Author: "Paul van der Valk" - Searchworks@Jio Institute Digital Library Search Results

290 results on '"Paul van der Valk"'

251. Tissue distribution and induction of human multidrug resistant protein 3

Author: Ronald P.J. Oude Elferink, Diederik K Bosman, J.Marleen L. De Vree, Rik J. Scheper, Paul van der Valk, Adriana C L M Pijnenborg, Piet Borst, Marcel Kool, Marcel de Haas, George L. Scheffer, Oncogenomics, General Paediatrics, Tytgat Institute for Liver and Intestinal Research, Gastroenterology and Hepatology, and Other departments
Subjects: Pathology, medicine.medical_specialty, Cholestasis, Gallbladder, Multidrug resistance-associated protein 2, Blotting, Western, Progressive familial intrahepatic cholestasis, Cell Biology, Biology, medicine.disease, Immunohistochemistry, Pathology and Forensic Medicine, medicine.anatomical_structure, Neoplasms, medicine, Humans, Multidrug Resistance-Associated Proteins, Pancreas, Molecular Biology, Enterohepatic circulation, Bile circulation
Abstract: The multidrug resistance protein (MRP) family consists of several members and, for some of these transporter proteins, distinct roles in multidrug resistance and normal tissue functions have been well established (MRP1 and MRP2) or are still under investigation (MRP3). MRP3 expression studies in human tissues have been largely restricted to the mRNA level. In this report we extended these studies and further explored MRP3 expression at the protein level. Western blot and immunohistochemistry with two MRP3-specific monoclonal antibodies, M(3)II-9 and M(3)II-21, showed MRP3 protein to be present in adrenal gland, and kidney and in tissues of the intestinal tract: colon, pancreas, gallbladder, and liver. In epithelia, MRP3 was found to be located at the basolateral sides of cell membranes. In normal liver, MRP3 was detected at lower levels than anticipated from the mRNA data and was found present mainly in the bile ducts. In livers from patients with various forms of cholestasis, MRP3 levels were frequently increased in the proliferative cholangiocytes, with sometimes additional staining of the basolateral membranes of the hepatocytes. This was especially evident in patients with type 3 progressive familial intrahepatic cholestasis. The present results support the view that MRP3 plays a role in the cholehepatic and enterohepatic circulation of bile and in protection within the biliary tree and tissues along the bile circulation route against toxic bile constituents. The possible functional roles for MRP3 in the adrenal gland and in the kidney remain as yet unknown. In a panel of 34 tumor samples of various histogenetic origins, distinct amounts of MRP3 were detected in a limited number of cases, including lung, ovarian, and pancreatic cancers. These findings may be of potential clinical relevance when considering the drug treatment regimens for these tumor types.
Published: 2002

252. Gene therapy for meningioma: improved gene delivery with targeted adenoviruses

Author: Angelique M. Leonhart, Martine L.M. Lamfers, David T. Curiel, W. Peter Vandertop, Paul van der Valk, Jacques Grill, Hidde J. Haisma, Victor W. van Beusechem, Winald R. Gerritsen, Clemens M F Dirven, Herbert M. Pinedo, Neurosurgery, Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Pathology, Amsterdam Neuroscience - Neuroinfection & -inflammation, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, AII - Infectious diseases, NCA - Neuroinflamation, Medical oncology laboratory, Medical oncology, and CCA - Cancer Treatment and quality of life
Subjects: Adult, integrin, Genetic enhancement, Genetic Vectors, endothelial growth factor receptor, MALIGNANT MENINGIOMAS, Coxsackievirus and adenovirus receptor, In Vitro Techniques, Gene delivery, medicine.disease_cause, meningioma, EPIDERMAL GROWTH-FACTOR, Adenoviridae, CELL-PROLIFERATION, THYMIDINE KINASE, Growth factor receptor, Epidermal growth factor, Spheroids, Cellular, RADIATION-THERAPY, Meningeal Neoplasms, Tumor Cells, Cultured, INTRACRANIAL MENINGIOMAS, Humans, Medicine, GLIOMA-CELLS, IN-VIVO, Aged, business.industry, Genetic transfer, Gene Transfer Techniques, Genetic Therapy, adenovirus, Middle Aged, Cell sorting, gene therapy, NONSURGICAL TREATMENT, FACTOR RECEPTOR, Cell culture, Gene Targeting, Cancer research, business
Abstract: Object. Due to their surgical inaccessibility or aggressive behavior, some meningiomas cannot be cured with current treatment strategies. Gene therapy is an emerging strategy for the treatment of brain tumors, which the authors investigated to determine whether adenoviruses could be used for gene transfer in meningioma cells. Methods. The presence of the high-affinity Coxsackievirus and adenovirus receptor (CAR) for adenovirus type 5, as well as endothelial growth factor receptor (EGFR) and alphav integrins (ITGAVs), were analyzed in primary tumors by using immunohistochemical studies and in primary meningioma cell cultures by using fluorescence-activated cell sorting. Targeting of adenoviruses to EGFR was achieved using bispecific antibodies, whereas targeting of adenoviruses to the ITGAVs was accomplished by insertion of an RGD (arginine-glycine-aspartic acid) motif in the adenovirus fiber HI loop. Gene transfer efficiency of untargeted and targeted vectors was compared in primary cell cultures and in spheroids derived from patients' resected tumor material. The presence of CARs was observed in all tumors and in all but one of the derived primary meningioma cells. The higher expression of EGFRs and ITGAVs indicated that these receptors could be used as alternative targets to redirect the adenoviruses. Redirection of adenoviruses to the EGFRs or integrins enhanced gene transfer threefold (range two—sevenfold) for EGFRs in primary meningioma cells and ninefold (range three—23-fold) for integrins (p = 0.002, analysis of variance). The effect of adenovirus targeting was confirmed in spheroids composed of primary meningioma cells. Conclusions. Gene transfer with adenoviruses targeted to tumor-specific receptors is very effective in primary meningioma cells and spheroids. These vectors are promising agents for gene therapy of meningiomas.
Published: 2002

253. Microglia show an intermediate activation status in early lesion formation in multiple sclerosis

Author: Paul van der Valk, Marjolein Breur, Kimberley Ummenthum, Daphne Y.S. Vogel, Priscilla D. A. M. Heijnen, Laura A. N. Peferoen, Wouter H. Gerritsen, Sandra Amor, and Christine D. Dijkstra
Subjects: Pathology, medicine.medical_specialty, medicine.anatomical_structure, Neurology, Microglia, Chemistry, Multiple sclerosis, Immunology, medicine, Immunology and Allergy, Neurology (clinical), Lesion formation, medicine.disease
Published: 2014

254. Demyelination during multiple sclerosis is associated with combined activation of microglia and macrophages by IFN-gamma and alpha B-crystallin

Author: Peter J. Nacken, Inge R. Holtman, Malika Bsibsi, Paul van der Valk, Wouter Gerritsen, Bart J. L. Eggen, Jack van Horssen, Sandra Amor, Maarten Witte, Laura A. N. Peferoen, and Johannes M. van Noort
Subjects: medicine.anatomical_structure, Neurology, Microglia, Chemistry, Multiple sclerosis, Immunology, medicine, Immunology and Allergy, Neurology (clinical), medicine.disease, Molecular biology, Ifn gamma, Alpha B-Crystallin
Published: 2014

255. Endodermal sinus tumor of the maxillary sinus

Author: Paul van der Valk, Gerrit Jan Westerveld, Christian M. Zwaan, Charles R. Leemans, Dorine Bresters, Jasper J. Quak, Otolaryngology / Head & Neck Surgery, Pediatric surgery, Pathology, Amsterdam Neuroscience - Neuroinfection & -inflammation, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, AII - Infectious diseases, and CCA - Cancer Treatment and quality of life
Subjects: Maxillary sinus, business.industry, Maxillary Sinus Neoplasms, Ethmoidectomy, Endodermal Sinus Tumor, Anatomy, Endodermal sinus tumor, medicine.disease, Magnetic Resonance Imaging, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Fatal Outcome, Otorhinolaryngology, 030220 oncology & carcinogenesis, Child, Preschool, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Surgery, Female, 030223 otorhinolaryngology, business
Published: 2001

256. Clonally related but phenotypically divergent human cancer cell lines derived from a single follicular thyroid cancer recurrence (TT2609)

Author: Inge L. Schadee-Eestermans, Paul van der Valk, Johan C. van Mourik, Fré Arwert, Mario A J A Hermsen, Evert H. van der Poest Clement, Albert A. Geldof, Richard T. Versteegh, Paul Lips, Guus A.M.S. van Dongen, Gerrit J.J. Teule, Martin A. Rooimans, Urology, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, Internal medicine, Radiology and nuclear medicine, Human genetics, Amsterdam Neuroscience - Brain Imaging, AII - Inflammatory diseases, Pathology, Amsterdam Neuroscience - Neuroinfection & -inflammation, AII - Infectious diseases, and NCA - Neuroinflamation
Subjects: Male, endocrine system, Pathology, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Transplantation, Heterologous, Mice, Nude, Biology, Thyroglobulin, Mice, Endocrinology, Tumor Cells, Cultured, medicine, Animals, Humans, Thyroid Neoplasms, Follicular thyroid cancer, Tumor Stem Cell Assay, Ploidies, medicine.disease, Microscopy, Electron, Phenotype, Cell culture, Male patient, Karyotyping, Keratins, Female, Neoplasm Recurrence, Local, Tumor Suppressor Protein p53, Cancer cell lines, Cell Division, Neoplasm Transplantation, Human cancer, Iodine
Abstract: Starting from different regional samples taken from a heterogeneous follicular thyroid cancer recurrence in a male patient, a series of cell cultures was initiated. Three stable cancer cell lines were successfully established (TT2609-A02, TT2609-B02 and TT2609-C02) and kept in continuous culture for more than 3 years. The lines are each characterized by a unique set of biological parameters such as morphology, ploidy state, cell proliferation rate, ultrastructure, thyroid marker expression, p53 expression, karyogram, agar clonogenic capacity and tu- morigenicity as xenografts in nude mice. These characterization studies point to a marked heterogeneity at the level of the clinical tumor recurrence. Karyotype analysis of the cell lines showed a pattern of aberrations indicating that the lines are clonally related and that the A02 and C02 lines are subsequently derived from the more "original" tumor cell type B02 after a tetraploidization event. It is concluded that the obtained cell lines represent an in vitro/in vivo model for human follicular thyroid cancer. The availability of a series of cell lines for human follicular thyroid cancer, mimicking the biological heterogeneity observed in patient tumors, enables both detailed fundamental investigation of thyroid cancer cell biology and the experimental exploration of new treatment approaches.
Published: 2001

257. Survival of human glioma cells treated with various combination of temozolomide and X-rays

Author: Paul van der Valk, Jan J. Heimans, Jaap van den Berg, Ben J. Slotman, and Johannes van Rijn
Subjects: Cancer Research, Programmed cell death, Cell Survival, medicine.medical_treatment, Glioma, medicine, Temozolomide, Tumor Cells, Cultured, Humans, Radiology, Nuclear Medicine and imaging, Cytotoxicity, Clonogenic assay, Antineoplastic Agents, Alkylating, Tumor Stem Cell Assay, Radiation, business.industry, Brain Neoplasms, medicine.disease, Combined Modality Therapy, Radiation therapy, Dacarbazine, Cell killing, Oncology, Cell culture, Immunology, Cancer research, business, medicine.drug
Abstract: Purpose: To investigate the effect of temozolomide, a 3-methyl derivative of mitozolomide in combination with X-rays in human glioma-derived cell lines. Methods and Materials: Glioma cell lines D384 and U251 were treated with temozolomide for various periods of time in combinations with X-rays. Temozolomide administration was repeated every 24 h for exposures up to 96 h. Cytotoxicity was determined with a clonogenic assay. Results: Incubation of D384 cells with temozolomide during 24 h prior to or following irradiation results in a moderate enhancement of the cytotoxicity. Prolonged treatment with temozolomide, i.e., 48–96 h before X-rays, causes a stronger potentiation. In contrast, no enhancement is observed in irradiated U251 cells in combination with 24–96 h temozolomide treatment. In addition to single-dose irradiation, we investigated the effect of temozolomide in D384 cells with concomitant fractionated irradiation. A 96-h exposure to temozolomide with simultaneous doses of 2 Gy X-rays at 24-h intervals, causes a significant further reduction in cell survival as compared to fractionated irradiation only. Conclusion: Depending on the cell line, treatment of glioma cells with temozolomide and X-rays can have either an additional effect or potentiate cell killing.
Published: 2000

258. Multidrug Resistance Related Proteins in Primary Cutaneous Lymphomas

Author: George L. Scheffer, M. J. Flens, Willem A. van Vloten, Rik J. Scheper, Johan Toonstra, Christian W. van Haselen, and Paul van der Valk
Subjects: Chemotherapy, Mycosis fungoides, CD30, business.industry, medicine.medical_treatment, T cell, CBCL, Drug resistance, medicine.disease, Lymphoma, medicine.anatomical_structure, immune system diseases, hemic and lymphatic diseases, medicine, Cancer research, business, Multidrug Resistance-Associated Proteins
Abstract: In patients with primary cutaneous B-cell lymphomas (CBCL) and primary cutaneous T-cell lymphomas (CTCL), extracutaneous sites may become involved and then polychemotherapy is indicated. Multi-agent chemotherapy may induce long lasting complete remissions in CBCL’s. Most CTCL’s, especially mycosis fungoides (MF), and CD30 negative primary cutaneous large T-cell lymphoma (PCLTCL) respond poorly or partially to Multi-agent Chemotherapy.
Published: 1999

259. Tracheobronchomalacia due to amyloidosis in a patient with rheumatoid arthritis

Author: Paul van der Valk, Franktien Turkstra, Alexandre E. Voskuyl, Hagen Biermann, Rico N. P. M. Rinkel, Rheumatology, Otolaryngology / Head & Neck Surgery, Intensive care medicine, Pathology, and CCA - Disease profiling
Subjects: medicine.medical_specialty, Fatal outcome, Biopsy, Case Report, Bronchi, Kidney, Arthritis, Rheumatoid, Fatal Outcome, Rheumatology, Tongue, Internal medicine, Abdominal fat, Humans, Medicine, Rheumatoid arthritis, Aged, Tracheobronchomalacia, medicine.diagnostic_test, business.industry, Amyloidosis, General Medicine, medicine.disease, Dermatology, Surgery, Trachea, medicine.anatomical_structure, Female, business
Abstract: In this case report, we describe a patient with longstanding rheumatoid arthritis who developed tracheobronchomalacia with fatal outcome. Despite negative antemortem biopsies of abdominal fat and tongue, amyloid was found postmortem in the trachea and appeared to be associated with tracheobronchomalacia.
Published: 2008

