Dara
    UNICEF, Water Sanitat & Hyg WASH Sect, Dhaka, Bangladesh..
    Rahman, Mahbubur
    Int Ctr Diarrhoeal Dis Res Bangladesh Icddr B, Infect Dis Div, Dhaka, Bangladesh.;Inst Epidemiol Dis Control & Res IEDCR, Dhaka, Bangladesh..
    Liu, Pengbo
    Emory Univ, Ctr Global Safe Water Sanitat & Hyg, Atlanta, GA USA..
    Wang, Yuke
    Emory Univ, Ctr Global Safe Water Sanitat & Hyg, Atlanta, GA USA..
    Shirin, Tahmina
    Inst Epidemiol Dis Control & Res IEDCR, Dhaka, Bangladesh..
    Bhattacharya, Prosun
    KTH, School of Architecture and the Built Environment (ABE), Sustainable development, Environmental science and Engineering, Water and Environmental Engineering.
    Dependency of sanitation infrastructure on the discharge of faecal coliform and SARS-CoV-2 viral RNA in wastewater from COVID and non-COVID hospitals in Dhaka, Bangladesh2023In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 867, article id 161424Article in journal (Refereed)
    Abstract [en]

    The detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA in wastewater can be used as an indicator of the presence of SARS-CoV-2 infection in specific catchment areas. We conducted a hospital-based study to explore wastewater management in healthcare facilities and analyzed SARS-CoV-2 RNA in the hospital wastewater in Dhaka city during the Coronavirus disease (COVID-19) outbreak between September 2020-January 2021. We selected three COVID-hospitals, two non-COVID-hospitals, and one non-COVID-hospital with COVID wards, conducted spot-checks of the sanitation systems (i.e., toilets, drainage, and septic-tank), and collected 90 untreated wastewater effluent samples (68 from COVID and 22 from non-COVID hospitals). E. coli was detected using a membrane filtration technique and reported as colony forming unit (CFU). SARS-CoV-2 RNA was detected using the iTaq Universal Probes One-Step kit for RT-qPCR amplification of the SARS-CoV-2 ORF1ab and N gene targets and quantified for SARS-CoV-2 genome equivalent copies (GEC) per mL of sample. None of the six hospitals had a primary wastewater treatment facility; two COVID hospitals had functional septic tanks, and the rest of the hospitals had either broken onsite systems or no containment of wastewater. Overall, 100 % of wastewater samples were positive with a high concentration of E.coli (mean = 7.0 log10 CFU/100 mL). Overall, 67 % (60/90) samples were positive for SARS-CoV-2. The highest SARS-CoV-2 concentrations (median: 141 GEC/mL; range: 13-18,214) were detected in wastewater from COVID-hospitals, and in non-COVID-hospitals, the median SARS-CoV-2 concentration was 108 GEC/mL (range: 30-1829). Our results indicate that high concentrations of E. coli and SARS-CoV-2 were discharged through the hospital wastewa-ter (both COVID and non-COVID) without treatment into the ambient water bodies. Although there is no evidence for transmission of SARS-CoV-2 via wastewater, this study highlights the significant risk posed by wastewater from health care facilities in Dhaka for the many other diseases that are spread via faecal oral route. Hospitals in low-income settings could function as sentinel sites to monitor outbreaks through wastewater-based epidemiological surveillance systems. Hospitals should aim to adopt the appropriate wastewater treatment technologies to reduce the discharge of pathogens into the environment and mitigate environmental exposures.

