Author: "M. Melissa" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"M. Melissa"' showing total 624 results

Start Over Author "M. Melissa"

624 results on '"M. Melissa"'

101. Changes in Student Attitudes toward Interprofessional Education after Online and In-Person Introductory Learning Activities

Author: M. Melissa Gross, Chamipa Phanudulkitti, Vinoothna Bavireddy, Olivia S. Anderson, Tazin Daniels, Mark Fitzgerald, Debra Mattison, Karthik Nagappan, Vani Patterson, Laura J. Smith, Peggy Ann Ursuy, and Karen B. Farris
Published: 2022

102. Interplanetary protons versus interacting protons in the 2017 September 10 solar eruptive event

Author: Kocharov, L. (Leon), Pesce-Rollins, M. (Melissa), Laitinen, T. (Timo), Mishev, A. (Alexander), Kühl, P. (Patrick), Klassen, A. (Andreas), Jin, M. (Meng), Omodei, N. (Nicola), Longo, F. (Francesco), Webb, D. F. (David F.), Cane, H. V. (Hilary V.), Heber, B. (Bernd), Vainio, R. (Rami), Usoskin, I. (Ilya), Kocharov, L. (Leon), Pesce-Rollins, M. (Melissa), Laitinen, T. (Timo), Mishev, A. (Alexander), Kühl, P. (Patrick), Klassen, A. (Andreas), Jin, M. (Meng), Omodei, N. (Nicola), Longo, F. (Francesco), Webb, D. F. (David F.), Cane, H. V. (Hilary V.), Heber, B. (Bernd), Vainio, R. (Rami), and Usoskin, I. (Ilya)
Abstract: We analyze the relativistic proton emission from the Sun during the eruptive event on 2017 September 10, which caused a ground-level enhancement (GLE 72) registered by the worldwide network of neutron monitors. Using the neutron monitor data and interplanetary transport modeling both along and across interplanetary magnetic field (IMF) lines, we deduce parameters of the proton injection into the interplanetary medium. The inferred injection profile of the interplanetary protons is compared with the profile of the >100 MeV γ-ray emission observed by the Fermi Large Area Telescope, attributed to pion production from the interaction of >300 MeV protons at the Sun. GLE 72 started with a prompt component that arrived along the IMF lines. This was followed by a more prolonged enhancement caused by protons arriving at the Earth across the IMF lines from the southwest. The interplanetary proton event is modeled using two sources—one source at the root of the Earth-connected IMF line and another source situated near the solar western limb. The maximum phase of the second injection of interplanetary protons coincides with the maximum phase of the prolonged >100 MeV γ-ray emission that originated from a small area at the solar western limb, below the current sheet trailing the associated coronal mass ejection (CME). A possible common source of interacting protons and interplanetary protons is discussed in terms of proton acceleration at the CME bow shock versus coronal (re-)acceleration in the wake of the CME.
Published: 2020

103. Prognostic significance of immune cell populations identified by machine learning in colorectal cancer using routine hematoxylin and eosin–stained sections

Author: Väyrynen, J. P. (Juha P.), Lau, M. C. (Mai Chan), Haruki, K. (Koichiro), Väyrynen, S. A. (Sara A.), Costa, A. D. (Andressa Dias), Borowsky, J. (Jennifer), Zhao, M. (Melissa), Fujiyoshi, K. (Kenji), Arima, K. (Kota), Twombly, T. S. (Tyler S.), Kishikawa, J. (Junko), Gu, S. (Simeng), Aminmozaffari, S. (Saina), Shi, S. (Shanshan), Baba, Y. (Yoshifumi), Akimoto, N. (Naohiko), Ugai, T. (Tomotaka), Da Silva, A. (Annacarolina), Song, M. (Mingyang), Wu, K. (Kana), Chan, A. T. (Andrew T.), Nishihara, R. (Reiko), Fuchs, C. S. (Charles S.), Meyerhardt, J. A. (Jeffrey A.), Giannakis, M. (Marios), Ogino, S. (Shuji), Nowak, J. A. (Jonathan A.), Väyrynen, J. P. (Juha P.), Lau, M. C. (Mai Chan), Haruki, K. (Koichiro), Väyrynen, S. A. (Sara A.), Costa, A. D. (Andressa Dias), Borowsky, J. (Jennifer), Zhao, M. (Melissa), Fujiyoshi, K. (Kenji), Arima, K. (Kota), Twombly, T. S. (Tyler S.), Kishikawa, J. (Junko), Gu, S. (Simeng), Aminmozaffari, S. (Saina), Shi, S. (Shanshan), Baba, Y. (Yoshifumi), Akimoto, N. (Naohiko), Ugai, T. (Tomotaka), Da Silva, A. (Annacarolina), Song, M. (Mingyang), Wu, K. (Kana), Chan, A. T. (Andrew T.), Nishihara, R. (Reiko), Fuchs, C. S. (Charles S.), Meyerhardt, J. A. (Jeffrey A.), Giannakis, M. (Marios), Ogino, S. (Shuji), and Nowak, J. A. (Jonathan A.)
Abstract: Purpose: Although high T-cell density is a well-established favorable prognostic factor in colorectal cancer, the prognostic significance of tumor-associated plasma cells, neutrophils, and eosinophils is less well-defined. Experimental Design: We computationally processed digital images of hematoxylin and eosin (H&E)–stained sections to identify lymphocytes, plasma cells, neutrophils, and eosinophils in tumor intraepithelial and stromal areas of 934 colorectal cancers in two prospective cohort studies. Multivariable Cox proportional hazards regression was used to compute mortality HR according to cell density quartiles. The spatial patterns of immune cell infiltration were studied using the GTumor:Immune cell function, which estimates the likelihood of any tumor cell in a sample having at least one neighboring immune cell of the specified type within a certain radius. Validation studies were performed on an independent cohort of 570 colorectal cancers. Results: Immune cell densities measured by the automated classifier demonstrated high correlation with densities both from manual counts and those obtained from an independently trained automated classifier (Spearman’s ρ 0.71–0.96). High densities of stromal lymphocytes and eosinophils were associated with better cancer-specific survival [Ptrend < 0.001; multivariable HR (4th vs 1st quartile of eosinophils), 0.49; 95% confidence interval, 0.34–0.71]. High GTumor:Lymphocyte area under the curve (AUC0,20μm; Ptrend = 0.002) and high GTumor:Eosinophil AUC0,20μm (Ptrend < 0.001) also showed associations with better cancer-specific survival. High stromal eosinophil density was also associated with better cancer-specific survival in the validation cohort (Ptrend < 0.001). Conclusions: These findings highlight the potential for machine learning assessment of H&E-stained sections to provide robust, quantitative tumor-immune biomarkers for precision medicine.
Published: 2020