260. Reply to De Maria

Author: Evelyn M. Monninkhof, Cees L. A. van Herwaarden, Job van der Palen, Paul van der Valk, Gerhard A. Zielhuis, and Ron Hendrix
Subjects: Microbiology (medical), Infectious Diseases, business.industry, Medicine, business, Humanities
Published: 2005

261. Characterization of immune response to neurofilament light in experimental autoimmune encephalomyelitis

Author: Regina Peferoen-Baert, Markus Kipp, David Baker, Marion Victor, Fabiola Puentes, Gareth Pryce, Baukje J. van der Star, Sandra Amor, Paul van der Valk, Kimberley Ummenthum, Arie Reijerkerk, Wouter H. Gerritsen, Cordian Beyer, Ruth Huizinga, Pathology, Molecular cell biology and Immunology, and NCA - Neuroinflamation
Subjects: Male, Neurofilament light, Encephalomyelitis, Autoimmune, Experimental, Encephalomyelitis, T-Lymphocytes, Immunology, Axonal damage, Epitopes, T-Lymphocyte, Enzyme-Linked Immunosorbent Assay, Autoantigens, Epitope, Myelin oligodendrocyte glycoprotein, Multiple sclerosis, Cellular and Molecular Neuroscience, Myelin, Mice, Immune system, Antigen, Neurofilament Proteins, medicine, Animals, Neurodegeneration, Experimental autoimmune encephalomyelitis, Microscopy, Confocal, biology, Reverse Transcriptase Polymerase Chain Reaction, General Neuroscience, Research, medicine.disease, Immunohistochemistry, Granzyme B, medicine.anatomical_structure, Neurology, Spinal Cord, biology.protein, Female
Abstract: Journal of neuroinflammation 10, 18 (2013). doi:10.1186/1742-2094-10-118, Published by BioMed Central, London
Published: 2013

262. Differential expression of DNA topoisomerases in non-small cell lung cancer and normal lung

Author: Jan M. M. Walboomers, Giuseppe Giaccone, Paul van der Valk, Giorgio V. Scagliotti, Jannette van Ark-Otte, Rafael Lopez, Otilia Dalesio, Herbert M. Pinedo, Giovanni Capranico, Franco Zunino, and G. Rubio
Subjects: Male, Lung Neoplasms, medicine.medical_treatment, Cell, Type I, Biochemistry, Structural Biology, Carcinoma, Non-Small-Cell Lung, Gene expression, Non-Small-Cell Lung, Southern, Lung, biology, Blotting, Nuclear Proteins, Middle Aged, Prognosis, Immunohistochemistry, Neoplasm Proteins, DNA-Binding Proteins, Isoenzymes, Blotting, Southern, medicine.anatomical_structure, DNA Topoisomerases, Type I, Aged, Antigens, Neoplasm, Female, Humans, Ki-67 Antigen, Ribonucleases, DNA Topoisomerases, Type II, Topoisomerase inhibitor, medicine.drug_class, Biophysics, Type II, Genetics, medicine, Antigens, Lung cancer, Chemotherapy, Cell growth, Topoisomerase, Carcinoma, medicine.disease, Molecular biology, Cell culture, biology.protein, Neoplasm, DNA Topoisomerases
Abstract: DNA topoisomerases are ubiquitous nuclear enzymes, and important targets of cancer chemotherapy. Expression of topoisomerase genes is often correlated with in vitro chemosensitivity. We investigated the expression of the topoisomerase genes in normal lung and non-small cell lung cancer. Expression of topoisomerase II-alpha, topoisomerase II-beta, and topoisomerase I genes has been assessed in tumor samples of 60 patients who underwent operation for a non-small cell lung carcinoma, by RNase protection assay, and by immunohistochemistry. The expression of topoisomerase II-alpha gene was either undetectable or very low in normal lung, while most NSCLC expressed readily quantifiable levels of this gene. No alteration of the topoisomerase II-alpha gene was found by Southern blotting in the NSCLC samples. In contrast to topoisomerase II-alpha, topoisomerase II-beta was expressed in most normal as well as in tumor tissue samples, at a similar level. The levels of expression of both topoisomerase II isoforms was lower than that of human lung cancer cell lines. The results of the topoisomerase II mRNA expression were confirmed by immunohistochemistry. Whereas topoisomerase II-alpha staining was mainly limited to the nucleus, staining with topoisomerase II-beta antibody was exclusively observed in nucleoli. Topoisomerase I was localized in the nuclei and expression was mainly limited to tumor cells. By RNase protection, topoisomerase I expression in NSCLC samples was in the range of that of human lung cancer cell lines. The expression of the topoisomerase genes did not seem to be coordinated. In tumor cells, there was a positive association between expression of topoisomerase II-alpha and Ki-67, a marker of cell proliferation, as assessed by immunohistochemistry, but not with topoisomerase II-beta or topoisomerase I. Clinical characteristics of the patients, and their survival did not appear to be correlated to the level of expression of any of the topoisomerase genes, although a trend towards a shorter survival was observed in patients whose tumors expressed relatively high topoisomerase II-alpha mRNA levels.(1) the two isoforms of topoisomerase II are differentially expressed in normal lung and NSCLC cells; (2) higher topoisomerase II-alpha expression is associated with higher cell proliferation in NSCLC; (3) the expression of topoisomerase II-alpha and topoisomerase I, but not of topoisomerase II-beta, was higher in tumor cells compared to normal lung. Given the differential expression of topoisomerases in normal lung and tumors, research of more potent and specific topoisomerase inhibitors might prove beneficial in non-small cell lung cancer. Immunohistochemistry may be indicated in prospectively investigating the correlation between expression of topoisomerases and results of chemotherapy treatment.
Published: 1995

263. Differential expression of the c-kit proto-oncogene in germ cell tumours

Author: Rik J. Scheper, Miguel A. Izquierdo, Jose R. Germa-Lluch, Paul van der Valk, Ryuzo Ueda, G. Rubio, Takashi Takahashi, Jannette van Ark-Otte, and Giuseppe Giaccone
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Extragonadal, endocrine system diseases, Adolescent, Gene Expression, Stem cell factor, Testicle, Biology, urologic and male genital diseases, medicine.disease_cause, Proto-Oncogene Mas, Pathology and Forensic Medicine, Immunoenzyme Techniques, Testicular Neoplasms, Testis, medicine, Biomarkers, Tumor, Humans, Child, Aged, Intratubular germ cell neoplasia, Infant, Seminoma, Middle Aged, Neoplasms, Germ Cell and Embryonal, medicine.disease, Neoplasm Proteins, Haematopoiesis, Proto-Oncogene Proteins c-kit, medicine.anatomical_structure, Child, Preschool, Female, Carcinogenesis, Germ cell
Abstract: The c-kit proto-oncogene product and its ligand stem cell factor play an important role in haematopoiesis, spermatogenesis, and melanogenesis. Using an anti-c-kit antiserum raised against a synthetic peptide, we studied the immunohistochemical expression of the c-kit gene product in 60 germ cell tumours (GCTs) (53 testicular, 7 extragonadal), derived from primary GCTs in 45 cases and metastatic tumours in 15 cases. Twenty-eight out of 28 seminomas showed c-kit membranous staining in the majority of cells. A similar pattern of expression was seen in intratubular germ cell neoplasia. Nine out of 29 (32 per cent) non-seminomas displayed cytoplasmic, but not membranous, c-kit immunoreactivity in occasional cells. In three mixed GCTs, c-kit expression was limited to the seminoma component. In normal testis, c-kit expression was observed in some basal tubular cells, corresponding to undifferentiated spermatogonia. These results suggest a role for c-kit in the oncogenesis of GCT, where down-regulation of c-kit might be a critical step during progression from seminomas to non-seminomas. Immunohistochemical analysis of c-kit should be considered as a diagnostic aid for GCT and in particular may be helpful in the identification of certain extragonadal seminomas.
Published: 1995

264. P 116 Choroidal and scleral invasion in retinoblastoma A classification proposal

Author: Paul van der Valk, Saskia M. Imhof, K.E.W.P. Tan, A. Y. N. Schouten-van Meeteren, and A.C. van der Moll
Subjects: medicine.medical_specialty, Ophthalmology, Retinoblastoma, business.industry, medicine, medicine.disease, business, Sensory Systems
Published: 1995
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265. Relationship Between Expression of Cellular Genes and Epstein-Barr Virus in Hodgkin’s Disease

Author: Chris J.L.M. Meijer, Paul van der Valk, M. Jiwa, Joost J. Oudejans, Adriaan J. C. van den Brule, and Jau Mm. Walboomers
Subjects: Hodgkin s, medicine.anatomical_structure, Lymphocyte, medicine, Biology, medicine.disease_cause, Virology, Molecular biology, Epstein–Barr virus, Gene
Abstract: The diagnosis of Hodgkin’s disease (HD) is based on the presence of typical Reed-Sternberg (RS) cells in an appropriate cellular environment of “reactive” cells. The origin of the neoplastic cells in HD is still controversial (Hsu et al., 1985; Cabanillas et al., 1988; Hsu et al., 1992; Drexler, 1992). Recent data favour the hypothesis that the RS cells and their mononuclear variants (collectively called H-RS cells) originate from lymphoid cells, although conflicting data have been published about the exact lineage (Cibull et al., 1989; Schmid et al., 1991; Drexler, 1992; Herbst et al., 1993; Koduru et al., 1993). Expression of B or T-cell specific markers on H-RS cells has been described (Oka et al., 1988; Bjarni et al., 1989; Cibull et al., 1989; Schmid et al., 1991). The number of H-RS cells expressing lymphoid differentiation markers may vary considerably among the different histological types. In HD, nodular lymphocyte predominant type the neoplastic cells express B-cell markers (Coles et al., 1988; Kadin et al., 1988), whereas in other subtypes B and/or T-cell markers can be found on H-RS cells in a variable proportion of cases (Oka et al., 1988; Kadin et al., 1988; Bjarni et al., 1989; Cibull et al., 1989).
Published: 1995

266. Comparison of the Preference, Satisfaction, and Critical Errors Made With Genuair ® and HandiHaler ® in patients with COPD

Author: Paul van der Valk, Thomas Ginko, Axel Kroker, Job van der Palen, Esther Garcia Gil, Laura Padullés, B. Seoane, Ludmyla Rekeda, and Martijn Goosens
Subjects: Pulmonary and Respiratory Medicine, Preference satisfaction, COPD, medicine.medical_specialty, business.industry, medicine, Physical therapy, In patient, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine, medicine.disease, business
Published: 2012

267. Expression of Epstein-Barr virus latent gene products and related cellular activation and adhesion molecules in Hodgkin's disease and non-Hodgkin's lymphomas arising in patients without overt pre-existing immunodeficiency

Author: A. Horstman, Chris J.L.M. Meijer, M. Jiwa, Panagiotis Kanavaros, Jan M. M. Walboomers, and Paul van der Valk
Subjects: Pathology, medicine.medical_specialty, Herpesvirus 4, Human, CD30, Lymphocyte, Ki-1 Antigen, medicine.disease_cause, Polymerase Chain Reaction, Herpesviridae, Virus, Pathology and Forensic Medicine, Viral Matrix Proteins, immune system diseases, Antigens, CD, Antigens, Neoplasm, hemic and lymphatic diseases, medicine, Gammaherpesvirinae, Humans, Reed-Sternberg Cells, Antigens, Viral, In Situ Hybridization, biology, CD11 Antigens, Receptors, IgE, Lymphoma, Non-Hodgkin, CD23, Oncogene Proteins, Viral, medicine.disease, biology.organism_classification, Intercellular Adhesion Molecule-1, Epstein–Barr virus, Hodgkin Disease, Lymphocyte Function-Associated Antigen-1, Lymphoma, DNA-Binding Proteins, medicine.anatomical_structure, Epstein-Barr Virus Nuclear Antigens, Cancer research, Cell Adhesion Molecules
Abstract: Epstein-Barr virus (EBV) recently has been associated with Hodgkin's disease (HD) and the EBV genome was found in CD30-positive Reed-Sternberg cells. Therefore, tissue sections from 25 cases of HD, 35 cases of CD30-positive non-Hodgkin's lymphoma (NHL) (seven CD30-positive anaplastic large cell lymphomas [ALCLs] and 28 CD30-positive non-ALCLs), and 12 cases of CD30-negative NHL that previously had been screened for the presence of EBV by polymerase chain reaction and DNA in situ hybridization were studied by immunohistochemistry for the expression of the latent EBV proteins, latent membrane protein (LMP), and Epstein-Barr nuclear antigen-2 (EBNA-2). We also analyzed the expression of the B-cell activation molecule CD23 and the adhesion molecules LFA-1 CD11a and ICAM-1 CD54 because the upregulation of these molecules by LMP and/or EBNA-2 in vitro has been related to the EBV-induced lymphocyte growth. Latent membrane protein expression was found in Reed-Sternberg cells in nine of 25 cases (36%) of HD and in large, occasionally Reed-Sternberg-like tumor cells in six of 47 cases (12%) of NHL; these six tumors were CD30-positive, histologically high-grade NHL (one CD30-positive ALCL and five CD30-positive non-ALCLs). All the LMP-positive cases were also polymerase chain reaction EBV positive while LMP expression was not found in polymerase chain reaction EBV-negative HD and NHL. No staining for EBNA-2 was detected in our series. In view of the transforming potential of the LMP, these findings suggest that EBV may be associated with the development of some cases of HD and CD30-positive NHL. These findings also suggest a correlation between the expression of LMP and the detection of CD30 in tumor cells of HD and NHL. In contrast, no correlation was found between the expression of LMP and the detection of CD23, LFA-1 CD11a , and ICAM-1 CD54 in tumor cells of HD and NHL.
Published: 1993

268. Differential diagnosis of cutaneous large cell lymphomas using monoclonal antibodies reactive in paraffin-embedded skin biopsy specimens

Author: Rein Willemze, R.C. Beljaards, Chris J.L.M. Meijer, Paul van der Valk, and E. Scheffer
Subjects: Pathology, medicine.medical_specialty, Lymphoma, B-Cell, Skin Neoplasms, medicine.drug_class, Dermatology, Monoclonal antibody, Sensitivity and Specificity, Pathology and Forensic Medicine, Diagnosis, Differential, medicine, Biomarkers, Tumor, Humans, Skin, Paraffin Embedding, biology, medicine.diagnostic_test, business.industry, Large cell, Antibodies, Monoclonal, General Medicine, medicine.disease, Immunohistochemistry, Paraffin embedded, Lymphoma, Lymphoma, T-Cell, Cutaneous, Phenotype, Skin biopsy, biology.protein, Lymphoma, Large B-Cell, Diffuse, Antibody, Differential diagnosis, business
Abstract: We studied a large panel of monoclonal antibodies reactive on routinely processed paraffin-embedded tissue to determine their sensitivity and specificity in the diagnosis of 35 primary cutaneous large cell lymphomas of B- (n = 14) and T-cell origin (n = 21). The findings show that differentiation between clinically relevant subgroups can be obtained by a small panel of antibodies including L26, MB2, LN1, MT1, UCHL1, and Ber-H2. Pitfalls in the use of the reagents are discussed.
Published: 1991