  • 45.
    Amin, Nuhu
    et al.
    Icddr, Dhaka, Bangladesh..
    Haque, Rehnuma
    Icddr, Dhaka, Bangladesh..
    Rahman, Md. Ziaur
    Icddr, Dhaka, Bangladesh..
    Rahman, Mohammed Ziaur
    Icddr, Dhaka, Bangladesh..
    Mahmud, Zahid Hayat
    Icddr, Dhaka, Bangladesh..
    Hasan, Rezaul
    Icddr, Dhaka, Bangladesh..
    Sarker, Supriya
    Directorate Gen Hlth Serv DGHS, Dhaka, Bangladesh..
    Akter, Nargis
    UNICEF, Dhaka, Bangladesh..
    Johnston, Dara
    UNICEF, Dhaka, Bangladesh..
    Rahman, Mahbubur
    Icddr, Dhaka, Bangladesh..
    Bhattacharya, Prosun
    KTH, School of Architecture and the Built Environment (ABE), Sustainable development, Environmental science and Engineering, Water and Environmental Engineering.
    Hospitals In Dhaka And Discharge Of Wastewater With High Sars-Cov-2 Viral Rna Genetic Loadings: An Assessment Of Potential Environmental Health Risk2021In: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, E-ISSN 1476-1645, Vol. 105, no 5, p. 265-266Article in journal (Other academic)
  • 46.
    Amini, Mehdi
    et al.
    the Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, Switzerland.
    Mostafaei, Shayan
    the Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
    Poursamimi, Mohamad
    the Department of Medical Physics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
    Chatterjee, Saikat
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Information Science and Engineering.
    Mansouri, Zahra
    the Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, Switzerland.
    Ghorbani, Mehdi
    the Department of Biomedical Engineering and Medical Physics, Shahid Beheshti University of medical sciences, Tehran, Iran.
    Shiri, Isaac
    the Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, Switzerland.
    Zaidi, Habib
    the Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, Switzerland; Geneva University Neurocenter, Geneva University, CH-1205 Geneva, Switzerland; Department of Nuclear Medicine and Molecular Imaging, University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University of Groningen; University Medical Center Groningen, 9700 RB Groningen, Netherlands; Department of Nuclear Medicine, University of Southern Denmark, DK-500, Odense, Denmark..
    Interpretable PET/CT Radiomic Based Prognosis Modeling of NSCLC Recurrent Following Complete Resection2022In: 2022 IEEE NSS/MIC RTSD - IEEE Nuclear Science Symposium, Medical Imaging Conference and Room Temperature Semiconductor Detector Conference, Institute of Electrical and Electronics Engineers (IEEE) , 2022Conference paper (Refereed)
    Abstract [en]

    This study aimed to develop an interpretable prognostic model with a nomogram for Non-Small Cell Lung Cancer (NSCLC) recurrence prediction following complete resection, using multi-modality PET/CT fusion radiomics and patients' clinical features. Retrospectively, 181 NSCLC patients who had undergone18F-FDG PET/CT scan were enrolled and split into training (2/3) and testing (1/3) partitions. Before image fusion, PET and CT images were registered, resized to equal isotropic voxel size, and clipped and normalized. Guided Filtering Fusion GFF algorithm was used for image fusion. Two hundred eighteen radiomic features were extracted from each PET, CT, and fused image, including morphological, first-order statistical, and texture features. Clinical features included age, sex, smoking status, weight, radiation, chemotherapy, pathological stage, etc. Feature selection and univariate and multivariate modeling were performed using the CoxBoost algorithm. Harrell's Concordance index (C-index) was used to evaluate the performance of the models, and compare C test was used to statistically compare the performance of the models (p-values < 0.05 were considered significant). Clinical, Clinical+PET, Clinical+CT, and Clinical+GFF resulted in c-indices (confidence interval) of 0.701 (0.589-0.812), 0.757 (0.647-0.867), 0.706 (0.607, 0.807), and 0.824 (0.751-0.896), respectively. Statistical comparison of the performance of different models with the Clinical model revealed that while PET and GFF features can significantly increase the performance (p-values 0.009 and 0.001, respectively), CT features did not significantly improve the performance of the Clinical model (p-value 0.279). Therefore, the nomogram was developed based on the Clinical+GFF model (with the best performance). Radiomic features extracted from PET and PET/CT fusion images can improve the recurrence prognosis in NSCLC patients compared to the conventional clinical factors alone.

  • 47.
    Amjadimanesh, Hossein
    et al.
    School of Mechanical Engineering, Shiraz University, Shiraz, 71345, Iran.
    Faramarzi, Mohammad
    Department of Otolaryngology Head and Neck Surgery, Shiraz University of Medical Science, Shiraz, 71348, Iran.
    Sadrizadeh, Sasan
    KTH, School of Architecture and the Built Environment (ABE), Civil and Architectural Engineering, Sustainable Buildings. Department for Sustainable Environment and Community Development, Mälardalens University, Västerås, 72123, Sweden.
    Abouali, Omid
    KTH, School of Architecture and the Built Environment (ABE), Civil and Architectural Engineering. School of Mechanical Engineering, Shiraz University, Shiraz, 71345, Iran.
    Micro-particle deposition in maxillary sinus for various sizes of opening in a virtual endoscopic surgery2023In: Experimental and Computational Multiphase Flow, ISSN 2661-8869, Vol. 5, no 3, p. 262-271Article in journal (Refereed)
    Abstract [en]

    Treatment of sinusitis by surgical procedures is recommended only when medication therapies fail to relieve sinusitis symptoms. In this study, a realistic 3D model of the human upper airway system was constructed based on CT images of an adult male and three different virtual functional endoscopic sinus surgeries (FESS), including only uncinectomy and uncinectomy with two different sizes of Middle Meatal Antrostomy (MMA) performed on that model. Airflow and deposition of micro-particles in the range of 1–30 µm were numerically simulated in the postoperative cases for rest and moderate activity breathing conditions. The results showed that the uncinate process alone protects the maxillary sinus well against the entry of micro-particles, and its removal by uncinectomy allows particles to deposit on the sinus wall easily. Generally, uncinectomy with a degree of MMA increases the number of deposited particles in the maxillary sinuses compared to uncinectomy surgery alone. In the studied models, the highest particle deposition in the maxillary sinuses occurred among particles with a diameter of 10–20 µm. Also, if a person inhales particles during rest breathing conditions at a low respiratory rate, the number of particles deposited in the sinuses increases. [Figure not available: see fulltext.]

