Cystatin C is associated with adverse COVID-19 outcomes in diverse populations

COVID-19 has highly variable clinical courses. The search for prognostic host factors for COVID-19 outcome is a priority. We performed logistic regression for ICU admission against a polygenic score (PGS) for Cystatin C (CyC) production in patients with COVID-19. We analyzed the predictive value of longitudinal plasma CyC levels in an independent cohort of patients hospitalized with COVID-19. In four cohorts spanning European and African ancestry populations, we identified a significant association between CyC-production PGS and odds of critical illness (n cases=2,319), with the strongest association captured in the UKB cohort (OR 2.13, 95% CI 1.58-2.87, p=7.12e-7). Plasma proteomics from an independent cohort of hospitalized COVID-19 patients ( n cases = 131) demonstrated that CyC production was associated with COVID-specific mortality (p=0.0007). Our findings suggest that CyC may be useful for stratification of patients and it has functional role in the host response to COVID-19.Peer reviewe

Early Neutrophilia Marked by Aerobic Glycolysis Sustains Host Metabolism and Delays Cancer Cachexia

An elevated neutrophil–lymphocyte ratio negatively predicts the outcome of patients with cancer and is associated with cachexia, the terminal wasting syndrome. Here, using murine model systems of colorectal and pancreatic cancer we show that neutrophilia in the circulation and multiple organs, accompanied by extramedullary hematopoiesis, is an early event during cancer progression. Transcriptomic and metabolic assessment reveals that neutrophils in tumor-bearing animals utilize aerobic glycolysis, similar to cancer cells. Although pharmacological inhibition of aerobic glycolysis slows down tumor growth in C26 tumor-bearing mice, it precipitates cachexia, thereby shortening the overall survival. This negative effect may be explained by our observation that acute depletion of neutrophils in pre-cachectic mice impairs systemic glucose homeostasis secondary to altered hepatic lipid processing. Thus, changes in neutrophil number, distribution, and metabolism play an adaptive role in host metabolic homeostasis during cancer progression. Our findings provide insight into early events during cancer progression to cachexia, with implications for therapy

N-ftaloil-glicin-hidroksamska kiselina kao kelator željeza u serumu štakora

The aim of this study was to investigate the activity of N-phthaloyl-glycine-hydroxamic acid (Phth-Gly-HA) as a new iron chelator in vivo to be used in iron overload diseases. After intraperitoneal application of Phth-Gly-HA to male rats (1 mg kg1 body mass) once a day for seven days, iron serum level decreased by 21%, whereas the iron value dropped by 32% in female rats (1.5 mg kg1 body mass). The results indicate that the tested substance has the ability to bind serum iron by complexation. Besides transferrin iron release, mobilization of ferritin iron is also possibleU cilju pronalaženja novog efikasnog kelatora koji bi mogao poslužiti u liječenju bolesti izazvanih viškom željeza, u ovom je radu ispitano djelovanje N-ftaloil-glicin-hidroksamske kiseline (Phth-Gly-HA) in vivo. Istraživan je utjecaj kelatora na razinu željeza u serumu štakora nakon intraperitonealne primjene vodene otopine Phth-Gly-HA (0,1 mg mL1) jednom dnevno tijekom 7 dana. Kontrolne su životinje primale fiziološku otopinu. Kod mužjaka injektiranje test supstancije (1 mg kg1) uzrokovalo je pad serumskog željeza za 21%. Kod ženki je nakon tretmana (1,5 mg kg1) izmjereno sniženje razine željeza za 35%. Rezultati pokazuju da ispitivana supstanca ima sposobnost kompleksiranja serumskog željeza, pretežno transferinskog, ali da postoji mogućnost mobilizacije željeza i iz feritinskih zaliha