269. Phenotypic and genotypic analysis of large-cell lymphomas, formerly classified as true histiocytic lymphoma: identification of an unusual group of tumors

Author: C. J. M. Melief, Herbert V. Stel, Chris J.L.M. Meijer, Paul van der Valk, Theo H. van der Kwast, and Johan W. van Oostveen
Subjects: CD4-Positive T-Lymphocytes, Cancer Research, Pathology, medicine.medical_specialty, Genotype, Receptors, Antigen, T-Cell, Ki-1 Antigen, Histiocytic sarcoma, Biology, Immunoglobulin light chain, True Histiocytic Lymphoma, Antigens, Neoplasm, medicine, Humans, Histiocyte, Gene Rearrangement, Genes, Immunoglobulin, Large cell, Lymphoma, Non-Hodgkin, Hematology, Gene rearrangement, medicine.disease, Antigens, Differentiation, Immunohistochemistry, Non-Hodgkin's lymphoma, Phenotype, Oncology, Monoclonal, Lymphoma, Large B-Cell, Diffuse
Abstract: A group of 12 large-cell lymphomas, seen in the period January 1983 to January 1985 and then tentatively classified as histiocytic sarcomas/true histiocytic lymphomas (i.e. non B-, non T-cell lymphomas, with expression of some histiocytic markers) were restudied phenotypically with a much more extensive range of monoclonal and polyclonal antibodies. They were also genotypically analyzed with respect to rearrangements of genes coding for the immunoglobulin (Ig) heavy and light chains and the gamma and beta chains of the T-cell receptor (TCR). The combined results suggest that these "histiocytic sarcomas" represent a heterogeneous group of large cell lymphomas often with unexpected rearrangements (or lack of rearrangements) of either Ig and TCR genes and phenotypically with coexpression of "histiocytic" and B- or T-cell markers. Such coexpression may be regarded as a warning signal to expect unusual genotype. True histiocytic tumours apparently do exist, but are rare (one case in this study), and their diagnosis is very difficult.
Published: 1990

270. Stage is a better prognostic indicator than morphologic subtype in primary noncutaneous T-cell lymphoma

Author: Thea M. Vroom, L. Arnold Noorduyn, Paul van der Valk, Chris J.L.M. Meijer, Paul Blok, Rein Willemze, and Peter van Heerde
Subjects: Adult, Antigens, Differentiation, T-Lymphocyte, Male, Pathology, medicine.medical_specialty, Cytoplasm, Adolescent, Lymphoma, T-Lymphocytes, Mitosis, Disease, Diagnosis, Differential, Immunoenzyme Techniques, Immunophenotyping, Antigens, CD, Biomarkers, Tumor, Medicine, T-cell lymphoma, Humans, Stage (cooking), Aged, Neoplasm Staging, Cell Nucleus, business.industry, Histocytochemistry, Incidence (epidemiology), Large cell, Cancer, General Medicine, Middle Aged, medicine.disease, Prognosis, Survival Rate, Child, Preschool, Female, business
Abstract: The authors reviewed 28 primary noncutaneous T-cell lymphomas, referred to the Comprehensive Cancer Center Amsterdam, using the updated Kiel classification. Clinical course was related with stage of disease, morphologic subtype, and immunophenotype of the tumor cells. The incidence of primary noncutaneous T-cell lymphomas was 4.1 cases per 1,000,000 people per year. Morphologic classification was difficult and arbitrary, lmmunohistochemistry contributed considerably in diagnosis of this group of tumors. All primary noncutaneous T-cell lymphomas had a poor prognosis, with no significant difference between predominantly small cell (low-grade) and large cell (high-grade) tumors. The only parameter significantly correlating with survival was the stage of the disease at presentation. The results suggest that all types of primary noncutaneous T-cell lymphoma are to be considered high grade and that primary localization (cutaneous vs. noncutaneous) and stage of disease at presentation appear to be more important as predictors of clinical outcome than morphologic or immunophenotypic subtype.
Published: 1990

271. Lack of Correlation Between Cortical Demyelination and White Matter Pathologic Changes in Multiple Sclerosis

Author: Chris H. Polman, Frederik Barkhof, Paul van der Valk, Lars Bø, Jeroen J. G. Geurts, VU University medical center, Radiology and nuclear medicine, Pathology, and Neurology
Subjects: Male, Pathology, medicine.medical_specialty, Multiple Sclerosis, Statistics, Nonparametric, Postmortem Changes, Luxol fast blue stain, Central nervous system disease, White matter, Arts and Humanities (miscellaneous), medicine, Humans, Aged, Aged, 80 and over, Cerebral Cortex, medicine.diagnostic_test, business.industry, Multiple sclerosis, Myelin Basic Protein, Magnetic resonance imaging, Middle Aged, medicine.disease, Immunohistochemistry, Magnetic Resonance Imaging, medicine.anatomical_structure, Cerebral cortex, Female, Histopathology, Autopsy, Neurology (clinical), business, Demyelinating Diseases
Abstract: Background: Histopathologic studies have shown that subpial cortical demyelination is extensive in chronic multiple sclerosis (MS). Objective: To study whether subpial cortical demyelination in MS is associated with focal or diffuse white matter (WM) pathologic features on magnetic resonance imaging (MR imaging). Design: Comparison of postmortem MR imaging findings with histopathologic findings. Setting: Brain donations from a general community. Patients: Three patients with MS with extensive cortical demyelination and 3 patients with minor cortical demyelination were selected from an MS autopsy data set. The postmortem MR imaging and histopathologic data of the patients were compared. Main Outcome Measures: Two observers blinded to the results of each other assessed the presence, extent, and distribution of focal and diffuse pathologic changes in WM by MR imaging and by histopathology. Results: Extensive subpial demyelination was not associated with a significant increase in the area of focal and diffuse WM pathologic changes as assessed by Luxol fast blue histochemistry or by MR imaging or with the presence or extent of juxtacortical abnormalities on MR imaging. Conclusions: The lack of association of MS gray matter demyelination with diffuse or focal WM changes indicates that gray matter demyelination in MS occurs largely independent of WM pathologic changes. The extent or distribution of WM abnormalities cannot be used to identify extensive cortical demyelination in the clinical setting. ©2007 American Medical Association. All rights reserved.
Published: 2007

272. IsChlamydia pneumoniaepresent in the central nervous system of multiple sclerosis patients?

Author: Joep Killestein, Chris J.L.M. Meijer, Paul van der Valk, Servaas A. Morré, Corline J.A. De Groot, Adriaan J. C. van den Brule, and Chris H. Polman
Subjects: Chlamydia, medicine.anatomical_structure, Neurology, business.industry, Multiple sclerosis, Immunology, Central nervous system, medicine, Neurology (clinical), medicine.disease, business
Published: 2000

273. Induction of nitric oxide synthase in multiple sclerosis lesions

Author: Paul van der Valk, J.W. Theeuwes, Christine D. Dijkstra, S.R. Ruuls, and C. de Groot
Subjects: Nitric oxide synthase, biology, Chemistry, Multiple sclerosis, Immunology, medicine, biology.protein, Immunology and Allergy, Pharmacology, medicine.disease
Published: 1997

274. Nitric oxide synthase activity of human adult astrocytes and brain macrophages in multiple sclerosis

Author: Paul van der Valk, C. de Groot, S.R. Ruuls, M. Veldwijk, and K. Weber
Subjects: Nitric oxide synthase, Neurology, biology, Chemistry, Multiple sclerosis, Immunology, medicine, biology.protein, Immunology and Allergy, Neurology (clinical), Pharmacology, medicine.disease
Published: 1995

275. Phagocytic capacity of adult human astrocytes in culture

Author: Corline J.A. De Groot, Paul van der Valk, and R.G.V. Smolders
Subjects: Neurology, Immunology, Immunology and Allergy, Neurology (clinical)
Published: 1994

276. Post-mortem delay effects on rat neuroglial cells and brain macrophages

Author: Corline J.A. De Groot, Christine D. Dijkstra, Paul van der Valk, and J.W. Theeuwes
Subjects: Pathology, medicine.medical_specialty, Neurology, Immunology, medicine, Immunology and Allergy, Neurology (clinical), Biology, Neuroglial cells
Published: 1994

277. Large cell lymphoma. II. Differential diagnosis of centroblastic and B-immunoblastic subtypes by morphometry on cytologic preparations

Author: Penny J. Ball, Paul van der Valk, Piet H. J. Kurver, Jan Lindeman, and Chris J. L. M. Meijer
Subjects: Cancer Research, Oncology
Published: 1985

278. Large cell lymphomas. I. Differential diagnosis of centroblastic and b-immunoblastic subtypes by morphometry on histologic preparations

Author: Piet H. J. Kurver, Paul van der Valk, J. Lindeman, Chris J.L.M. Meijer, and Penny J. Ball
Subjects: Cancer Research, Pathology, medicine.medical_specialty, Nucleolus, business.industry, Large cell, Large-cell lymphoma, medicine.disease, Nuclear shape, Immunoblast, Lymphoma, Oncology, Cytology, medicine, Differential diagnosis, business
Abstract: Thirty-three large cell lymphomas, 18 centroblastic or large noncleaved follicle center cell lymphomas and 15 B-immunoblastic lymphomas, diagnosed by morphology and marker studies, were studied with morphometry. The following parameters were studied: nuclear and nucleolar area, nuclear shape, cytoplasm-to-nucleus ratio, number of nucleoli per nuclear cross section, location of the nucleolus within the nucleus as expressed by the relative nucleolar eccentricity (rNE), and the percentage of morphometrically defined immunoblasts. Mean values and standard deviations (SDs) were calculated and statistically analyzed. The two groups differed significantly in their nucleolar area (mean and SD), cytoplasm-to-nucleus ratio (mean), number of nucleoli per nuclear cross section (mean and SD), rNE (mean), and percentage of immunoblasts. Using nonlinear discriminant analysis, the possibility of classifying individual cases with the studied parameters was investigated. Twenty-nine cases were reliably classified (88%); three were classified correctly, but with less than a 95% certainty, and 1 case was misclassified. The results indicate a spectrum ranging from centroblastic to B-immunoblastic lymphoma. Transition forms occur and can be accurately defined with morphometry.
Published: 1984

279. Small cell carcinoma of the urinary bladder. A clinicopathologic, morphometric, immunohistochemical, and ultrastructural study of 18 cases

Author: Paul van der Valk, C. Edward Blomjos, W. Vos, Chris J.L.M. Meijer, and Herman J. de Voogt
Subjects: Cancer Research, Pathology, medicine.medical_specialty, Urinary bladder, Bladder cancer, business.industry, medicine.medical_treatment, Combination chemotherapy, medicine.disease, Neuroendocrine differentiation, Small-cell carcinoma, Cystectomy, medicine.anatomical_structure, Transitional cell carcinoma, Oncology, medicine, Small Cell Lung Carcinoma, business
Abstract: A multiinstitutional review of 3778 patients with a primary malignancy of the urinary bladder revealed 18 cases (0.48%) of small cell carcinoma which were histologically and morphometrically identical to pulmonary small cell undifferentiated carcinoma. Age, sex, and symptoms at first presentation were comparable to that known in transitional cell carcinoma. Sixteen patients (89%) developed metastatic disease, with most frequent involvement of regional lymph nodes, liver, skeleton, and abdominal cavity. The unfavorable clinical outcome was worse as compared with that reported in advanced stage poorly differentiated transitional cell carcinoma, and was similar to the rapidly fatal outcome of pulmonary small cell undifferentiated carcinoma. Fourteen patients (78%) died by tumor at a mean follow-up period of 9.4 months, and only one patient was free of recurrent disease more than 5 years after cystectomy. This apparent aggressive tumor behavior was independent of the presence of neuroendocrine differentiation characteristics at immunohistochemical (13 cases, 72%) or electron microscopic study (eight cases, 44%). The prolonged survival periods (15--38 months) of the five patients who received combination chemotherapy suggested that, just as in small cell lung carcinoma, chemotherapy may be profitable. A unified concept of histogenesis of bladder cancer with a common origin from a multipotent mucosal stem cell is proposed.
Published: 1989

280. Peripheral T-cell lymphomas: a clinicopathological and immunological study of 10 cases

Author: Paul van der Valk, C. J. L. M. Meijer, and R. Willemze
Subjects: Adult, Male, Poor prognosis, Pathology, medicine.medical_specialty, Cytoplasm, Histology, Adolescent, Lymphoma, T cell, T-Lymphocytes, Classification scheme, Pathology and Forensic Medicine, Immunoenzyme Techniques, Immunophenotyping, hemic and lymphatic diseases, Medicine, T-cell lymphoma, Humans, Aged, Skin, Cell Nucleus, Mycosis fungoides, business.industry, Histocytochemistry, Histocompatibility Antigens Class II, General Medicine, HLA-DR Antigens, Middle Aged, medicine.disease, Peripheral, medicine.anatomical_structure, Antigens, Surface, Immunohistochemistry, Female, Lymph Nodes, business
Abstract: Diagnosis and classification of T-cell lymphomas is notoriously difficult. Existing classification schemes are insufficient. Some clinicopathologically well defined T-cell lymphomas exist (mycosis fungoides, Sezary's syndrome, and T-lymphoblastic lymphomas) but the remaining tumours, frequently called peripheral T-cell lymphomas, are a heterogeneous group, clinically, morphologically and immunologically. The data on 10 peripheral T-cell lymphomas are presented and compared to data from the literature. Patients were elderly, had a high frequency of extranodal localizations (notably the skin 75%) and had a poor prognosis: five of 10 patients have died, median survival 22 months. Morphologically and immunophenotypically the group is very heterogeneous. The variety of blast cell morphology is emphasized. No correlations were found between immunophenotype and prognosis, or immunophenotype and morphology.
Published: 1986

281. Pathologie in tijden van Corona: de rol van ACE2 in SARS en COVID19

Author: Wim Timens, Harry van Goor, Jan von der Thusen, Katrien Grunberg, and Paul van der Valk

282. Can we change the activity behaviour of patients with COPD using a telemedicine feedback intervention?

Author: Monique Tabak, Miriam Vollenbroek-Hutten, Paul van der Valk, Job van der Palen, and Hermie Hermens
Subjects: METIS-279658, COPD, EWI-20525, daily activity, IR-78327, Telemedicine, Feedback
Abstract: Better insight in activity behaviour of COPD patients is needed as a first step to enable more effective tailoring of their treatment. Our objective was (1) to get insight in the daily activity pattern of COPD patients and (2) to investigate whether this can be altered by providing ambulant personalized feedback via a PDA on the activity level during the day. Our preliminary results indicate that our telemedicine feedback intervention is able to increase activity levels and balance activity patterns over the day.