  • 48.
    Amjadimanesh, Hossein
    et al.
    Shiraz Univ, Sch Mech Engn, Shiraz, Iran..
    Norouzi, Mohammad
    Shiraz Univ, Sch Mech Engn, Shiraz, Iran..
    Johnson, Matthew S.
    Univ Copenhagen, Dept Chem, Copenhagen, Denmark..
    Sadrizadeh, Sasan
    KTH, School of Architecture and the Built Environment (ABE), Civil and Architectural Engineering, Sustainable Buildings.
    Abouali, Omid
    KTH, School of Architecture and the Built Environment (ABE), Civil and Architectural Engineering. Shiraz Univ, Sch Mech Engn, Shiraz, Iran..
    The effect of body position while coughing on the airborne transmission of pathogens2022In: Physics of fluids, ISSN 1070-6631, E-ISSN 1089-7666, Vol. 34, no 4, p. 041902-, article id 041902Article in journal (Refereed)
    Abstract [en]

    Given the recent acceptance of the central role of airborne transmission for SARS-CoV-2, increased attention has been paid to the dispersion of respiratory droplets in different scenarios. Studies including numerical simulations have been conducted on methods for breaking the chains of transmission. Here, we present the first such study on the impact of body position while coughing on the dispersion of respiratory droplets. Four scenarios are examined, including normal standing, bending the head at different angles, coughing into the elbow in still air, and a gentle breeze from the front and behind. The model showed that an uncovered cough is dangerous and causes many droplets to enter the environment, posing a cross-contamination threat to the others. Droplets with an initial diameter smaller than 62.5 mu m remain suspended in windless air for more than 3 min. In the presence of wind, these droplets move with the wind flow and may travel long distances greater than 3.5 m. The model showed that covering the mouth with the elbow while coughing is clearly the best strategy for reducing airborne transmission of exhaled pathogens. About 62% of the initial number of droplets deposit on the cougher's elbow immediately after the cough and have no chance of spreading through the air in both windless and windy conditions. Covering the cough in windless or light breeze conditions also causes the upward thermal plume around the body to expel many small droplets.

  • 49.
    Anderlind, Eva
    et al.
    KTH, School of Computer Science and Communication (CSC), Human - Computer Interaction, MDI.
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Sallnäs Pysander, Eva-Lotta
    KTH, School of Computer Science and Communication (CSC), Numerical Analysis and Computer Science, NADA.
    Lind, Bengt K.
    Karolinska Institute, Department of Medical Radiation Physics.
    Maguire, Gerald Q. Jr.
    KTH, School of Information and Communication Technology (ICT), Communication Systems, CoS.
    Will haptic feedback speed up medical imaging? An application to radiation treatment planning2008In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 47, no 1, p. 32-37Article in journal (Refereed)
    Abstract [en]

    Haptic technology enables us to incorporate the sense of touch into computer applications, providing an additional input/output channel. The purpose of this study was to examine if haptic feedback can help physicians and other practitioners to interact with medical imaging and treatment planning systems. A haptic application for outlining target areas (a key task in radiation therapy treatment planning) was implemented and then evaluated via a controlled experiment with ten subjects. Even though the sample size was small, and the application only a prototype, results showed that haptic feedback can significantly increase (p0.05) the speed of outlining target volumes and organs at risk. No significant differences were found regarding precision or perceived usability. This promising result warrants further development of a full haptic application for this task. Improvements to the usability of the application as well as to the forces generated have been implemented and an experiment with more subjects is planned.

  • 50.
    Anderlind, Eva
    et al.
    KTH, School of Computer Science and Communication (CSC), Human - Computer Interaction, MDI.
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Sallnäs Pysander, Eva-Lotta
    KTH, School of Computer Science and Communication (CSC), Human - Computer Interaction, MDI.
    Maguire Jr., Gerald Q.
    KTH, School of Information and Communication Technology (ICT), Communication Systems, CoS.
    Lind, Bengt K.
    Karolinska Institute, Medical Radiation Physics.
    The value of haptic feedback in medical imaging and treatment planning2006In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 81, p. 1277-Article in journal (Refereed)
1234567 1 - 50 of 1984
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