104. Recommendations for Systemic Antimicrobial Therapy in Fracture-Related Infection: A Consensus from an International Expert Group

Author: Depypere, M. (Melissa), Kuehl, R. (Richard), Metsemakers, W.-J. (Willem-Jan), Senneville, E. (Eric), McNally, M.A. (Martin), Obremskey, W.T. (William), Zimmerli, W. (Werner), Atkins, B.L. (Bridget), Trampuz, A. (Andrej), Depypere, M. (Melissa), Kuehl, R. (Richard), Metsemakers, W.-J. (Willem-Jan), Senneville, E. (Eric), McNally, M.A. (Martin), Obremskey, W.T. (William), Zimmerli, W. (Werner), Atkins, B.L. (Bridget), and Trampuz, A. (Andrej)
Abstract: Summary:Fracture-related infection (FRI) is a major complication in musculoskeletal trauma and one of the leading causes of morbidity. Standardization of general treatment strategies for FRI has been poor. One of the reasons is the heterogeneity in this patient population, including various anatomical locations, multiple fracture patterns, different degrees of soft-tissue injury, and different patient conditions. This variability makes treatment complex and hard to standardize. As these infections are biofilm-related, surgery remains the cornerstone of treatment, and this entails multiple key aspects (eg, fracture fixation, tissue sampling, debridement, and soft-tissue management). Another important aspect, which is sometimes less familiar to the orthopaedic trauma surgeon, is systemic antimicrobial therapy. The aim of this article is to summarize the available evidence and provide recommendations for systemic antimicrobial therapy with respect to FRI, based on the most recent literature combined with expert opinion.Level of Evidence:Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.
Published: 2020
Full Text: View/download PDF

105. A multi‐omics approach identifies key regulatory pathways induced by long‐term zinc supplementation in human primary retinal pigment epithelium

Author: Emri, E. (Eszter), Kortvely, E., Dammeier, S., Klose, F., Simpson, D., Hollander, A.I., Ueffing, M., Lengyel, I., Acar, E., Ajana, S., Arango‐gonzalez, B., Armento, A., Badura, F., Bartz‐schmidt, U., Biarnes, M., Borrell, A., de Breuk, A., De la Cerda, B., Colijn, J.M. (Johanna), Cougnard‐gregoire, A., Delcourt, C, Diether, S., Endermann, T., Ferraro, L.L., Garcia, M. (Melissa), Heesterbeek, T.J., Honisch, S., Kilger, E., Klaver, C.C.W. (Caroline), Langen, H., Meester‐smoor, M., Merle, B.M.J., Mones, J., Nogoceke, E., Peto, T. (Tünde), Pool, F.M., Rodríguez, P.M., Sousa, J., Thee, E., Verzijden, T., Zumbansen, M., Emri, E. (Eszter), Kortvely, E., Dammeier, S., Klose, F., Simpson, D., Hollander, A.I., Ueffing, M., Lengyel, I., Acar, E., Ajana, S., Arango‐gonzalez, B., Armento, A., Badura, F., Bartz‐schmidt, U., Biarnes, M., Borrell, A., de Breuk, A., De la Cerda, B., Colijn, J.M. (Johanna), Cougnard‐gregoire, A., Delcourt, C, Diether, S., Endermann, T., Ferraro, L.L., Garcia, M. (Melissa), Heesterbeek, T.J., Honisch, S., Kilger, E., Klaver, C.C.W. (Caroline), Langen, H., Meester‐smoor, M., Merle, B.M.J., Mones, J., Nogoceke, E., Peto, T. (Tünde), Pool, F.M., Rodríguez, P.M., Sousa, J., Thee, E., Verzijden, T., and Zumbansen, M.
Abstract: In age-related macular degeneration (AMD), both systemic and local zinc levels decline. Elevation of zinc in clinical studies delayed the progression to end-stage AMD. However, the molecular pathways underpinning this beneficial effect are not yet identified. In this study, we used differentiated primary human fetal retinal pigment epithelium (RPE) cultures and long-term zinc supplementation to carry out a combined transcriptome, proteome and secretome analysis from three genetically different human donors. After combining significant differences, we identified the complex molecular networks using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). The cell cultures from the three donors showed extensive pigmentation, development of microvilli and basal infoldings and responded to zinc supplementation with an increase in transepithelial electrical resistance (TEER) (apical supplementation: 443.2 ± 79.3%, basal supplementation: 424.9 ± 116.8%, compared to control: 317.5 ± 98.2%). Significant changes were observed in the expression of 1044 genes, 151 cellular proteins and 124 secreted proteins. Gene set enrichment analysis revealed changes in specific molecular pathways related to cell adhesion/polarity, extracellular matrix organization, protein processing/transport, and oxidative stress response by zinc and identified a key upstream regulator effect similar to that of TGFB1.
Published: 2020
Full Text: View/download PDF

106. Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Author: Bryant, L. (Laura), Li, D. (Dong), Cox, S.G. (Samuel G.), Marchione, D. (Dylan), Joiner, E.F. (Evan F.), Wilson, K. (Khadija), Janssen, K. (Kevin), Lee, P. (Pearl), March, K. (Keith), Nair, D. (Divya), Sherr, E. (Elliott), Fregeau, B. (Brieana), Wierenga, K.J. (Klaas J.), Wadley, A. (Alexandrea), Mancini, G.M.S. (Grazia), Powell-Hamilton, N. (Nina), Kamp, J.J.P. (Jacques) van de, Grebe, T. (Theresa), Dean, J. (John), Ross, A.J. (Alison), Crawford, H.P. (Heather P.), Powis, Z. (Zoe), Cho, M.T. (Megan T.), Willing, M.C. (Marcia C.), Manwaring, L. (Linda), Schot, R. (Rachel), Nava, C. (Caroline), Afenjar, A. (Alexandra), Lessel, D. (Davor), Wagner, M. (Matias), Klopstock, T. (Thomas), Winkelmann, B., Catarino, C.B. (Claudia B.), Retterer, K. (Kyle), Schuette, J.L. (Jane L.), Innis, J.W. (Jeffrey), Pizzino, A. (Amy), Lüttgen, S. (Sabine), Denecke, J. (Jonas), Strom, T.M. (Tim), Monaghan, K.G. (Kristin G.), Yuan, Z.-F. (Zuo-Fei), Dubbs, H. (Holly), Bend, R. (Renee), Lee, J.A. (Jennifer A.), Lyons, M.J. (Michael J.), Hoefele, J. (Julia), Günthner, R. (Roman), Reutter, H. (Heiko), Keren, B. (Boris), Radtke, K. (Kelly), Sherbini, O. (Omar), Mrokse, C. (Cameron), Helbig, K.L. (Katherine L.), Odent, S. (Sylvie), Cogne, B. (Benjamin), Mercier, S. (Sandra), Bezieau, S. (Stephane), Besnard, T. (Thomas), Kury, S. (Sebastien), Redon, R. (Richard), Reinson, K. (Karit), Wojcik, M.H. (Monica H.), Õunap, K. (Katrin), Ilves, P. (Pilvi), Innes, A.M. (A Micheil), Kernohan, K.D. (Kristin), Costain, G. (Gregory), Meyn, M.S. (M Stephen), Chitayat, D. (David), Zackai, E. (Elaine), Lehman, A. (Anna), Kitson, H. (Hilary), Martin, M.G. (Martin G.), Martinez-Agosto, J.A. (Julian A.), Nelson, S.F. (Stan F.), Palmer, C.G.S. (Christina G S), Papp, J.C. (Jeanette C.), Parker, N.H. (Neil H.), Sinsheimer, J.S. (Janet S.), Vilain, E. (Eric), Wan, J. (Jijun), Yoon, A.J. (Amanda J.), Zheng, A. (Allison), Brimble, E. (Elise), Ferrero, G.B. (Giovanni Battista), Radio, F.C. (Francesca Clementina), Carli, D. (Diana), Barresi, S. (Sabina), Brusco, A. (Alfredo), Tartaglia, M. (Marco), Thomas, J.M. (Jennifer Muncy), Umana, L. (Luis), Weiss, M.M. (Marjan M.), Gotway, G. (Garrett), Stuurman, K.E. (Kyra), Thompson, M.L. (Michelle L.), McWalter, K. (Kirsty), Stumpel, C.T.R.M. (Constance T R M), Stevens, S.J.C. (Servi J C), Stegmann, A.P.A. (Alexander P A), Tveten, K. (Kristian), Vøllo, A. (Arve), Prescott, T. (Trine), Fagerberg, C. (Christina), Laulund, L.W. (Lone Walentin), Larsen, M.J. (Martin J.), Byler, M. (Melissa), Lebel, R.R. (Robert Roger), Hurst, A.C. (Anna C.), Dean, J. (Joy), Schrier Vergano, S.A. (Samantha A.), Norman, J. (Jennifer), Mercimek-Andrews, S. (Saadet), Neira, J. (Juanita), Van Allen, M.I. (Margot I.), Longo, N. (Nicola), Sellars, E. (Elizabeth), Louie, R.J. (Raymond J.), Cathey, S.S. (Sara S.), Brokamp, E. (Elly), Héron, D. (Delphine), Snyder, M. (Molly), Vanderver, A. (Adeline), Simon, C. (Celeste), de la Cruz, X. (Xavier), Padilla, N. (Natália), Crump, J.G. (J Gage), Chung, W. (Wendy), Garcia, B. (Benjamin), Hakonarson, H. (Hakon), Bhoj, E.J. (Elizabeth J.), Bryant, L. (Laura), Li, D. (Dong), Cox, S.G. (Samuel G.), Marchione, D. (Dylan), Joiner, E.F. (Evan F.), Wilson, K. (Khadija), Janssen, K. (Kevin), Lee, P. (Pearl), March, K. (Keith), Nair, D. (Divya), Sherr, E. (Elliott), Fregeau, B. (Brieana), Wierenga, K.J. (Klaas J.), Wadley, A. (Alexandrea), Mancini, G.M.S. (Grazia), Powell-Hamilton, N. (Nina), Kamp, J.J.P. (Jacques) van de, Grebe, T. (Theresa), Dean, J. (John), Ross, A.J. (Alison), Crawford, H.P. (Heather P.), Powis, Z. (Zoe), Cho, M.T. (Megan T.), Willing, M.C. (Marcia C.), Manwaring, L. (Linda), Schot, R. (Rachel), Nava, C. (Caroline), Afenjar, A. (Alexandra), Lessel, D. (Davor), Wagner, M. (Matias), Klopstock, T. (Thomas), Winkelmann, B., Catarino, C.B. (Claudia B.), Retterer, K. (Kyle), Schuette, J.L. (Jane L.), Innis, J.W. (Jeffrey), Pizzino, A. (Amy), Lüttgen, S. (Sabine), Denecke, J. (Jonas), Strom, T.M. (Tim), Monaghan, K.G. (Kristin G.), Yuan, Z.-F. (Zuo-Fei), Dubbs, H. (Holly), Bend, R. (Renee), Lee, J.A. (Jennifer A.), Lyons, M.J. (Michael J.), Hoefele, J. (Julia), Günthner, R. (Roman), Reutter, H. (Heiko), Keren, B. (Boris), Radtke, K. (Kelly), Sherbini, O. (Omar), Mrokse, C. (Cameron), Helbig, K.L. (Katherine L.), Odent, S. (Sylvie), Cogne, B. (Benjamin), Mercier, S. (Sandra), Bezieau, S. (Stephane), Besnard, T. (Thomas), Kury, S. (Sebastien), Redon, R. (Richard), Reinson, K. (Karit), Wojcik, M.H. (Monica H.), Õunap, K. (Katrin), Ilves, P. (Pilvi), Innes, A.M. (A Micheil), Kernohan, K.D. (Kristin), Costain, G. (Gregory), Meyn, M.S. (M Stephen), Chitayat, D. (David), Zackai, E. (Elaine), Lehman, A. (Anna), Kitson, H. (Hilary), Martin, M.G. (Martin G.), Martinez-Agosto, J.A. (Julian A.), Nelson, S.F. (Stan F.), Palmer, C.G.S. (Christina G S), Papp, J.C. (Jeanette C.), Parker, N.H. (Neil H.), Sinsheimer, J.S. (Janet S.), Vilain, E. (Eric), Wan, J. (Jijun), Yoon, A.J. (Amanda J.), Zheng, A. (Allison), Brimble, E. (Elise), Ferrero, G.B. (Giovanni Battista), Radio, F.C. (Francesca Clementina), Carli, D. (Diana), Barresi, S. (Sabina), Brusco, A. (Alfredo), Tartaglia, M. (Marco), Thomas, J.M. (Jennifer Muncy), Umana, L. (Luis), Weiss, M.M. (Marjan M.), Gotway, G. (Garrett), Stuurman, K.E. (Kyra), Thompson, M.L. (Michelle L.), McWalter, K. (Kirsty), Stumpel, C.T.R.M. (Constance T R M), Stevens, S.J.C. (Servi J C), Stegmann, A.P.A. (Alexander P A), Tveten, K. (Kristian), Vøllo, A. (Arve), Prescott, T. (Trine), Fagerberg, C. (Christina), Laulund, L.W. (Lone Walentin), Larsen, M.J. (Martin J.), Byler, M. (Melissa), Lebel, R.R. (Robert Roger), Hurst, A.C. (Anna C.), Dean, J. (Joy), Schrier Vergano, S.A. (Samantha A.), Norman, J. (Jennifer), Mercimek-Andrews, S. (Saadet), Neira, J. (Juanita), Van Allen, M.I. (Margot I.), Longo, N. (Nicola), Sellars, E. (Elizabeth), Louie, R.J. (Raymond J.), Cathey, S.S. (Sara S.), Brokamp, E. (Elly), Héron, D. (Delphine), Snyder, M. (Molly), Vanderver, A. (Adeline), Simon, C. (Celeste), de la Cruz, X. (Xavier), Padilla, N. (Natália), Crump, J.G. (J Gage), Chung, W. (Wendy), Garcia, B. (Benjamin), Hakonarson, H. (Hakon), and Bhoj, E.J. (Elizabeth J.)
Abstract: Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation.
Published: 2020
Full Text: View/download PDF