283. Tumors of the infratemporal fossa

Author: Rammohan Tiwari, Jasper J. Quak, Paul van der Valk, Isaäc van der Waal, Rene Leemans, Saskia Egeler, Ludi Smeele, Other departments, and MKA (OUD, ACTA)
Subjects: medicine.medical_specialty, Metastatic lesions, Surgical approach, business.industry, Infratemporal fossa, Signs and symptoms, Original Articles, Surgery, Tumor excision, medicine.anatomical_structure, Paranasal sinuses, medicine, Histopathology, Neurology (clinical), business, Orbit (anatomy)
Abstract: Neoplastic processes involving the infratemporal fossa may originate from the tissues in the region, but more often are the result of extension from neighboring structures. Metastatic lesions located in the region are rarely encountered. Because of its concealed localization, tumors may remain unnoticed for some time. Clincial signs and symptoms often arise late, are insidious, and may be mistakenly attributed to other structures. The close proximity of the area to the intracranial structures, the orbit, the paranasal sinuses, the nasopharynx, and the facial area demands careful planning of surgical excision and combined procedures may be called for. Modern imaging techniques have made three-dimensional visualization of the extent of the pathology possible. Treatment depends on the histopathology and staging of the tumor. Several surgical approaches have been developed over the years. Radical tulor excision with preservation of the quality of life remain the ultimate goal for those tumors where surgery is indicated. Experience over a decade with various pathologies is presented.

284. Expression of IL-1β in rhesus EAE and MS lesions is mainly induced in the CNS itself

Author: Paul van der Valk, Ella A. Zuiderwijk-Sick, Saskia M. Burm, Jeffrey J. Bajramovic, Laura A. N. Peferoen, Jan Bauer, Krista G. Haanstra, Sandra Amor, Bert A. 't Hart, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Pathology
Subjects: Central Nervous System, Male, Pathology, Interleukin-1beta, Inflammasome, Pathogenesis, 0302 clinical medicine, Preactive lesion, Aged, 80 and over, Experimental autoimmune encephalomyelitis, Microglia, General Neuroscience, Microfilament Proteins, Interleukin, Nuclear Proteins, Middle Aged, DNA-Binding Proteins, medicine.anatomical_structure, Neurology, IL-1β, Cytokines, Female, medicine.symptom, Adult, medicine.medical_specialty, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, Central nervous system, Immunology, Lesion, 03 medical and health sciences, Cellular and Molecular Neuroscience, Parenchyma, medicine, Animals, Calgranulin B, Humans, Aged, business.industry, Multiple sclerosis, Research, Calcium-Binding Proteins, medicine.disease, Macaca mulatta, Disease Models, Animal, Trans-Activators, business, 030217 neurology & neurosurgery, 030215 immunology, Transcription Factors
Abstract: Background Interleukin (IL)-1β is a pro-inflammatory cytokine that plays a role in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the animal model for MS. Yet, detailed studies on IL-1β expression in different stages of MS lesion development and a comparison of IL-1β expression in MS and EAE are lacking. Methods Here, we performed an extensive characterization of IL-1β expression in brain tissue of MS patients, which included different MS lesion types, and in brain tissue of rhesus macaques with EAE. Results In rhesus EAE brain tissue, we observed prominent IL-1β staining in MHC class II+ cells within perivascular infiltrates and at the edges of large demyelinating lesions. Surprisingly, staining was localized to resident microglia or differentiated macrophages rather than to infiltrating monocytes, suggesting that IL-1β expression is induced within the central nervous system (CNS). By contrast, IL-1β staining in MS brain tissue was much less pronounced. Staining was found in the parenchyma of active and chronic active MS lesions and in nodules of MHC class II+ microglia in otherwise normal appearing white matter. IL-1β expression was detected in a minority of the nodules only, which could not be distinguished by the expression of pro- and anti-inflammatory markers. These nodules were exclusively found in MS, and it remains to be determined whether IL-1β+ nodules are destined to progress into active lesions or whether they merely reflect a transient response to cellular stress. Conclusions Although the exact localization and relative intensity of IL-1β expression in EAE and MS is different, the staining pattern in both neuroinflammatory disorders is most consistent with the idea that the expression of IL-1β during lesion development is induced in the tissue rather than in the periphery. Electronic supplementary material The online version of this article (doi:10.1186/s12974-016-0605-8) contains supplementary material, which is available to authorized users.
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285. Facilitators and barriers of adherence to exacerbation action plans in patients with COPD and comorbidities: a qualitative study

Author: Jade Schrijver, Tanja Effing, Job van der Palen, Anke Lenferink, Paul van der Valk, Suzanne Hoftijzer, Marjolein Brusse-Keizer, Research Methodology, Measurement and Data Analysis, and Health Technology & Services Research
Subjects: COPD, medicine.medical_specialty, Action (philosophy), Exacerbation, business.industry, Medicine, In patient, business, medicine.disease, Intensive care medicine, Qualitative research

286. Receptor conversion in distant breast cancer metastases

Author: Joost Bart, Paul van der Valk, Laurien D.C. Hoefnagel, Elisabeth G.E. de Vries, Petra van der Groep, Henk Jan Van Slooten, Joost J. Oudejans, Marc J. van de Vijver, Paul J. van Diest, Cornelis A. Seldenrijk, Elsken van der Wall, Pieter J. Westenend, Iris D. Nagtegaal, Pieter Wesseling, Jelle Wesseling, Pathology, Human genetics, CCA - Immuno-pathogenesis, Faculteit der Geneeskunde, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Targeted Gynaecologic Oncology (TARGON), and CCA -Cancer Center Amsterdam
Subjects: Adult, EXPRESSION, Pathology, medicine.medical_specialty, Lung Neoplasms, Skin Neoplasms, Receptor, ErbB-2, IMPACT, Estrogen receptor, Breast Neoplasms, Immunophenotyping, Breast cancer, Surgical oncology, Translational research [ONCOL 3], Progesterone receptor, Biomarkers, Tumor, medicine, Humans, HETEROGENEITY, Neoplasm Metastasis, HER-2 STATUS, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), PROGESTERONE-RECEPTOR, Aged, Gastrointestinal Neoplasms, Aged, 80 and over, Medicine(all), ENDOCRINE THERAPY, Brain Neoplasms, business.industry, Liver Neoplasms, Estrogen Receptor alpha, Middle Aged, IN-SITU HYBRIDIZATION, medicine.disease, Immunohistochemistry, Primary tumor, DISCORDANCE, Gene Expression Regulation, Neoplastic, ESTROGEN-RECEPTOR, Female, OVEREXPRESSION, Receptors, Progesterone, business, Estrogen receptor alpha, Research Article
Abstract: Introduction: When breast cancer patients develop distant metastases, the choice of systemic treatment is usually based on tissue characteristics of the primary tumor as determined by immunohistochemistry (IHC) and/or molecular analysis. Several previous studies have shown that the immunophenotype of distant breast cancer metastases may be different from that of the primary tumor (receptor conversion), leading to inappropriate choice of systemic treatment. The studies published so far are however small and/or methodologically suboptimal. Therefore, definite conclusions that may change clinical practice could not yet be drawn. We therefore aimed to study receptor conversion for estrogen receptor alpha (ER alpha), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in a large group of distant (non-bone) breast cancer metastases by re-staining all primary tumors and metastases with current optimal immunohistochemical and in situ hybridization methods on full sections.Methods: A total of 233 distant breast cancer metastases from different sites (76 skin, 63 liver, 43 lung, 44 brain and 7 gastro-intestinal) were IHC stained for ER alpha, PR and HER2, and expression was compared to that of the primary tumor. HER2 in situ hybridization (ISH) was done in cases of IHC conversion or when primary tumors or metastases showed an IHC 2+ result.Results: Using a 10% threshold, receptor conversion by IHC for ER alpha, PR occurred in 10.3%, 30.0% of patients, respectively. In 10.7% of patients, conversion from ER+ or PR+ to ER-/PR- and in 3.4% from ER-/PR- to ER+ or PR+ was found. Using a 1% threshold, ER alpha and PR conversion rates were 15.1% and 32.6%. In 12.4% of patients conversion from ER+ or PR+ to ER-/PR-, and 8.2% from ER-/PR-to ER+ or PR+ occurred. HER2 conversion occurred in 5.2%. Of the 12 cases that showed HER2 conversion by IHC, 5 showed also conversion by ISH. One further case showed conversion by ISH, but not by IHC. Conversion was mainly from positive in the primary tumor to negative in the metastases for ER alpha and PR, while HER2 conversion occurred equally both ways. PR conversion occurred significantly more often in liver, brain and gastro-intestinal metastases.Conclusions: Receptor conversion by immunohistochemistry in (non-bone) distant breast cancer metastases does occur, is relatively uncommon for ER alpha and HER2, and is more frequent for PR, especially in brain, liver and gastrointestinal metastases.
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287. Simvastatin affects cell motility and actin cytoskeleton distribution of microglia.

Author: Hedwich F. Kuipers, Angelika A.C. Rappert, A. Mieke Mommaas, Elise S. Van Haastert, Paul Van Der Valk, Hendrikus W.G.M. Boddeke, Knut P.H. Biber, and Peter J. Van Den Elsen
Published: 2006
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288. ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