Towards an integrated crowdsourcing definition

Crowdsourcing is a relatively recent concept that encompasses many practices. This diversity leads to the blurring of the limits of crowdsourcing that may be identified virtually with any type of internet-based collaborative activity, such as co-creation or user innovation. Varying definitions of crowdsourcing exist, and therefore some authors present certain specific examples of crowdsourcing as paradigmatic, while others present the same examples as the opposite. In this article, existing definitions of crowdsourcing are analysed to extract common elements and to establish the basic characteristics of any crowdsourcing initiative. Based on these existing definitions, an exhaustive and consistent definition for crowdsourcing is presented and contrasted in 11 cases.Estelles Arolas, E.; González-Ladrón-De-Guevara, F. (2012). Towards an integrated crowdsourcing definition. Journal of Information Science. 32(2):189-200. doi:10.1177/0165551512437638S189200322Vukovic, M., & Bartolini, C. (2010). Towards a Research Agenda for Enterprise Crowdsourcing. Leveraging Applications of Formal Methods, Verification, and Validation, 425-434. doi:10.1007/978-3-642-16558-0_36Brabham, D. C. (2008). Crowdsourcing as a Model for Problem Solving. Convergence: The International Journal of Research into New Media Technologies, 14(1), 75-90. doi:10.1177/1354856507084420Vukovic, M. (2009). Crowdsourcing for Enterprises. 2009 Congress on Services - I. doi:10.1109/services-i.2009.56Doan, A., Ramakrishnan, R., & Halevy, A. Y. (2011). Crowdsourcing systems on the World-Wide Web. Communications of the ACM, 54(4), 86. doi:10.1145/1924421.1924442Brabham, D. C. (2008). Moving the crowd at iStockphoto: The composition of the crowd and motivations for participation in a crowdsourcing application. First Monday, 13(6). doi:10.5210/fm.v13i6.2159Huberman, B. A., Romero, D. M., & Wu, F. (2009). Crowdsourcing, attention and productivity. Journal of Information Science, 35(6), 758-765. doi:10.1177/0165551509346786Andriole, S. J. (2010). Business impact of Web 2.0 technologies. Communications of the ACM, 53(12), 67. doi:10.1145/1859204.1859225Denyer, D., Tranfield, D., & van Aken, J. E. (2008). Developing Design Propositions through Research Synthesis. Organization Studies, 29(3), 393-413. doi:10.1177/0170840607088020Egger, M., Smith, G. D., & Altman, D. G. (Eds.). (2001). Systematic Reviews in Health Care. doi:10.1002/9780470693926Tatarkiewicz, W. (1980). A History of Six Ideas. doi:10.1007/978-94-009-8805-7Cosma, G., & Joy, M. (2008). Towards a Definition of Source-Code Plagiarism. IEEE Transactions on Education, 51(2), 195-200. doi:10.1109/te.2007.906776Brabham, D. C. (2009). Crowdsourcing the Public Participation Process for Planning Projects. Planning Theory, 8(3), 242-262. doi:10.1177/1473095209104824Alonso, O., & Lease, M. (2011). Crowdsourcing 101. Proceedings of the fourth ACM international conference on Web search and data mining - WSDM ’11. doi:10.1145/1935826.1935831Bederson, B. B., & Quinn, A. J. (2011). Web workers unite! addressing challenges of online laborers. Proceedings of the 2011 annual conference extended abstracts on Human factors in computing systems - CHI EA ’11. doi:10.1145/1979742.1979606Grier, D. A. (2011). Not for All Markets. Computer, 44(5), 6-8. doi:10.1109/mc.2011.155Heer, J., & Bostock, M. (2010). Crowdsourcing graphical perception. Proceedings of the 28th international conference on Human factors in computing systems - CHI ’10. doi:10.1145/1753326.1753357Heymann, P., & Garcia-Molina, H. (2011). Turkalytics. Proceedings of the 20th international conference on World wide web - WWW ’11. doi:10.1145/1963405.1963473Kazai, G. (2011). In Search of Quality in Crowdsourcing for Search Engine Evaluation. Advances in Information Retrieval, 165-176. doi:10.1007/978-3-642-20161-5_17La Vecchia, G., & Cisternino, A. (2010). Collaborative Workforce, Business Process Crowdsourcing as an Alternative of BPO. Lecture Notes in Computer Science, 425-430. doi:10.1007/978-3-642-16985-4_40Liu, E., & Porter, T. (2010). Culture and KM in China. VINE, 40(3/4), 326-333. doi:10.1108/03055721011071449Oliveira, F., Ramos, I., & Santos, L. (2010). Definition of a Crowdsourcing Innovation Service for the European SMEs. Lecture Notes in Computer Science, 412-416. doi:10.1007/978-3-642-16985-4_37Porta, M., House, B., Buckley, L., & Blitz, A. (2008). Value 2.0: eight new rules for creating and capturing value from innovative technologies. Strategy & Leadership, 36(4), 10-18. doi:10.1108/10878570810888713Ribiere, V. M., & Tuggle, F. D. (Doug). (2010). Fostering innovation with KM 2.0. VINE, 40(1), 90-101. doi:10.1108/03055721011024955Sloane, P. (2011). The brave new world of open innovation. Strategic Direction, 27(5), 3-4. doi:10.1108/02580541111125725Wexler, M. N. (2011). Reconfiguring the sociology of the crowd: exploring crowdsourcing. International Journal of Sociology and Social Policy, 31(1/2), 6-20. doi:10.1108/01443331111104779Whitla, P. (2009). Crowdsourcing and Its Application in Marketing Activities. Contemporary Management Research, 5(1). doi:10.7903/cmr.1145Yang, J., Adamic, L. A., & Ackerman, M. S. (2008). Crowdsourcing and knowledge sharing. Proceedings of the 9th ACM conference on Electronic commerce - EC ’08. doi:10.1145/1386790.1386829Brabham, D. C. (2010). MOVING THE CROWD AT THREADLESS. Information, Communication & Society, 13(8), 1122-1145. doi:10.1080/13691181003624090Giudice, K. D. (2010). Crowdsourcing credibility: The impact of audience feedback on Web page credibility. Proceedings of the American Society for Information Science and Technology, 47(1), 1-9. doi:10.1002/meet.14504701099Stewart, O., Huerta, J. M., & Sader, M. (2009). Designing crowdsourcing community for the enterprise. Proceedings of the ACM SIGKDD Workshop on Human Computation - HCOMP ’09. doi:10.1145/1600150.1600168Maslow, A. H. (1943). A theory of human motivation. Psychological Review, 50(4), 370-396. doi:10.1037/h0054346Veal, A. J. (Ed.). (2002). Leisure and tourism policy and planning. doi:10.1079/9780851995465.0000Dahlander, L., & Gann, D. M. (2010). How open is innovation? Research Policy, 39(6), 699-709. doi:10.1016/j.respol.2010.01.01