107. Parental experiences of uncertainty following an abnormal fetal anomaly scan: Insights using Han’s taxonomy of uncertainty

Author: Hammond, J. (Jennifer), Klapwijk, J.E. (Jasmijn E.), Hill, M. (Melissa), Lou, S. (Stina), Ormond, K.E. (Kelly E.), Diderich, K.E.M. (Karin), Riedijk, S.R. (Samantha), Lewis, C. (Celine), Hammond, J. (Jennifer), Klapwijk, J.E. (Jasmijn E.), Hill, M. (Melissa), Lou, S. (Stina), Ormond, K.E. (Kelly E.), Diderich, K.E.M. (Karin), Riedijk, S.R. (Samantha), and Lewis, C. (Celine)
Abstract: For a number of prospective parents, uncertainty during pregnancy starts when an anomaly is found during a routine fetal anomaly scan. This may be followed by numerous tests to determine the etiology and nature of the anomaly. In this study, we aimed to understand how prospective parents perceive and manage uncertainty after being confronted with a structural anomaly during their routine ultrasound. Han's taxonomy of uncertainty was used as a framework to identify and understand the different types of uncertainty experienced. Interviews were held in the UK (n = 8 women and n = 1 male partner) and in the Netherlands (n = 7 women) with participants who had experienced uncertainty in their pregnancy after a fetal scan. Data were analyzed using thematic analysis, and the uncertainties experienced by parents were mapped against the dimensions of the Han taxonomy (sources, issues, and locus). Participants' experience of uncertainty was relevant to all dimensions and subcategories of the Han taxonomy, showing its applicability in the prenatal setting. Sources of uncertainty included receiving probabilistic o
Published: 2020
Full Text: View/download PDF

108. Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

Author: Liu, J. (Jingjing), Prager-van der Smissen, W.J.C. (Wendy), Collée, J.M. (J Margriet), Bolla, M.K. (Manjeet K.), Wang, Q. (Qin), Michailidou, K. (Kyriaki), Dennis, J. (Joe), Ahearn, T.U. (Thomas U.), Aittomäki, K. (Kristiina), Ambrosone, C.B. (Christine), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N.N. (Natalia N.), Arndt, V. (Volker), Arnold, N. (Norbert), Aronson, K.J. (Kristan J.), Augustinsson, A. (Annelie), Auvinen, P. (Päivi), Becher, H. (Heiko), Beckmann, M.W. (Matthias), Behrens, T.W. (Timothy), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Bogdanova, N.V. (Natalia V.), Bogdanova-Markov, N. (Nadja), Bojesen, S.E. (Stig), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Briceno, I. (Ignacio), Brucker, S.Y. (Sara Y.), Brüning, T. (Thomas), Burwinkel, B. (Barbara), Cai, Q. (Qiuyin), Cai, H. (Hui), Campa, D. (Daniele), Canzian, F. (Federico), Castelao, J.E. (Jose ), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Choi, J.-Y. (J.), Christiaens, M. (Melissa), Clarke, C. (Christine), Couch, F.J. (Fergus), Czene, K. (Kamila), Daly, M.B. (Mary), Devilee, P. (Peter), Santos Silva, I. (Isabel) dos, Dwek, M. (Miriam), Eccles, D.M. (Diana M.), Eliassen, A.H. (A Heather), Fasching, P.A. (Peter), Figueroa, J.D. (Jonine), Flyger, H. (Henrik), Fritschi, L. (Lin), Gago-Dominguez, M. (Manuela), Gapstur, S.M. (Susan M.), García-Closas, M. (Montserrat), García-Sáenz, J.A. (José A), Gaudet, M.M. (Mia M.), Giles, G.G. (Graham G.), Goldberg, M.S. (Mark), Radice, P. (Paolo), Guénel, P. (Pascal), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hall, P. (Per), Harrington, P.A. (Patricia A.), Hart, S.N. (Steven N.), Hartman, J.M. (Joost), Hillemanns, P. (Peter), Hopper, J.L. (John), Hou, M.-F. (Ming-Feng), Hunter, D.J. (David), Huo, D. (Dezheng), Ito, H. (Hidemi), Iwasaki, M. (Motoki), Jakimovska, M. (Milena), Jakubowska, A. (Anna), John, E.M. (Esther), Kaaks, R. (Rudolf), Kang, D. (Daehee), Keeman, R. (Renske), Khusnutdinova, E.K. (Elza), Kim, S.-W. (Sung-Won), Kraft, P. (Peter), Kristensen, V. (Vessela), Kurian, A.W. (Allison W.), Le Marchand, L. (Loic), Li, J. (Jingmei), Lindblom, A. (Annika), Lophatananon, A. (Artitaya), Luben, R.N. (Robert N.), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Manoukian, S. (Siranoush), Margolin, S. (Sara), Mariapun, S. (Shivaani), Matsuo, K. (Keitaro), Maurer, T. (Tabea), Mavroudis, D. (Dimitris), Meindl, A. (Alfons), Menon, U. (Usha), Milne, R.L. (Roger), Muir, K. (Kenneth), Mulligan, A.-M. (Anna-Marie), Floris, O.A.M., Nevanlinna, H. (Heli), Offit, K. (Kenneth), Olopade, O.I. (Olofunmilayo), Olson, J.E. (Janet), Olsson, H. (Håkan), Orr, N. (Nick), Park, S.K. (Sue K.), Peterlongo, P. (Paolo), Peto, J. (Julian), Plaseska-Karanfilska, D. (Dijana), Presneau, N. (Nadege), Rack, B. (Brigitte), Rau-Murthy, R. (Rohini), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Rhenius, V. (Valerie), Romero, A. (Atocha), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Schmutzler, R.K. (Rita), Schneeweiss, A. (Andreas), Scott, C.G. (Christopher G.), Shah, M. (Mitul), Shen, C.-Y. (Chen-Yang), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), Sohn, C. (Christof), Southey, M.C. (Melissa), Spinelli, J.J. (John J.), Tamimi, R. (Rulla), Tapper, W.J. (William J.), Teo, S.H. (Soo H.), Terry, M.B. (Mary Beth), Torres, D. (Diana), Truong, T. (Thérèse), Untch, M. (Michael), Vachon, C. (Celine), van Asperen, C.J. (Christi J.), Wolk, K. (Kerstin), Yamaji, T. (Taiki), Zheng, W. (Wei), Ziogas, A. (Argyrios), Ziv, E. (Elad), Torres-Mejía, G. (Gabriela), Dörk, T. (Thilo), Swerdlow, A.J. (Anthony ), Hamann, U. (Ute), Schmidt, M.K. (Marjanka), Dunning, A.M. (Alison M.), Pharoah, P.D.P. (Paul), Adamo, P. (Pio) d', Hooning, M.J. (Maartje J.), Martens, J.W.M. (John), Hollestelle, A. (Antoinette), Liu, J. (Jingjing), Prager-van der Smissen, W.J.C. (Wendy), Collée, J.M. (J Margriet), Bolla, M.K. (Manjeet K.), Wang, Q. (Qin), Michailidou, K. (Kyriaki), Dennis, J. (Joe), Ahearn, T.U. (Thomas U.), Aittomäki, K. (Kristiina), Ambrosone, C.B. (Christine), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Antonenkova, N.N. (Natalia N.), Arndt, V. (Volker), Arnold, N. (Norbert), Aronson, K.J. (Kristan J.), Augustinsson, A. (Annelie), Auvinen, P. (Päivi), Becher, H. (Heiko), Beckmann, M.W. (Matthias), Behrens, T.W. (Timothy), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Bogdanova, N.V. (Natalia V.), Bogdanova-Markov, N. (Nadja), Bojesen, S.E. (Stig), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Briceno, I. (Ignacio), Brucker, S.Y. (Sara Y.), Brüning, T. (Thomas), Burwinkel, B. (Barbara), Cai, Q. (Qiuyin), Cai, H. (Hui), Campa, D. (Daniele), Canzian, F. (Federico), Castelao, J.E. (Jose ), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Choi, J.-Y. (J.), Christiaens, M. (Melissa), Clarke, C. (Christine), Couch, F.J. (Fergus), Czene, K. (Kamila), Daly, M.B. (Mary), Devilee, P. (Peter), Santos Silva, I. (Isabel) dos, Dwek, M. (Miriam), Eccles, D.M. (Diana M.), Eliassen, A.H. (A Heather), Fasching, P.A. (Peter), Figueroa, J.D. (Jonine), Flyger, H. (Henrik), Fritschi, L. (Lin), Gago-Dominguez, M. (Manuela), Gapstur, S.M. (Susan M.), García-Closas, M. (Montserrat), García-Sáenz, J.A. (José A), Gaudet, M.M. (Mia M.), Giles, G.G. (Graham G.), Goldberg, M.S. (Mark), Radice, P. (Paolo), Guénel, P. (Pascal), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hall, P. (Per), Harrington, P.A. (Patricia A.), Hart, S.N. (Steven N.), Hartman, J.M. (Joost), Hillemanns, P. (Peter), Hopper, J.L. (John), Hou, M.-F. (Ming-Feng), Hunter, D.J. (David), Huo, D. (Dezheng), Ito, H. (Hidemi), Iwasaki, M. (Motoki), Jakimovska, M. (Milena), Jakubowska, A. (Anna), John, E.M. (Esther), Kaaks, R. (Rudolf), Kang, D. (Daehee), Keeman, R. (Renske), Khusnutdinova, E.K. (Elza), Kim, S.-W. (Sung-Won), Kraft, P. (Peter), Kristensen, V. (Vessela), Kurian, A.W. (Allison W.), Le Marchand, L. (Loic), Li, J. (Jingmei), Lindblom, A. (Annika), Lophatananon, A. (Artitaya), Luben, R.N. (Robert N.), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Manoukian, S. (Siranoush), Margolin, S. (Sara), Mariapun, S. (Shivaani), Matsuo, K. (Keitaro), Maurer, T. (Tabea), Mavroudis, D. (Dimitris), Meindl, A. (Alfons), Menon, U. (Usha), Milne, R.L. (Roger), Muir, K. (Kenneth), Mulligan, A.-M. (Anna-Marie), Floris, O.A.M., Nevanlinna, H. (Heli), Offit, K. (Kenneth), Olopade, O.I. (Olofunmilayo), Olson, J.E. (Janet), Olsson, H. (Håkan), Orr, N. (Nick), Park, S.K. (Sue K.), Peterlongo, P. (Paolo), Peto, J. (Julian), Plaseska-Karanfilska, D. (Dijana), Presneau, N. (Nadege), Rack, B. (Brigitte), Rau-Murthy, R. (Rohini), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Rhenius, V. (Valerie), Romero, A. (Atocha), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Schmutzler, R.K. (Rita), Schneeweiss, A. (Andreas), Scott, C.G. (Christopher G.), Shah, M. (Mitul), Shen, C.-Y. (Chen-Yang), Shu, X.-O. (Xiao-Ou), Simard, J. (Jacques), Sohn, C. (Christof), Southey, M.C. (Melissa), Spinelli, J.J. (John J.), Tamimi, R. (Rulla), Tapper, W.J. (William J.), Teo, S.H. (Soo H.), Terry, M.B. (Mary Beth), Torres, D. (Diana), Truong, T. (Thérèse), Untch, M. (Michael), Vachon, C. (Celine), van Asperen, C.J. (Christi J.), Wolk, K. (Kerstin), Yamaji, T. (Taiki), Zheng, W. (Wei), Ziogas, A. (Argyrios), Ziv, E. (Elad), Torres-Mejía, G. (Gabriela), Dörk, T. (Thilo), Swerdlow, A.J. (Anthony ), Hamann, U. (Ute), Schmidt, M.K. (Marjanka), Dunning, A.M. (Alison M.), Pharoah, P.D.P. (Paul), Adamo, P. (Pio) d', Hooning, M.J. (Maartje J.), Martens, J.W.M. (John), and Hollestelle, A. (Antoinette)
Abstract: In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
Published: 2020
Full Text: View/download PDF

109. Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

Author: Biemans, V.B.C. (Vince B. C.), Sleutjes, J.A.M. (Jasmijn A. M.), de Vries, A.C. (Annemarie C.), Bodelier, A. (Alexander), Dijkstra, G. (Gerard), Oldenburg, B. (Bas), Löwenberg, M., Bodegraven, A.A. (Ad) van, Meulen-de Jong, A.E. (Andrea) van der, Boer, K.H.N. (Nanne) de, Srivastava, N. (Nidhi), West, R.L. (Rachel), Römkens, T.E.H., Horjus Talabur Horje, C.S. (Carmen S.), Jansen, J.M. (Jeroen Michiel), van der Woude, C.J. (C. Janneke), Hoekstra, J. (Jildou), Weersma, R.K. (Rinse K.), Schaik, F.D.M. (Fiona) van, Hoentjen, F., Pierik, M. (Marieke), Fidder, M. (Melissa), Ponsioen, C.Y. (Cyril), Duijvestein, M. (Marjolijn), Romberg-Camps, M. (Mariëlle), Maljaars, P.W.J. (P. W.J.), Bouma, G. (Gerd), van der Marel, S. (S.), De Jong, D.J. (Dirk J.), Haans, J.J.L. (J. J.L.), Biemans, V.B.C. (Vince B. C.), Sleutjes, J.A.M. (Jasmijn A. M.), de Vries, A.C. (Annemarie C.), Bodelier, A. (Alexander), Dijkstra, G. (Gerard), Oldenburg, B. (Bas), Löwenberg, M., Bodegraven, A.A. (Ad) van, Meulen-de Jong, A.E. (Andrea) van der, Boer, K.H.N. (Nanne) de, Srivastava, N. (Nidhi), West, R.L. (Rachel), Römkens, T.E.H., Horjus Talabur Horje, C.S. (Carmen S.), Jansen, J.M. (Jeroen Michiel), van der Woude, C.J. (C. Janneke), Hoekstra, J. (Jildou), Weersma, R.K. (Rinse K.), Schaik, F.D.M. (Fiona) van, Hoentjen, F., Pierik, M. (Marieke), Fidder, M. (Melissa), Ponsioen, C.Y. (Cyril), Duijvestein, M. (Marjolijn), Romberg-Camps, M. (Mariëlle), Maljaars, P.W.J. (P. W.J.), Bouma, G. (Gerd), van der Marel, S. (S.), De Jong, D.J. (Dirk J.), and Haans, J.J.L. (J. J.L.)
Abstract: Background: Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). Aim: To evaluate effectiveness, safety and use of tofacitinib in daily practice. Methods: UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation. Results: In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9-26), 18% (95% CI 8-28) and 21% (95% CI 14-39) respectively. Conclusion: Tofacitinib is an effective treatment for UC after anti-TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients.
Published: 2020
Full Text: View/download PDF