Author: Abbas, Ali, Abdukahil, Sheryl Ann, Abdulkadir, Nurul Najmee, Abe, Ryuzo, Abel, Laurent, Absil, Lara, Jabal, Kamal Abu, Zayyad, Hiba Abu, Acharya, Subhash, Acker, Andrew, Adachi, Shingo, Adam, Elisabeth, Adriano, Enrico, Adrião, Diana, Ageel, Saleh Al, Ahmed, Shakeel, Aiello, Marina, Ainscough, Kate, Airlangga, Eka, Aisa, Tharwat, Hssain, Ali Ait, Tamlihat, Younes Ait, Akimoto, Takako, Akmal, Ernita, Qasim, Eman Al, Al-dabbous, Tala, Al-Fares, Abdulrahman, Alalqam, Razi, Alberti, Angela, Alegesan, Senthilkumar, Alegre, Cynthia, Alessi, Marta, Alex, Beatrice, Alexandre, Kévin, Alfoudri, Huda, Ali, Adam, Ali, Imran, Shah, Naseem Ali, Sheikh, Naseem Ali, Alidjnou, Kazali Enagnon, Aliudin, Jeffrey, Alkhafajee, Qabas, Allavena, Clotilde, Allou, Nathalie, Altaf, Aneela, Alves, João, Alves, João Melo, Alves, Rita, Amaral, Maria, Amira, Nur, Ammerlaan, Heidi, Ampaw, Phoebe, Andini, Roberto, Andrejak, Claire, Angheben, Andrea, Angoulvant, François, Ansart, Séverine, Anthonidass, Sivanesen, Antonelli, Massimo, de Brito, Carlos Alexandre Antunes, Anwar, Kazi Rubayet, Apriyana, Ardiyan, Arabi, Yaseen, Aragao, Irene, Arancibia, Francisco, Araujo, Carolline, Arcadipane, Antonio, Archambault, Patrick, Arenz, Lukas, Arlet, Jean-Benoît, Arnold-Day, Christel, Aroca, Ana, Arora, Lovkesh, Arora, Rakesh, Artaud-Macari, Elise, Aryal, Diptesh, Asaki, Motohiro, Asensio, Angel, Ashley, Elizabeth, Ashraf, Muhammad, Asif, Namra, Asim, Mohammad, Assie, Jean Baptiste, Asyraf, Amirul, Atique, Anika, Attanyake, A. M. Udara Lakshan, Auchabie, Johann, Aumaitre, Hugues, Auvet, Adrien, Axelsen, Eyvind W., Azemar, Laurène, Azoulay, Cecile, Bach, Benjamin, Bachelet, Delphine, Badr, Claudine, Bævre-Jensen, Roar, Baig, Nadia, Baillie, J. Kenneth, Baird, J Kevin, Bak, Erica, Bakakos, Agamemnon, Bakar, Nazreen Abu, Bal, Andriy, Balakrishnan, Mohanaprasanth, Balan, Valeria, Bani-Sadr, Firouzé, Barbalho, Renata, Barbosa, Nicholas Yuri, Barclay, Wendy S., Barnett, Saef Umar, Barnikel, Michaela, Barrasa, Helena, Barrelet, Audrey, Barrigoto, Cleide, Bartoli, Marie, Bartone, Cheryl, Baruch, Joaquín, Bashir, Mustehan, Basmaci, Romain, Basri, Muhammad Fadhli Hassin, Battaglini, Denise, Bauer, Jules, Rincon, Diego Fernando Bautista, Dow, Denisse Bazan, Beane, Abigail, Bedossa, Alexandra, Bee, Ker Hong, Begum, Husna, Behilill, Sylvie, Beiruti, Karine, Beishuizen, Albertus, Beljantsev, Aleksandr, Bellemare, David, Beltrame, Anna, Beltrão, Beatriz Amorim, Beluze, Marine, Benech, Nicolas, Benjiman, Lionel Eric, Benkerrou, Dehbia, Bennett, Suzanne, Bento, Luís, Berdal, Jan-Erik, Bergeaud, Delphine, Bergin, Hazel, Sobrino, José Luis Bernal, Bertoli, Giulia, Bertolino, Lorenzo, Bessis, Simon, Betz, Adam, Bevilcaqua, Sybille, Bezulier, Karine, Bhatt, Amar, Bhavsar, Krishna, Bianchi, Isabella, Bianco, Claudia, Bidin, Farah Nadiah, Singh, Moirangthem Bikram, Bin Humaid, Felwa, Bin Kamarudin, Mohd Nazlin, Bissuel, François, Biston, Patrick, Bitker, Laurent, Bitton, Jonathan, Blanco-Schweizer, Pablo, Blier, Catherine, Bloos, Frank, Blot, Mathieu, Blumberg, Lucille, Boccia, Filomena, Bodenes, Laetitia, Bogaarts, Alice, Bogaert, Debby, Boivin, Anne-Hélène, Bolze, Pierre-Adrien, Bompart, François, Bonelli, Patrizia, Bonfasius, Aurelius, Borges, Diogo, Borie, Raphaël, Bosse, Hans Martin, Botelho-Nevers, Elisabeth, Bouadma, Lila, Bouchaud, Olivier, Bouchez, Sabelline, Bouhmani, Dounia, Bouhour, Damien, Bouiller, Kévin, Bouillet, Laurence, Bouisse, Camile, Bounphiengsy, Thipsavanh, Bountthasavong, Latsaniphone, Boureau, Anne-Sophie, Bourke, John, Bouscambert, Maude, Bousquet, Aurore, Bouziotis, Jason, Boxma, Bianca, Boyer-Besseyre, Marielle, Boylan, Maria, Bozza, Fernando Augusto, Braconnier, Axelle, Braga, Cynthia, Brandenburger, Timo, Monteiro, Filipa Brás, Brazzi, Luca, Breen, Dorothy, Breen, Patrick, Brickell, Kathy, Browne, Alex, Browne, Shaunagh, Brozzi, Nicolas, Brunvoll, Sonja Hjellegjerde, Brusse-Keizer, Marjolein, Buchtele, Nina, Buesaquillo, Christian, Bugaeva, Polina, Buisson, Marielle, Buonsenso, Danilo, Burhan, Erlina, Burrell, Aidan, Bustos, Ingrid G., Butnaru, Denis, Cabie, André, Cabral, Susana, Caceres, Eder, Cadoz, Cyril, Callahan, Mia, Calligy, Kate, Calvache, Jose Andres, Caminiti, Caterina, Camões, João, Campana, Valentine, Campbell, Paul, Campisi, Josie, Canepa, Cecilia, Cantero, Mireia, Caraux-Paz, Pauline, Cárcel, Sheila, Cardellino, Chiara Simona, Cardoso, Filipa, Cardoso, Filipe, Cardoso, Nelson, Cardoso, Sofia, Carelli, Simone, Carlacci, Francesca, Carlier, Nicolas, Carmoi, Thierry, Carney, Gayle, Carqueja, Inês, Carret, Marie-Christine, Carrier, François Martin, Carroll, Ida, Carson, Gail, Carvalho, Leonor, Casanova, Maire-Laure, Cascão, Mariana, Casey, Siobhan, Casimiro, José, Cassandra, Bailey, Castañeda, Silvia, Castanheira, Nidyanara, Castor-Alexandre, Guylaine, Castrillón, Henry, Castro, Ivo, Catarino, Ana, Catherine, François-Xavier, Cattaneo, Paolo, Cavalin, Roberta, Cavalli, Giulio Giovanni, Cavayas, Alexandros, Ceccato, Adrian, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chakveatze, Catherine, Chan, Adrienne, Chand, Meera, Auger, Christelle Chantalat, Chapplain, Jean-Marc, Chas, Julie, Chatterjee, Allegra, Chaudry, Mobin, Iñiguez, Jonathan Samuel Chávez, Chen, Anjellica, Chen, Yih-Sharng, Cheng, Matthew Pellan, Cheret, Antoine, Chetta, Alfredo Antonio, Chiarabini, Thibault, Chica, Julian, Chidambaram, Suresh Kumar, Tho, Leong Chin, Chirouze, Catherine, Chiumello, Davide, Cho, Hwa Jin, Cho, Sung-Min, Cholley, Bernard, Chommanam, Danoy, Chopin, Marie-Charlotte, Chow, Ting Soo, Chow, Yock Ping, Christy, Nathaniel, Chua, Hiu Jian, Chua, Jonathan, Cidade, Jose Pedro, Herreros, José Miguel Cisneros, Citarella, Barbara Wanjiru, Ciullo, Anna, Clarke, Emma, Clarke, Jennifer, Granado, Rolando Claure-Del, Clohisey, Sara, Cobb, Perren J., Codan, Cassidy, Cody, Caitriona, Coelho, Alexandra, Coles, Megan, Colin, Gwenhaël, Collins, Michael, Colombo, Sebastiano Maria, Combs, Pamela, Connor, Marie, Conrad, Anne, Contreras, Sofía, Conway, Elaine, Cooke, Graham S., Copland, Mary, Cordel, Hugues, Corley, Amanda, Cornelis, Sabine, Cornet, Alexander Daniel, Corpuz, Arianne Joy, Cortegiani, Andrea, Corvaisier, Grégory, Costigan, Emma, Couffignal, Camille, Couffin-Cadiergues, Sandrine, Courtois, Roxane, Cousse, Stéphanie, Cregan, Rachel, D’Orleans, Charles Crepy, Croonen, Sabine, Crowl, Gloria, Crump, Jonathan, Cruz, Claudina, Berm, Juan Luis Cruz, Rojo, Jaime Cruz, Csete, Marc, Cucino, Alberto, Cullen, Ailbhe, Cummings, Matthew, Curley, Ger, Curley, Gerard, Curlier, Elodie, Curran, Colleen, Custodio, Paula, D’Amico, Federico, D’Aragon, Frédérick, D’Ortenzio, Eric, da Silva Filipe, Ana, Da Silveira, Charlene, Dabaliz, Al-Awwab, Dagens, Andrew, Dahl, John Arne, Dahly, Darren, Dalton, Heidi, Dalton, Jo, Daly, Seamus, Daneman, Nick, Daniel, Corinne, Dankwa, Emmanuelle A, Dantas, Jorge, de Boer, Mark, de Loughry, Gillian, de Mendoza, Diego, De Montmollin, Etienne, de Oliveira França, Rafael Freitas, Oliveira, Ana Isabel de Pinho, De Rosa, Rosanna, De Rose, Cristina, de Silva, Thushan, de Vries, Peter, Deacon, Jillian, Dean, David, Debard, Alexa, DeBenedictis, Bianca, Debray, Marie-Pierre, DeCastro, Nathalie, Dechert, William, Deconninck, Lauren, Decours, Romain, Defous, Eve, Delacroix, Isabelle, Delaveuve, Eric, Delavigne, Karen, Delfos, Nathalie M., Deligiannis, Ionna, Dell’Amore, Andrea, Delmas, Christelle, Delobel, Pierre, Delsing, Corine, Demonchy, Elisa, Denis, Emmanuelle, Deplanque, Dominique, Depuydt, Pieter, Desai, Mehul, Descamps, Diane, Desvallées, Mathilde, Dewayanti, Santi, Dhanger, Pathik, Diallo, Alpha, Diamantis, Sylvain, Dias, André, Dias, Andrea, Diaz, Juan Jose, Diaz, Priscila, Diaz, Rodrigo, Didier, Kévin, Diehl, Jean-Luc, Dieperink, Wim, Dimet, Jérôme, Dinot, Vincent, Diop, Fara, Diouf, Alphonsine, Dishon, Yael, Djossou, Félix, Docherty, Annemarie B., Doherty, Helen, Dondorp, Arjen M, Dong, Andy, Donnelly, Christl A., Donnelly, Maria, Donohue, Chloe, Donohue, Sean, Donohue, Yoann, Doran, Peter, Dorival, Céline, Douangdala, Phouvieng, Douglas, James Joshua, Douma, Renee, Dournon, Nathalie, Downer, Triona, Downey, Joanne, Downing, Mark, Drake, Tom, Driscoll, Aoife, Dror, Amiel A., Dryden, Murray, Fonseca, Claudio Duarte, Dubee, Vincent, Dubos, François, Dubot-Pérès, Audrey, Ducancelle, Alexandre, Duculan, Toni, Dudman, Susanne, Duggal, Abhijit, Dunand, Paul, Dunning, Jake, Duplaix, Mathilde, Durante-Mangoni, Emanuele, Durham III, Lucian, Dussol, Bertrand, Duthoit, Juliette, Duval, Xavier, Dyrhol-Riise, Anne Margarita, Ean, Sim Choon, Echeverria-Villalobos, Marco, Economopoulos, Giorgio, Edelstein, Michael, Egan, Siobhan, Eggesbø, Linn Margrete, Eira, Carla, El Sanharawi, Mohammed, Elapavaluru, Subbarao, Elharrar, Brigitte, Ellerbroek, Jacobien, Ellingjord-Dale, Merete, Eloy, Philippine, Elshazly, Tarek, Elyazar, Iqbal, Enderle, Isabelle, Endo, Tomoyuki, Eng, Chan Chee, Engelmann, Ilka, Enouf, Vincent, Epaulard, Olivier, Escher, Martina, Esperatti, Mariano, Esperou, Hélène, Esposito-Farese, Marina, Estevão, João, Etienne, Manuel, Ettalhaoui, Nadia, Everding, Anna Greti, Evers, Mirjam, Fabre, Isabelle, Fabre, Marc, Faheem, Amna, Fahy, Arabella, Fairfield, Cameron J., Fakar, Zul, Fareed, Komal, Faria, Pedro, Farooq, Ahmed, Fateena, Hanan, Fatoni, Arie Zainul, Faure, Karine, Favory, Raphaël, Fayed, Mohamed, Feely, Niamh, Feeney, Laura, Fernandes, Jorge, Fernandes, Marília Andreia, Fernandes, Susana, Ferrand, François-Xavier, Devouge, Eglantine Ferrand, Ferrão, Joana, Ferrari, Carlo, Ferraz, Mário, Ferreira, Benigno, Ferreira, Isabel, Ferreira, Sílvia, Ferrer-Roca, Ricard, Ferriere, Nicolas, Ficko, Céline, Figueiredo-Mello, Claudia, Finlayson, William, Fiorda, Juan, Flament, Thomas, Flateau, Clara, Fletcher, Tom, Florio, Letizia Lucia, Flynn, Brigid, Flynn, Deirdre, Fogliazza, Federica, Foley, Claire, Foley, Jean, Fomin, Victor, Fonseca, Tatiana, Fontela, Patricia, Forsyth, Simon, Foster, Denise, Foti, Giuseppe, Fourn, Erwan, Fowler, Robert A., Fraher, Marianne, Franch-Llasat, Diego, Fraser, Christophe, Fraser, John F, Freire, Marcela Vieira, Ribeiro, Ana Freitas, French, Craig, Friedrich, Caren, Fritz, Ricardo, Fry, Stéphanie, Fuentes, Nora, Fukuda, Masahiro, Argin, G, Gaborieau, Valérie, Gaci, Rostane, Gagliardi, Massimo, Gagnard, Jean-Charles, Gagné, Nathalie, Gagneux-Brunon, Amandine, Gaião, Sérgio, Skeie, Linda Gail, Gallagher, Phil, Curto, Elena Gallego, Gamble, Carrol, Gani, Yasmin, Garan, Arthur, Garcia, Rebekha, Barrio, Noelia García, Garcia-Diaz, Julia, Garcia-Gallo, Esteban, Garimella, Navya, Garofalo, Federica, Garot, Denis, Garrait, Valérie, Gauli, Basanta, Gault, Nathalie, Gavin, Aisling, Gavrylov, Anatoliy, Gaymard, Alexandre, Gebauer, Johannes, Geraud, Eva, Morlaes, Louis Gerbaud, Germano, Nuno, Ghisulal, Praveen Kumar, Ghosn, Jade, Giani, Marco, Giaquinto, Carlo, Gibson, Jess, Gigante, Tristan, Gilg, Morgane, Gilroy, Elaine, Giordano, Guillermo, Girvan, Michelle, Gissot, Valérie, Gitaka, Jesse, Giwangkancana, Gezy, Glikman, Daniel, Glybochko, Petr, Gnall, Eric, Goco, Geraldine, Goehringer, François, Goepel, Siri, Goffard, Jean-Christophe, Goh, Jin Yi, Golob, Jonathan, Gomes, Rui, Gomez, Kyle, Gómez-Junyent, Joan, Gominet, Marie, Gonçalves, Bronner P., Gonzalez, Alicia, Gordon, Patricia, Gorelik, Yanay, Gorenne, Isabelle, Goubert, Laure, Goujard, Cécile, Goulenok, Tiphaine, Grable, Margarite, Graf, Jeronimo, Grandin, Edward Wilson, Granier, Pascal, Grasselli, Giacomo, Grazioli, Lorenzo, Green, Christopher A., Greene, Courtney, Greenhalf, William, Greffe, Segolène, Grieco, Domenico Luca, Griffee, Matthew, Griffiths, Fiona, Grigoras, Ioana, Groenendijk, Albert, Lordemann, Anja Grosse, Gruner, Heidi, Gu, Yusing, Guarracino, Fabio, Guedj, Jérémie, Guego, Martin, Guellec, Dewi, Guerguerian, Anne-Marie, Guerreiro, Daniela, Guery, Romain, Guillaumot, Anne, Guilleminault, Laurent, de Castro, Maisa Guimarães, Guimard, Thomas, Haalboom, Marieke, Haber, Daniel, Habraken, Hannah, Hachemi, Ali, Hackmann, Amy, Hadri, Nadir, Haidri, Fakhir, Hakak, Sheeba, Hall, Adam, Hall, Matthew, Halpin, Sophie, Hameed, Jawad, Hamer, Ansley, Hamers, Raph L., Hamidfar, Rebecca, Hammarström, Bato, Hammond, Terese, Han, Lim Yuen, Haniffa, Rashan, Hao, Kok Wei, Hardwick, Hayley, Harrison, Ewen M., Harrison, Janet, Harrison, Samuel Bernard Ekow, Hartman, Alan, Hasan, Mohd Shahnaz, Hashmi, Junaid, Hashmi, Madiha, Hayes, Ailbhe, Hays, Leanne, Heerman, Jan, Heggelund, Lars, Hendry, Ross, Hennessy, Martina, Henriquez-Trujillo, Aquiles, Hentzien, Maxime, Hernandez-Montfort, Jaime, Herr, Daniel, Hershey, Andrew, Hesstvedt, Liv, Hidayah, Astarini, Higgins, Dawn, Higgins, Eibhilin, Hinchion, Rita, Hinton, Samuel, Hiraiwa, Hiroaki, Hirkani, Haider, Hitoto, Hikombo, Ho, Antonia, Ho, Yi Bin, Hoctin, Alexandre, Hoffmann, Isabelle, Hoh, Wei Han, Hoiting, Oscar, Holt, Rebecca, Holter, Jan Cato, Horby, Peter, Horcajada, Juan Pablo, Hoshino, Koji, Hoshino, Kota, Houas, Ikram, Hough, Catherine L., Houltham, Stuart, Hsu, Jimmy Ming-Yang, Hulot, Jean-Sébastien, Huo, Stella, Hussain, Iqbal, Ijaz, Samreen, Illes, Hajnal-Gabriela, Imbert, Patrick, Imran, Mohammad, Sikander, Rana Imran, Imtiaz, Aftab, Inácio, Hugo, Dominguez, Carmen Infante, Ing, Yun Sii, Iosifidis, Elias, Ippolito, Mariachiara, Isgett, Sarah, Isidoro, Tiago, Ismail, Nadiah, Isnard, Margaux, Istre, Mette Stausland, Itai, Junji, Ito, Asami, Ivulich, Daniel, Jaafar, Danielle, Jaafoura, Salma, Jabot, Julien, Jackson, Clare, Jamieson, Nina, Jaquet, Pierre, Jassat, Waasila, Jaud-Fischer, Coline, Jaureguiberry, Stéphane, Javidfar, Jeffrey, Jaworsky, Denise, Jego, Florence, Jelani, Anilawati Mat, Jenum, Synne, Jimbo-Sotomayor, Ruth, Joe, Ong Yiaw, García, Ruth N. Jorge, Jørgensen, Silje Bakken, Joseph, Cédric, Joseph, Mark, Joshi, Swosti, Jourdain, Mercé, Jouvet, Philippe, June, Jennifer, Jung, Anna, Jung, Hanna, Juzar, Dafsah, Kafif, Ouifiya, Kaguelidou, Florentia, Kaisbain, Neerusha, Kaleesvran, Thavamany, Kali, Sabina, Kalicinska, Alina, Kalleberg, Karl Trygve, Kalomoiri, Smaragdi, Kamaluddin, Muhammad Aisar Ayadi, Kamaruddin, Zul Amali Che, Kamarudin, Nadiah, Kamineni, Kavita, Kandamby, Darshana Hewa, Kandel, Chris, Kang, Kong Yeow, Kanwal, Darakhshan, Kanyawati, Dyah, Karpayah, Pratap, Karsies, Todd, Kartsonaki, Christiana, Kasugai, Daisuke, Kataria, Anant, Katz, Kevin, Kaur, Aasmine, Kawasaki, Tatsuya, Kay, Christy, Keane, Hannah, Keating, Seán, Kedia, Pulak, Kelly, Andrea, Kelly, Aoife, Kelly, Claire, Kelly, Niamh, Kelly, Sadie, Kelly, Yvelynne, Kelsey, Maeve, Kennedy, Ryan, Kennon, Kalynn, Keomany, Sommay, Kernan, Maeve, Kerroumi, Younes, Keshav, Sharma, Kestelyn, Evelyne, Khalid, Imrana, Khalid, Osama, Khalil, Antoine, Khan, Coralie, Khan, Irfan, Khan, Quratul Ain, Khanal, Sushil, Khatak, Abid, Khawaja, Amin, Kherajani, Krish, Kho, Michelle E., Khoo, Denisa, Khoo, Ryan, Khoo, Saye, Khoso, Nasir, Kiat, Khor How, Kida, Yuri, Kihuga, Harrison, Kiiza, Peter, Granerud, Beathe Kiland, Kildal, Anders Benjamin, Kim, Jae Burm, Kimmoun, Antoine, Kindgen-Milles, Detlef, King, Alexander, Kitamura, Nobuya, Kjetland, Eyrun Floerecke Kjetland, Klenerman, Paul, Klont, Rob, Bekken, Gry Kloumann, Knight, Stephen R, Kobbe, Robin, Kodippily, Chamira, Vasconcelos, Malte Kohns, Koirala, Sabin, Komatsu, Mamoru, Korten, Volkan, Kosgei, Caroline, Kpangon, Arsène, Krawczyk, Karolina, Krishnan, Sudhir, Krishnan, Vinothini, Kruglova, Oksana, Kumar, Deepali, Kumar, Ganesh, Kumar, Mukesh, Vecham, Pavan Kumar, Kuriakose, Dinesh, Kurtzman, Ethan, Kusumastuti, Neurinda