Effects of Thiazide on the Expression of TRPV5, Calbindin-D28K, and Sodium Transporters in Hypercalciuric Rats

TRPV5 is believed to play an important role in the regulation of urinary calcium excretion. We assessed the effects of hydrochlorothiazide (HCTZ) on the expression of TRPV5, calbindin-D28K, and several sodium transporters in hypercalciuric rats. Sprague-Dawley rats were divided into 4 groups; control, HCTZ, high salt, and high salt with HCTZ group in experiment 1; control, HCTZ, high calcium (Ca), and high Ca with HCTZ group in experiment 2. To quantitate the expression of TRPV5, calbindin-D28K, and sodium transporters, western blotting was performed. In both experiments, HCTZ significantly decreased urinary calcium excretion. TRPV5 protein abundance decreased in all hypercalciuric rats, and restored by HCTZ in both high salt with HCTZ and high Ca with HCTZ group. Calbindin-D28K protein abundance increased in the high salt and high salt with HCTZ groups, but did not differ among groups in experiment 2. Protein abundance of NHE3 and NKCC2 decreased in all hypercalciuric rats, and were restored by HCTZ in only high Ca-induced hypercalciuric rats. In summary, protein abundance of TRPV5, NHE3, and NKCC2 decreased in all hypercalciuric rats. The hypocalciuric effect of HCTZ is associated with increased protein abundance of TRPV5 in high salt or calcium diet-induced hypercalciuric rats

Chromosome microarray analysis as first-line test in pregnancies with a priori low risk for detection of submicroscopic chromosomal abnormalities

n this study, we aimed to explore the utility of chromosomal microarray analysis (CMA) in groups of pregnancies with a priori low risk for detection of submicroscopic chromosome abnormalities, usually not considered an indication for testing, in order to assess whether CMA improves the detection rate of prenatal chromosomal aberrations. A total of 3000 prenatal samples were processed in parallel using both whole-genome CMA and conventional karyotyping. The indications for prenatal testing included: advanced maternal age, maternal serum screening test abnormality, abnormal ultrasound findings, known abnormal fetal karyotype, parental anxiety, family history of a genetic condition and cell culture failure. The use of CMA resulted in an increased detection rate regardless of the indication for analysis. This was evident in high risk groups (abnormal ultrasound findings and abnormal fetal karyotype), in which the percentage of detection was 5.8% (7/120), and also in low risk groups, such as advanced maternal age (6/1118, 0.5%), and parental anxiety (11/1674, 0.7%). A total of 24 (0.8%) fetal conditions would have remained undiagnosed if only a standard karyotype had been performed. Importantly, 17 (0.6%) of such findings would have otherwise been overlooked if CMA was offered only to high risk pregnancies.The results of this study suggest that more widespread CMA testing of fetuses would result in a higher detection of clinically relevant chromosome abnormalities, even in low risk pregnancies. Our findings provide substantial evidence for the introduction of CMA as a first-line diagnostic test for all pregnant women undergoing invasive prenatal testing, regardless of risk factors