Permata, Kutsogiannis, Demetrios, Kutsyna, Galyna, Kyriakoulis, Konstantinos, L’Her, Erwan, Lachatre, Marie, Lacoste, Marie, Laffey, John G., Lagrange, Marie, Laine, Fabrice, Lairez, Olivier, Lakhey, Sanjay, Lalueza, Antonio, Lambert, Marc, Lamontagne, François, Langelot-Richard, Marie, Langlois, Vincent, Lantang, Eka Yudha, Lanza, Marina, Laouénan, Cédric, Laribi, Samira, Lariviere, Delphine, Lasry, Stéphane, Lath, Sakshi, Latif, Naveed, Launay, Odile, Laureillard, Didier, Lavie-Badie, Yoan, Law, Andrew, Law, Andy, Lawrence, Cassie, Lawrence, Teresa, Le, Minh, Le Bihan, Clément, Le Bris, Cyril, Le Falher, Georges, Le Fevre, Lucie, Le Hingrat, Quentin, Le Maréchal, Marion, Le Mestre, Soizic, Le Moal, Gwenaël, Le Moing, Vincent, Le Nagard, Hervé, Le Turnier, Paul, Leal, Ema, Santos, Marta Leal, Lee, Biing Horng, Lee, Heng Gee, Lee, James, Lee, Su Hwan, Lee, Todd C., Lee, Yi Lin, Leeming, Gary, Lefebvre, Bénédicte, Lefebvre, Laurent, Lefevre, Benjamin, LeGac, Sylvie, Lelievre, Jean-Daniel, Lellouche, François, Lemaignen, Adrien, Lemee, Véronique, Lemeur, Anthony, Lemmink, Gretchen, Lene, Ha Sha, Lennon, Jenny, León, Rafael, Leone, Marc, Leone, Michela, Lepiller, Quentin, Lescure, François-Xavier, Lesens, Olivier, Lesouhaitier, Mathieu, Lester-Grant, Amy, Letizia, Andrew, Levy, Bruno, Levy, Yves, Levy-Marchal, Claire, Lewandowska, Katarzyna, Bassi, Gianluigi Li, Liang, Janet, Liaquat, Ali, Liegeon, Geoffrey, Lim, Kah Chuan, Lim, Wei Shen, Lima, Chantre, Lina, Bruno, Lina, Lim, Lind, Andreas, Lingad, Maja Katherine, Lingas, Guillaume, Lion-Daolio, Sylvie, Lissauer, Samantha, Liu, Keibun, Livrozet, Marine, Lizotte, Patricia, Loforte, Antonio, Lolong, Navy, Loon, Leong Chee, Lopes, Diogo, Lopez-Colon, Dalia, Loschner, Anthony L., Loubet, Paul, Loufti, Bouchra, Louis, Guillame, Lourenco, Silvia, Lovelace-Macon, Lara, Low, Lee Lee, Lowik, Marije, Loy, Jia Shyi, Lucet, Jean Christophe, Bermejo, Carlos Lumbreras, Luna, Carlos M., Lungu, Olguta, Luong, Liem, Luque, Nestor, Luton, Dominique, Lwin, Nilar, Lyons, Ruth, Maasikas, Olavi, Mabiala, Oryane, MacDonald, Sarah, Machado, Moïse, Macheda, Gabriel, Sanchez, Juan Macias, Madhok, Jai, Madiha, Hashmi, de la Calle, Guillermo Maestro, Magara, Jacob, Maglietta, Giuseppe, Mahieu, Rafael, Mahy, Sophie, Maia, Ana Raquel, Maier, Lars S., Maillet, Mylène, Maitre, Thomas, Majori, Maria, Malfertheiner, Maximilian, Malik, Nadia, Mallon, Paddy, Maltez, Fernando, Malvy, Denis, Mammi, Patrizia, Manda, Victoria, Mandei, Jose M., Mandelbrot, Laurent, Manetta, Frank, Mankikian, Julie, Manning, Edmund, Manuel, Aldric, Malaque, Ceila Maria Sant’Ana, Marino, Daniel, Marino, Flávio, Markowicz, Samuel, Eid, Charbel Maroun, Marques, Ana, Marquis, Catherine, Marsh, Brian, Marsh, Laura, Marshal, Megan, Marshall, John, Martelli, Celina Turchi, Martin, Dori-Ann, Martin, Emily, Martin-Blondel, Guillaume, Martin-Loeches, Ignacio, Martin-Quiros, Alejandro, Martinelli, Alessandra, Martinot, Martin, Martins, Ana, Martins, João, Martins, Nuno, Rego, Caroline Martins, Martucci, Gennaro, Martynenko, Olga, Marwali, Eva Miranda, Marzukie, Marsilla, Jimenez, Juan Fernado Masa, Maslove, David, Mason, Phillip, Mason, Sabina, Masood, Sobia, Nor, Basri Mat, Matan, Moshe, Fernandes, Henrique Mateus, Mathew, Meghena, Mathieu, Daniel, Mattei, Mathieu, Matulevics, Romans, Maulin, Laurence, Maxwell, Michael, Maynar, Javier, Mayxay, Mayfong, Mazzoni, Thierry, Mc Evoy, Natalie, Mc Sweeney, Lisa, McArthur, Colin, McCarthy, Aine, McCarthy, Anne, McCloskey, Colin, McConnochie, Rachael, McDermott, Sherry, McDonald, Sarah E., McElroy, Aine, McElwee, Samuel, McEneany, Victoria, McGeer, Allison, McKay, Chris, McKeown, Johnny, McLean, Kenneth A., McNally, Paul, McNicholas, Bairbre, McPartlan, Elaine, Meaney, Edel, Mear-Passard, Cécile, Mechlin, Maggie, Meher, Maqsood, Mehkri, Omar, Mele, Ferruccio, Melo, Luis, Memon, Kashif, Mendes, Joao, Menkiti, Ogechukwu, Menon, Kusum, Mentré, France, Mentzer, Alexander J., Mercier, Emmanuelle, Mercier, Noémie, Merckx, Antoine, Mergeay-Fabre, Mayka, Mergler, Blake, Merson, Laura, Meschi, Tiziana, Mesquita, António, Meta, Roberta, Metwally, Osama, Meybeck, Agnès, Meyer, Dan, Meynert, Alison M., Meysonnier, Vanina, Meziane, Amina, Mezidi, Mehdi, Michelagnoli, Giuliano, Michelanglei, Céline, Michelet, Isabelle, Mihelis, Efstathia, Mihnovit, Vladislav, Miranda-Maldonado, Hugo, Misnan, Nor Arisah, Mohamed, Nik Nur Eliza, Mohamed, Tahira Jamal, Moin, Asma, Molina, David, Molinos, Elena, Molloy, Brenda, Mone, Mary, Monteiro, Agostinho, Montes, Claudia, Montrucchio, Giorgia, Moore, Sarah, Moore, Shona C., Cely, Lina Morales, Moro, Lucia, Tutillo, Diego Rolando Morocho, Morton, Ben, Motherway, Catherine, Motos, Ana, Mouquet, Hugo, Perrot, Clara Mouton, Moyet, Julien, Mudara, Caroline, Mufti, Aisha Kalsoom, Muh, Ng Yong, Muhamad, Dzawani, Mullaert, Jimmy, Müller, Fredrik, Müller, Karl Erik, Munblit, Daniel, Muneeb, Syed, Munir, Nadeem, Munshi, Laveena, Murphy, Aisling, Murphy, Lorna, Murris, Marlène, Murthy, Srinivas, Musaab, Himed, Mutti, Carlotta, Muvindi, Himasha, Muyandy, Gugapriyaa, Myrodia, Dimitra Melia, Mohd-Hanafiah, Farah Nadia, Nagpal, Dave, Narasimhan, Mangala, Narayanan, Nageswaran, Khan, Rashid Nasim, Nazerali-Maitland, Alasdair, Neant, Nadège, Neb, Holger, Necsoi, Coca, Nekliudov, Nikita A., Nelwan, Erni, Neto, Raul, Neumann, Emily, Neves, Bernardo, Ng, Pauline Yeung, Ng, Wing Yiu, Nghi, Anthony, Ngure, Jane, Nguyen, Duc, Choileain, Orna Ni, Leathlobhair, Niamh Ni, Nichol, Alistair, Nitayavardhana, Prompak, Nonas, Stephanie, Noordin, Nurul Amani Mohd, Noret, Marion, Norharizam, Nurul Faten Izzati, Norman, Lisa, Notari, Alessandra, Noursadeghi, Mahdad, Nowicka, Karolina, Nowinski, Adam, Nseir, Saad, Nunez, Jose I., Nurnaningsih, Nurnaningsih, Nusantara, Dwi Utomo, Nyamankolly, Elsa, Nygaard, Anders Benteson, Brien, Fionnuala O., Callaghan, Annmarie O., O’Callaghan, Annmarie, O’Donnell, Max, O’Halloran, Sophie, O’Hearn, Katie, O’Neil, Conar, O’Shea, Linda, O’Sullivan, Miriam, Occhipinti, Giovanna, OConnor, Derbrenn, Ogston, Tawnya, Ogura, Takayuki, Oh, Tak-Hyuk, Ohshimo, Shinichiro, Oldakowska, Agnieszka, Oliveira, João, Oliveira, Larissa, Olliaro, Piero L., Ong, David S. Y., Ong, Jee Yan, Oosthuyzen, Wilna, Opavsky, Anne, Openshaw, Peter, Orakzai, Saijad, Orozco-Chamorro, Claudia Milena, Orquera, Andrés, Ortoleva, Jamel, Osatnik, Javier, Othman, Siti Zubaidah, Otiku, Paul, Ouamara, Nadia, Ouissa, Rachida, Owyang, Clark, Oziol, Eric, Pagadoy, Maïder, Pages, Justine, Palacios, Amanda, Palacios, Mario, Palmarini, Massimo, Panarello, Giovanna, Panda, Prasan Kumar, Paneru, Hem, Pang, Lai Hui, Panigada, Mauro, Pansu, Nathalie, Papadopoulos, Aurélie, Parducci, Paolo, Oña, Edwin Fernando Paredes, Parke, Rachael, Parker, Melissa, Parra, Briseida, Parrini, Vieri, Pasha, Taha, Pasquier, Jérémie, Pastene, Bruno, Patauner, Fabian, Patel, Drashti, Pathmanathan, Mohan Dass, Patrão, Luís, Patricio, Patricia, Patrier, Juliette, Patrizi, Laura, Patterson, Lisa, Pattnaik, Rajyabardhan, Paul, Christelle, Paul, Mical, Paulos, Jorge, Paxton, William A., Payen, Jean-François, Peariasamy, Kalaiarasu, Jiménez, Miguel Pedrera, Peek, Giles J., Peelman, Florent, Peiffer-Smadja, Nathan, Peigne, Vincent, Pejkovska, Mare, Pelosi, Paolo, Peltan, Ithan D., Pereira, Rui, Perez, Daniel, Periel, Luis, Perpoint, Thomas, Pesenti, Antonio, Pestre, Vincent, Petrou, Lenka, Petrov-Sanchez, Ventzislava, Petrovic, Michele, Pettersen, Frank Olav, Peytavin, Gilles, Pharand, Scott, Phonemixay, Ooyanong, Piagnerelli, Michael, Picard, Walter, Picone, Olivier, de Piero, Maria, Pierobon, Carola, Piersma, Djura, Pimentel, Carlos, Pinto, Raquel, Pires, Catarina, Pironneau, Isabelle, Piroth, Lionel, Pisi, Roberta, Pitaloka, Ayodhia, Pius, Riinu, Piva, Simone, Plantier, Laurent, Png, Hon Shen, Poissy, Julien, Pokeerbux, Ryadh, Pokorska-Spiewak, Maria, Poli, Sergio, Pollakis, Georgios, Ponscarme, Diane, Popielska, Jolanta, Porto, Diego Bastos, Post, Andra-Maris, Postma, Douwe F., Povoa, Pedro, Póvoas, Diana, Powis, Jeff, Prapa, Sofia, Praphasiri, Viladeth, Preau, Sébastien, Prebensen, Christian, Preiser, Jean-Charles, Prinssen, Anton, Pritchard, Mark G., Priyadarshani, Gamage Dona Dilanthi, Proença, Lucia, Pudota, Sravya, Puéchal, Oriane, Semedi, Bambang Pujo, Pulicken, Mathew, Puntoni, Matteo, Purcell, Gregory, Quesada, Luisa, Quinones-Cardona, Vilmaris, González, Víctor Quirós, Quist-Paulsen, Else, Quraishi, Mohammed, Rabaa, Maia, Rabaud, Christian, Rabindrarajan, Ebenezer, Rafael, Aldo, Rafiq, Marie, Ragazzo, Gabrielle, Rahardjani, Mutia, Ab Rahman, Ahmad Kashfi Haji, Rahman, Rozanah Abd, Rahutullah, Arsalan, Rainieri, Fernando, Rajahram, Giri Shan, Ramachandran, Pratheema, Ramakrishnan, Nagarajan, Ramanathan, Kollengode, Ramli, Ahmad Afiq, Rammaert, Blandine, Ramos, Grazielle Viana, Rampello, Anais, Rana, Asim, Rangappa, Rajavardhan, Ranjan, Ritika, Ranza, Elena, Rapp, Christophe, Rashan, Aasiyah, Rashan, Thalha, Rasheed, Ghulam, Rasmin, Menaldi, Rätsep, Indrek, Rau, Cornelius, Rausa, Francesco, Ravi, Tharmini, Raza, Ali, Real, Andre, Rebaudet, Stanislas, Redl, Sarah, Reeve, Brenda, Rehman, Attaur, Reid, Liadain, Reikvam, Dag Henrik, Reis, Renato, Rello, Jordi, Remppis, Jonathan, Remy, Martine, Ren, Hongru, Renk, Hanna, Resseguier, Anne-Sophie, Revest, Matthieu, Rewa, Oleksa, Reyes, Luis Felipe, Reyes, Tiago, Ribeiro, Maria Ines, Ricchiuto, Antonia, Richardson, David, Richardson, Denise, Richier, Laurent, Ridzuan, Siti Nurul Atikah Ahmad, Riera, Jordi, Rios, Ana L., Rishu, Asgar, Rispal, Patrick, Risso, Karine, Nuñez, Maria Angelica Rivera, Rizer, Nicholas, Robba, Chiara, Roberto, André, Roberts, Stephanie, Robertson, David L., Robineau, Olivier, Roche-Campo, Ferran, Rodari, Paola, Rodeia, Simão, Abreu, Julia Rodriguez, Roessler, Bernhard, Roger, Claire, Roger, Pierre-Marie, Roilides, Emmanuel, Rojek, Amanda, Romaru, Juliette, Roncon-Albuquerque Jr, Roberto, Roriz, Mélanie, Rosa-Calatrava, Manuel, Rose, Michael, Rosenberger, Dorothea, Roslan, Nurul Hidayah Mohammad, Rossanese, Andrea, Rossetti, Matteo, Rossi, Sandra, Rossignol, Bénédicte, Rossignol, Patrick, Rousset, Stella, Roy, Carine, Roze, Benoît, Rusmawatiningtyas, Desy, Russell, Clark D., Ryan, Maeve, Ryan, Maria, Ryckaert, Mazankowski Heart Institute, Ryckaert, Steffi, Holten, Aleksander Rygh, Saba, Isabela, Sacchelli, Luca, Sadaf, Sairah, Sadat, Musharaf, Sahraei, Valla, Saidani, Nadia, Saint-Gilles, Maximilien, Sakiyalak, Pranya, Salahuddin, Nawal, Salazar, Leonardo, Saleem, Jodat, Saleh, Nazal, Sales, Gabriele, Sallaberry, Stéphane, Gandonniere, Charlotte Salmon, Salvator, Hélène, Sanchez, Olivier, Choez, Xavier Sánchez, de Oliveira, Kizy Sanchez, Sanchez-Miralles, Angel, Sancho-Shimizu, Vanessa, Sandhu, Gyan, Sandhu, Zulfiqar, Sandrine, Pierre-François, Sandulescu, Oana, Santos, Marlene, Sarfo-Mensah, Shirley, Banheiro, Bruno Sarmento, Sarmiento, Iam Claire E., Sarton, Benjamine, Satya, Ankana, Satyapriya, Sree, Satyawati, Rumaisah, Saviciute, Egle, Savvidou, Parthena, Saw, Yen Tsen, Schaffer, Justin, Schermer, Tjard, Scherpereel, Arnaud, Schneider, Marion, Schroll, Stephan, Schwameis, Michael, Schwartz, Gary, Scott, Janet T., Scott-Brown, James, 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Skogen, Vegard, Smith, Sue, Smood, Benjamin, Smyth, Coilin, Smyth, Michelle, Snacken, Morgane, So, Dominic, Soh, Tze Vee, Solberg, Lene Bergendal, Solomon, Joshua, Solomon, Tom, Somers, Emily, Sommet, Agnès, Song, Myung Jin, Song, Rima, Song, Tae, Chia, Jack Song, Sonntagbauer, Michael, Soom, Azlan Mat, Søraas, Arne, Søraas, Camilla Lund, Sotto, Alberto, Soum, Edouard, Sousa, Ana Chora, Sousa, Marta, Uva, Maria Sousa, Souza-Dantas, Vicente, Sperry, Alexandra, Spinuzza, Elisabetta, Darshana, B. P. 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W., Tveita, Anders, Twardowski, Pawel, Uchiyama, Makoto, Udayanga, P G Ishara, Udy, Andrew, Ullrich, Roman, Uribe, Alberto, Usman, Asad, Uyeki, Timothy M., Vajdovics, Cristinava, Val-Flores, Luís, Valentini, Piero, Valle, Ana Luiza, Valran, Amélie, Valzano, Ilaria, Van de Velde, Stijn, van den Berge, Marcel, Van der Feltz, Machteld, van der Palen, Job, van der Valk, Paul, Van Der Vekens, Nicky, Van der Voort, Peter, Van Der Werf, Sylvie, van Dyk, Marlice, van Gulik, Laura, Van Hattem, Jarne, van Netten, Carolien, Van Twillert, Gitte, van Veen, Ilonka, Vanel, Noémie, Vanoverschelde, Henk, Varghese, Pooja, Varrone, Michael, Vasudayan, Shoban Raj, Vauchy, Charline, Veeran, Shaminee, Veislinger, Aurélie, Vencken, Sebastian, Ventura, Sara, Verbon, Annelies, Vickers, James, Vidal, José Ernesto, Vieira, César, Vijayan, Deepak, Villanueva, Joy Ann, Villar, Judit, Villeneuve, Pierre-Marc, Villoldo, Andrea, Van Vinh Chau, Nguyen, Vishwanathan, Gayatri, Visseaux, Benoit, Visser, Hannah, Vitiello, Chiara, Vongsouvath, Manivanh, Vonkeman, Harald, Vuotto, Fanny, Wahab, Noor Hidayu, Wahab, Suhaila Abdul, Wahid, Nadirah Abdul, Wainstein, Marina, Shukeri, Wan Fadzlina Wan Muhd, Wang, Chih-Hsien, Webb, Steve, Wei, Jia, Weil, Katharina, Wen, Tan Pei, Wesselius, Sanne, West, T. Eoin, Wham, Murray, Whelan, Bryan, White, Nicole, Wicky, Paul Henri, Wiedemann, Aurélie, Wijaya, Surya Otto, Wille, Keith, Willems, Suzette, Williams, Virginie, Wils, Evert-Jan, Wong, Calvin, Wong, Teck Fung, Wong, Xin Ci, Wong, Yew Sing, Wright, Natalie, Xian, Gan Ee, Xian, Lim Saio, Xuan, Kuan Pei, Xynogalas, Ioannis, Yacoub, Sophie, Yakop, Siti Rohani Binti Mohd, Yamazaki, Masaki, Yazdanpanah, Yazdan, Hing, Nicholas Yee Liang, Yelnik, Cécile, Yeoh, Chian Hui, Yerkovich, Stephanie, Yiaye, Touxiong, Yokoyama, Toshiki, Yonis, Hodane, Yousif, Obada, Yuliarto, Saptadi, Zaaqoq, Akram, Zabbe, Marion, Zacharowski, Kai, Zahid, Masliza, Zahran, Maram, Zaidan, Nor Zaila Binti, Zambon, Maria, Zambrano, Miguel, Zanella, Alberto, Zawadka, Konrad, Zaynah, Nurul, Zayyad, Hiba, Zoufaly, Alexander, Zucman, David, Fryer, Daniel Vidali, Duque, Sara, Fuentes, Yuli V., Baruch, Joaquin, Beane, Abi, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), University of La Sabana = Universitad de la Sabana, University of Queensland [Brisbane], University of British Columbia (UBC), University of Oxford, The investigators acknowledge: This work is part of the Grand Challenges ICODA pilot initiative, delivered by Health Data Research UK and funded by the Bill & Melinda Gates Foundation and the Minderoo Foundation. The philanthropic support of the donors to the University of Oxford’s COVID-19 Research Response Fund, UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z and 220757/Z/20/Z], the Bill & Melinda Gates Foundation [OPP1209135], the National Institute for Health Research (NIHR, award CO-CIN-01), the Medical Research Council (MRC, grant MC_PC_19059), the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE)(award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013), NIHR Clinical Research Network (infrastructure support), CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and was coordinated out of Sunnybrook Research Institute, the endorsement of the Irish Critical Care- Clinical Trials Group, co-ordinated in Ireland by the Irish Critical Care- Clinical Trials Network at University College Dublin and funded by the Health Research Board of Ireland [CTN-2014-12], Rapid European COVID-19 Emergency Response research (RECOVER) [H2020 project 101003589], European Clinical Research Alliance on Infectious Diseases (ECRAID) [965313], COVID clinical management team, AIIMS, Rishikesh, India, Cambridge NIHR Biomedical Research Centre, the dedication and hard work of the Groote Schuur Hospital Covid ICU Team, the Groote Schuur nursing and University of Cape Town registrar bodies coordinated by the Division of Critical Care at the University of Cape Town, Wellcome Trust fellowship [205228/Z/16/Z], the Liverpool School of Tropical Medicine, the University of Oxford, the dedication and hard work of the Norwegian SARS-CoV-2 study team, the Research Council of Norway grant no 312780, a philanthropic donation from Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner, Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 115523 COMBACTE, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies, in-kind contribution, preparedness work conducted by the Short Period Incidence Study of Severe Acute Respiratory Infection, Stiftungsfonds zur Förderung der Bekämpfung der Tuberkulose und anderer Lungenkrankheiten of the City of Vienna, Project Number: APCOV22BGM, Italian Ministry of Health 'Fondi Ricerca corrente–L1P6' to IRCCS Ospedale Sacro Cuore–Don Calabria, Australian Department of Health grant (3273191), Gender Equity Strategic Fund at University of Queensland, Artificial Intelligence for Pandemics (A14PAN) at University of Queensland, the Australian Research Council Centre of Excellence for Engineered Quantum Systems (EQUS, CE170100009), the Prince Charles Hospital Foundation, Australia, UK Medical Research Council Clinical Research Training Fellowship MR/V001671/1, Instituto de Salud Carlos III, Ministerio de Ciencia, Spain, Brazil, National Council for Scientific and Technological Development Scholarship number 303953/2018-7, Firland Foundation, Shoreline, Washington, USA, the French COVID cohort (NCT04262921) is sponsored by INSERM and is funding by the REACTing (REsearch & ACtion emergING infectious diseases) consortium and by a grant of the French Ministry of Health (PHRC n°20-0424). This work uses Data/Material provided by patients and collected by the NHS as part of their care and support #DataSavesLives. The Data/materials used for this research were obtained from ISARIC4C. ISARIC4C Investigators collated the COVID-19 Clinical Information Network (CO-CIN) data., European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Bill & Melinda Gates Foundation, Minderoo Foundation, Commonwealth Foundation, Wellcome Trust, National Institute for Health Research (UK), Medical Research Council (UK), University of Liverpool, Imperial College London, Canadian Institutes of Health Research, Sunnybrook Research Institute, Health Research Board (Ireland), European Commission, All India Institute of Medical Science, University of Cape Town, Research Council of Norway, Innovative Medicines Initiative, Governo Italiano, University of Queensland, Australian Research Council, Prince Charles Hospital Foundation, Instituto de Salud Carlos III, Institut National de la Santé et de la Recherche Médicale (France), Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Garcia-Gallo, Esteban, Merson, Laura, Kennon, Kalynn, Kelly, Sadie, Citarella, Barbara Wanjiru, Fryer, Daniel Vidali, Shrapnel, Sally, Lee, Jame, Duque, Sara, Fuentes, Yuli V, Balan, Valeria, Smith, Sue, Wei, Jia, Gonçalves, Bronner P, Russell, Clark D, Sigfrid, Louise, Dagens, Andrew, Olliaro, Piero L, Baruch, Joaquin, Kartsonaki, Christiana, Dunning, Jake, Rojek, Amanda, Rashan, Aasiyah, Beane, Abi, Murthy, Sriniva, Reyes, Luis Felipe, ISARIC Clinical Characterization Group: Ali Abbas, Sheryl Ann Abdukahil, Nurul Najmee Abdulkadir, Ryuzo Abe, Laurent Abel, Lara Absil, Kamal Abu Jabal, Hiba Abu Zayyad, Subhash Acharya, Andrew Acker, Shingo Adachi, Elisabeth Adam, Enrico Adriano, Diana Adrião, Saleh Al Ageel, Shakeel Ahmed, Marina Aiello, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Eman Al Qasim, Tala Al-Dabbous, Abdulrahman Al-Fares, Razi Alalqam, Angela Alberti, Senthilkumar Alegesan, Cynthia Alegre, Marta Alessi, Beatrice Alex, Kévin Alexandre, Huda Alfoudri, Adam Ali, Imran Ali, Naseem Ali Shah, Naseem Ali Sheikh, Kazali Enagnon Alidjnou, Jeffrey Aliudin, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Aneela Altaf, João Alves, João Melo Alves, Rita Alves, Maria Amaral, Nur Amira, Heidi Ammerlaan, Phoebe Ampaw, Roberto Andini, Claire Andrejak, Andrea Angheben, François Angoulvant, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Kazi Rubayet Anwar, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Ana Aroca, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Motohiro Asaki, Angel Asensio, Elizabeth Ashley, Muhammad Ashraf, Namra Asif, Mohammad Asim, Jean Baptiste Assie, Amirul Asyraf, Anika Atique, A M Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Eyvind W Axelsen, Laurène Azemar, Cecile Azoulay, Benjamin Bach, Delphine Bachelet, Claudine Badr, Roar Bævre-Jensen, Nadia Baig, J Kenneth Baillie, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Andriy Bal, Mohanaprasanth Balakrishnan, Valeria Balan, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Audrey Barrelet, Cleide Barrigoto, Marie Bartoli, Cheryl Bartone, Joaquín Baruch, Mustehan Bashir, Romain Basmaci, Muhammad Fadhli Hassin Basri, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Abigail Beane, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Karine Beiruti, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Dehbia Benkerrou, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Delphine Bergeaud, Hazel Bergin, José Luis Bernal Sobrino, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Adam Betz, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Isabella Bianchi, Claudia Bianco, Farah Nadiah Bidin, Moirangthem Bikram Singh, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, François Bissuel, Patrick Biston, Laurent Bitker, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Lucille Blumberg, Filomena Boccia, Laetitia Bodenes, Alice Bogaarts, Debby Bogaert, Anne-Hélène Boivin, Pierre-Adrien Bolze, François Bompart, Patrizia Bonelli, Aurelius Bonfasius, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Dounia Bouhmani, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Thipsavanh Bounphiengsy, Latsaniphone Bountthasavong, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Jason Bouziotis, Bianca Boxma, Marielle Boyer-Besseyre, Maria Boylan, Fernando Augusto Bozza, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Dorothy Breen, Patrick 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Sebastiano Maria Colombo, Pamela Combs, Marie Connor, Anne Conrad, Sofía Contreras, Elaine Conway, Graham S Cooke, Mary Copland, Hugues Cordel, Amanda Corley, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Andrea Cortegiani, Grégory Corvaisier, Emma Costigan, Camille Couffignal, Sandrine Couffin-Cadiergues, Roxane Courtois, Stéphanie Cousse, Rachel Cregan, Charles Crepy D'Orleans, Sabine Croonen, Gloria Crowl, Jonathan Crump, Claudina Cruz, Juan Luis Cruz Berm, Jaime Cruz Rojo, Marc Csete, Alberto Cucino, Ailbhe Cullen, Matthew Cummings, Ger Curley, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Federico D'Amico, Frédérick D'Aragon, Eric D'Ortenzio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, Andrew Dagens, John Arne Dahl, Darren Dahly, Heidi Dalton, Jo Dalton, Seamus Daly, Nick Daneman, Corinne Daniel, Emmanuelle A Dankwa, Jorge Dantas, Mark de Boer, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira 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Yuan Tee, João Teixeira, Sofia Tejada, Marie-Capucine Tellier, Sze Kye Teoh, Vanessa Teotonio, François Téoulé, Pleun Terpstra, Olivier Terrier, Nicolas Terzi, Hubert Tessier-Grenier, Adrian Tey, Alif Adlan Mohd Thabit, Anand Thakur, Zhang Duan Tham, Suvintheran Thangavelu, Vincent Thibault, Simon-Djamel Thiberville, Benoît Thill, Jananee Thirumanickam, Shaun Thompson, David Thomson, Emma C Thomson, Surain Raaj Thanga Thurai, Duong Bich Thuy, Ryan S Thwaites, Andrea Ticinesi, Paul Tierney, Vadim Tieroshyn, Peter S Timashev, Jean-François Timsit, Bharath Kumar Tirupakuzhi Vijayaraghavan, Noémie Tissot, Jordan Zhien Yang Toh, Maria Toki, Kristian Tonby, Sia Loong Tonnii, Antoni Torres, Margarida Torres, Rosario Maria Torres Santos-Olmo, Hernando Torres-Zevallos, Michael Towers, Tony Trapani, Théo Treoux, Huynh Trung Trieu, Cécile Tromeur, Ioannis Trontzas, Tiffany Trouillon, Jeanne Truong, Christelle Tual, Sarah Tubiana, Helen Tuite, Jean-Marie Turmel, Lance C W Turtle, Anders Tveita, Pawel Twardowski, Makoto Uchiyama, P G Ishara Udayanga, Andrew Udy, Roman Ullrich, Alberto Uribe, Asad Usman, Timothy M Uyeki, Cristinava Vajdovics, Luís Val-Flores, Piero Valentini, Ana Luiza Valle, Amélie Valran, Ilaria Valzano, Stijn Van de Velde, Marcel van den Berge, Machteld Van der Feltz, Job van der Palen, Paul van der Valk, Nicky Van Der Vekens, Peter Van der Voort, Sylvie Van Der Werf, Marlice van Dyk, Laura van Gulik, Jarne Van Hattem, Carolien van Netten, Gitte Van Twillert, Ilonka van Veen, Noémie Vanel, Henk Vanoverschelde, Pooja Varghese, Michael Varrone, Shoban Raj Vasudayan, Charline Vauchy, Shaminee Veeran, Aurélie Veislinger, Sebastian Vencken, Sara Ventura, Annelies Verbon, James Vickers, José Ernesto Vidal, César Vieira, Deepak Vijayan, Joy Ann Villanueva, Judit Villar, Pierre-Marc Villeneuve, Andrea Villoldo, Nguyen Van Vinh Chau, Gayatri Vishwanathan, Benoit Visseaux, Hannah Visser, Chiara Vitiello, Manivanh Vongsouvath, Harald Vonkeman, Fanny Vuotto, Noor Hidayu Wahab, Suhaila Abdul Wahab, Nadirah Abdul Wahid, Marina Wainstein, Wan Fadzlina Wan Muhd Shukeri, Chih-Hsien Wang, Steve Webb, Jia Wei, Katharina Weil, Tan Pei Wen, Sanne Wesselius, T Eoin West, Murray Wham, Bryan Whelan, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Surya Otto Wijaya, Keith Wille, Suzette Willems, Virginie Williams, Evert-Jan Wils, Calvin Wong, Teck Fung Wong, Xin Ci Wong, Yew Sing Wong, Natalie Wright, Gan Ee Xian, Lim Saio Xian, Kuan Pei Xuan, Ioannis Xynogalas, Sophie Yacoub, Siti Rohani Binti Mohd Yakop, Masaki Yamazaki, Yazdan Yazdanpanah, Nicholas Yee Liang Hing, Cécile Yelnik, Chian Hui Yeoh, Stephanie Yerkovich, Touxiong Yiaye, Toshiki Yokoyama, Hodane Yonis, Obada Yousif, Saptadi Yuliarto, Akram Zaaqoq, Marion Zabbe, Kai Zacharowski, Masliza Zahid, Maram Zahran, Nor Zaila Binti Zaidan, Maria Zambon, Miguel Zambrano, Alberto Zanella, Konrad Zawadka, Nurul Zaynah, Hiba Zayyad, Alexander Zoufaly, David Zucman, Durante-Mangoni, Emanuele, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Microbes in Health and Disease (MHD), Garcia-Gallo E., Merson L., Kennon K., Kelly S., Citarella B. W. , Fryer D. V. , Shrapnel S., Lee J., Duque S., Fuentes Y. V. , et al., and Medical Microbiology & Infectious Diseases
Subjects: Eğitim, Social Sciences and Humanities, Information Security and Reliability, Social Sciences (SOC), Sosyal Bilimler ve Beşeri Bilimler, Epidemiology, EDUCATION & EDUCATIONAL RESEARCH, Temel Bilimler (SCI), BİLGİSAYAR BİLİMİ, BİLGİ SİSTEMLERİ, MATHEMATICS, Sociology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Prospective Studies, COMPUTER SCIENCE, INFORMATION SYSTEMS, STATISTICS & PROBABILITY, Matematik, Bilgisayar Bilimi Uygulamaları, Computer Sciences, Bilgi Güvenliği ve Güvenilirliği, EĞİTİM VE EĞİTİM ARAŞTIRMASI, BİLGİ BİLİMİ VE KÜTÜPHANE BİLİMİ, Bilgi sistemi, Computer Science Applications, Kütüphane ve Bilgi Bilimleri, Hospitalization, Natural Sciences (SCI), Physical Sciences, Engineering and Technology, Sosyal Bilimler (SOC), Bilgisayar Bilimi, Statistics, Probability and Uncertainty, Information Systems, Human, Statistics and Probability, Humans, Pandemics, SARS-CoV-2, COVID-19, SOCIAL SCIENCES, GENERAL, Library and Information Sciences, Education, SDG 3 - Good Health and Well-being, Library Sciences, INFORMATION SCIENCE & LIBRARY SCIENCE, İstatistik ve Olasılık, Sosyal ve Beşeri Bilimler, Bilgisayar Bilimleri, Social Sciences & Humanities, Engineering, Computing & Technology (ENG), Sosyoloji, Pandemic, İSTATİSTİK & OLASILIK, Mühendislik, Bilişim ve Teknoloji (ENG), İstatistik, Olasılık ve Belirsizlik, Sosyal Bilimler Genel, COMPUTER SCIENCE, Prospective Studie, Fizik Bilimleri, Viral infection, Mühendislik ve Teknoloji, Kütüphanecilik
Abstract: The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use., This work is part of the Grand Challenges ICODA pilot initiative, delivered by Health Data Research UK and funded by the Bill & Melinda Gates Foundation and the Minderoo Foundation. The philanthropic support of the donors to the University of Oxford’s COVID-19 Research Response Fund; UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z and 220757/Z/20/Z]; the Bill & Melinda Gates Foundation [OPP1209135]; the National Institute for Health Research (NIHR; award CO-CIN-01); the Medical Research Council (MRC; grant MC_PC_19059); the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE)(award 200907); NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927); Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153); NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013); NIHR Clinical Research Network (infrastructure support); CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and was coordinated out of Sunnybrook Research Institute; the endorsement of the Irish Critical Care- Clinical Trials Group, co-ordinated in Ireland by the Irish Critical Care- Clinical Trials Network at University College Dublin and funded by the Health Research Board of Ireland [CTN-2014-12]; Rapid European COVID-19 Emergency Response research (RECOVER) [H2020 project 101003589]; European Clinical Research Alliance on Infectious Diseases (ECRAID) [965313]; COVID clinical management team, AIIMS, Rishikesh, India; Cambridge NIHR Biomedical Research Centre; the dedication and hard work of the Groote Schuur Hospital Covid ICU Team; the Groote Schuur nursing and University of Cape Town registrar bodies coordinated by the Division of Critical Care at the University of Cape Town; Wellcome Trust fellowship [205228/Z/16/Z]; the Liverpool School of Tropical Medicine; the University of Oxford; the dedication and hard work of the Norwegian SARS-CoV-2 study team; the Research Council of Norway grant no 312780; a philanthropic donation from Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner; Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 115523 COMBACTE, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies, in-kind contribution; preparedness work conducted by the Short Period Incidence Study of Severe Acute Respiratory Infection; Stiftungsfonds zur Förderung der Bekämpfung der Tuberkulose und anderer Lungenkrankheiten of the City of Vienna, Project Number: APCOV22BGM; Italian Ministry of Health “Fondi Ricerca corrente–L1P6” to IRCCS Ospedale Sacro Cuore–Don Calabria; Australian Department of Health grant (3273191); Gender Equity Strategic Fund at University of Queensland; Artificial Intelligence for Pandemics (A14PAN) at University of Queensland; the Australian Research Council Centre of Excellence for Engineered Quantum Systems (EQUS, CE170100009); the Prince Charles Hospital Foundation, Australia; UK Medical Research Council Clinical Research Training Fellowship MR/V001671/1; Instituto de Salud Carlos III, Ministerio de Ciencia, Spain; Brazil, National Council for Scientific and Technological Development Scholarship number 303953/2018-7; Firland Foundation, Shoreline, Washington, USA; the French COVID cohort (NCT04262921) is sponsored by INSERM and is funding by the REACTing (REsearch & ACtion emergING infectious diseases) consortium and by a grant of the French Ministry of Health (PHRC n°20-0424).
Published: 2022

289. [Routine histopathological evaluation after appendectomy not necessary].

Author: van der Valk P
Subjects: Humans, Appendectomy methods
Abstract: The article seeks to supply evidence-based data on the usefulness of routine histopathological evaluation of appendectomy specimens taken for non-oncological purposes. Reasons to perform histology are: (1) old-fashioned attitude that everything worth excising is worthy of histological scrutiny, difficult to maintain in days of cost constraint and ever-improving other techniques to assess such questions; (2) quality assurance of surgical indications; (3) patient safety/security reasons, and (4) lack of other techniques to address diagnostical questions. The authors present a rational evaluation of the pros and cons of histological evaluation, arguing that cost reduction, workload reduction for pathologists and prevention of ineffective follow-up measures will outweigh eventual negative effects. As a pathologist I find the authors present a compelling case. We should try to avoid doing unnecessary work.
Published: 2022

290. [Minimally invasive autopsy: the added value of postmortem radiology].

Author: van der Valk P
Subjects: Autopsy methods, Humans, Netherlands, Radiography methods, Autopsy trends, Radiography trends
Abstract: Today, the postmortem is primarily used to evaluate the quality of the care delivered. It is therefore a cause for concern that over past decades the number of postmortems that have been carried out has been declining. One of the reasons for this is the increased attention being paid to the physical integrity of the deceased by physicians and next of kin. However, a large number of studies show that 10-25% of post-mortems reveal a discrepancy between the clinical findings and the results of the postmortem. Postmortem radiological investigations make a minimally-invasive postmortem possible. In a number of cases, the diagnostic value of postmortem radiological investigation approaches that of the postmortem. Various studies show that postmortem radiological investigation has additional value, however, it also entails higher costs and logistical problems. The question is to what extent the Dutch healthcare system is prepared to go to implement this new development?
Published: 2020

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