110. An sRNA Screen for Reversal of Quinolone Resistance in Escherichia coli

Author: Bhatnagar, K. (Kamya), Hinz, A. (Aaron), Kohlman, M. (Melissa), Wong, A. (Alex), Bhatnagar, K. (Kamya), Hinz, A. (Aaron), Kohlman, M. (Melissa), and Wong, A. (Alex)
Abstract: In light of the rising prevalence of antimicrobial resistance (AMR) and the slow pace of new antimicrobial development, there has been increasing interest in the development of adjuvants that improve or restore the effectiveness of existing drugs. Here, we use a novel small RNA (sRNA) screening approach to identify genes whose knockdown increases ciprofloxacin (CIP) sensitivity in a resistant strain of Escherichia coli 5000 sRNA constructs were initially screened on a gyrA S83L background, ultimately leading to 30 validated genes whose disruption reduces CIP resistance. This set includes genes involved in DNA replication, repair, recombination, efflux, and other regulatory systems. Our findings increase understanding of the functional interactions of DNA Gyrase, and may aid in the development of new therapeutic approaches for combating AMR.
Published: 2020
Full Text: View/download PDF

111. MicroRNA expression and DNA methylation profiles do not distinguish between primary and recurrent well-differentiated liposarcoma

Author: Vos, M. (Melissa), Boers, R. (Ruben), Vriends, A.L.M. (Anne), Boers, J. (Joachim), Kuijk, P.F. (Patricia) van, Houdt, W.J. (Winan) van, Leenders, G.J.H.L. (Geert), Wagrodzki, M. (Michal), IJcken, W.F.J. (Wilfred) van, Gribnau, J.H. (Joost), Grunhagen, D.J. (Dirk Jan), Verhoef, C. (Kees), Sleijfer, S. (Stefan), Wiemer, E.A.C. (Erik), Vos, M. (Melissa), Boers, R. (Ruben), Vriends, A.L.M. (Anne), Boers, J. (Joachim), Kuijk, P.F. (Patricia) van, Houdt, W.J. (Winan) van, Leenders, G.J.H.L. (Geert), Wagrodzki, M. (Michal), IJcken, W.F.J. (Wilfred) van, Gribnau, J.H. (Joost), Grunhagen, D.J. (Dirk Jan), Verhoef, C. (Kees), Sleijfer, S. (Stefan), and Wiemer, E.A.C. (Erik)
Abstract: Approximately one-third of the patients with well-differentiated liposarcoma (WDLPS) will develop a local recurrence. Not much is known about the molecular relationship between the primary tumor and the recurrent tumor, which is important to reveal potential drivers of recurrence. Here we investigated the biology of recurrent WDLPS by comparing paired primary and recurrent WDLPS using microRNA profiling and genome-wide DNA methylation analyses. In total, 27 paired primary and recurrent WDLPS formalin-fixed and paraffin-embedded tumor samples were collected. MicroRNA expression profiles were determined using TaqMan® Low Density Array (TLDA) cards. Genome-wide DNA methylation and differentially methylated regions (DMRs) were assessed by methylated DNA sequencing (MeD-seq). A supervised cluster analysis based on differentially expressed microRNAs between paired primary and recurrent WDLPS did not reveal a clear cluster pattern separating the primary from the recurrent tumors. The clustering was also not based on tumor localization, time to recurrence, age or status of the resection margins. Changes in DNA methylation between primary and recurrent tumors were extremely variable, and no consistent DNA methylation changes were found. As a result, a supervised clustering analysis based on DMRs between primary and recurrent tumors did not show a distinct cluster pattern based on any of the features. Subgroup analysis for tumors localized in the extremity or the retroperitoneum also did not yield a clear distinction between primary and recurrent WDLPS samples. In conclusion, microRNA expression profiles and DNA methylation profiles do not distinguish between primary and recurrent WDLPS and no putative common drivers could be identified.
Published: 2020
Full Text: View/download PDF

112. Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals

Author: Surendran, P. (Praveen), Feofanova, E. V. (Elena, V), Lahrouchi, N. (Najim), Ntalla, I. (Ioanna), Karthikeyan, S. (Savita), Cook, J. (James), Chen, L. (Lingyan), Mifsud, B. (Borbala), Yao, C. (Chen), Kraja, A. T. (Aldi T.), Cartwright, J. H. (James H.), Hellwege, J. N. (Jacklyn N.), Giri, A. (Ayush), Tragante, V. (Vinicius), Thorleifsson, G. (Gudmar), Liu, D. J. (Dajiang J.), Prins, B. P. (Bram P.), Stewart, I. D. (Isobel D.), Cabrera, C. P. (Claudia P.), Eales, J. M. (James M.), Akbarov, A. (Artur), Auer, P. L. (Paul L.), Bielak, L. F. (Lawrence F.), Bis, J. C. (Joshua C.), Braithwaite, V. S. (Vickie S.), Brody, J. A. (Jennifer A.), Daw, E. W. (E. Warwick), Warren, H. R. (Helen R.), Drenos, F. (Fotios), Nielsen, S. F. (Sune Fallgaard), Faul, J. D. (Jessica D.), Fauman, E. B. (Eric B.), Fava, C. (Cristiano), Ferreira, T. (Teresa), Foley, C. N. (Christopher N.), Franceschini, N. (Nora), Gao, H. (He), Giannakopoulou, O. (Olga), Giulianini, F. (Franco), Gudbjartsson, D. F. (Daniel F.), Guo, X. (Xiuqing), Harris, S. E. (Sarah E.), Havulinna, A. S. (Aki S.), Helgadottir, A. (Anna), Huffman, J. E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Kanoni, S. (Stavroula), Kontto, J. (Jukka), Larson, M. G. (Martin G.), Li-Gao, R. (Ruifang), Lindstrom, J. (Jaana), Lotta, L. A. (Luca A.), Lu, Y. (Yingchang), Luan, J. (Jian'an), Mahajan, A. (Anubha), Malerba, G. (Giovanni), Masca, N. G. (Nicholas G. D.), Mei, H. (Hao), Menni, C. (Cristina), Mook-Kanamori, D. O. (Dennis O.), Mosen-Ansorena, D. (David), Muller-Nurasyid, M. (Martina), Pare, G. (Guillaume), Paul, D. S. (Dirk S.), Perola, M. (Markus), Poveda, A. (Alaitz), Rauramaa, R. (Rainer), Richard, M. (Melissa), Richardson, T. G. (Tom G.), Sepulveda, N. (Nuno), Sim, X. (Xueling), Smith, A. V. (Albert, V), Smith, J. A. (Jennifer A.), Staley, J. R. (James R.), Stanakova, A. (Alena), Sulem, P. (Patrick), Theriault, S. (Sebastien), Thorsteinsdottir, U. (Unnur), Trompet, S. (Stella), Varga, T. V. (Tibor V.), Edwards, D. R. (Digna R. Velez), Veronesi, G. (Giovanni), Weiss, S. (Stefan), Willems, S. M. (Sara M.), Yao, J. (Jie), Young, R. (Robin), Yu, B. (Bing), Zhang, W. (Weihua), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Evangelou, E. (Evangelos), Aeschbacher, S. (Stefanie), Asllanaj, E. (Eralda), Blankenberg, S. (Stefan), Bonnycastle, L. L. (Lori L.), Bork-Jensen, J. (Jette), Brandslund, I. (Ivan), Braund, P. S. (Peter S.), Burgess, S. (Stephen), Cho, K. (Kelly), Christensen, C. (Cramer), Connell, J. (John), de Mutsert, R. (Renee), Dominiczak, A. F. (Anna F.), Dorr, M. (Marcus), Eiriksdottir, G. (Gudny), Farmaki, A.-E. (Aliki-Eleni), Gaziano, J. M. (J. Michael), Grarup, N. (Niels), Grove, M. L. (Megan L.), Hallmans, G. (Goran), Hansen, T. (Torben), Have, C. T. (Christian T.), Heiss, G. (Gerardo), Jorgensen, M. E. (Marit E.), Jousilahti, P. (Pekka), Kajantie, E. (Eero), Kamat, M. (Mihir), Karajamaki, A. (AnneMari), Karpe, F. (Fredrik), Koistinen, H. A. (Heikki A.), Kovesdy, C. P. (Csaba P.), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Lannfelt, L. (Lars), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Linneberg, A. (Allan), Martin, L. W. (Lisa W.), Moitry, M. (Marie), Nadkarni, G. (Girish), Neville, M. J. (Matt J.), Palmer, C. N. (Colin N. A.), Papanicolaou, G. J. (George J.), Pedersen, O. (Oluf), Peters, J. (James), Poulter, N. (Neil), Rasheed, A. (Asif), Rasmussen, K. L. (Katrine L.), Rayner, N. W. (N. William), Magi, R. (Reedik), Renstrom, F. (Frida), Rettig, R. (Rainer), Rossouw, J. (Jacques), Schreiner, P. J. (Pamela J.), Sever, P. S. (Peter S.), Sigurdsson, E. L. (Emil L.), Skaaby, T. (Tea), Sun, Y. V. (Yan, V), Sundstrom, J. (Johan), Thorgeirsson, G. (Gudmundur), Esko, T. (Tonu), Trabetti, E. (Elisabetta), Tsao, P. S. (Philip S.), Tuomi, T. (Tiinamaija), Turner, S. T. (Stephen T.), Tzoulaki, I. (Ioanna), Vaartjes, I. (Ilonca), Vergnaud, A.-C. (Anne-Claire), Willer, C. J. (Cristen J.), Wilson, P. W. (Peter W. F.), Witte, D. R. (Daniel R.), Yonova-Doing, E. (Ekaterina), Zhang, H. (He), Aliya, N. (Naheed), Almgren, P. (Peter), Amouyel, P. (Philippe), Asselbergs, F. W. (Folkert W.), Barnes, M. R. (Michael R.), Blakemore, A. I. (Alexandra, I), Boehnke, M. (Michael), Bots, M. L. (Michiel L.), Bottinger, E. P. (Erwin P.), Buring, J. E. (Julie E.), Chambers, J. C. (John C.), Chen, Y. I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Conen, D. (David), Correa, A. (Adolfo), Smith, G. D. (George Davey), de Boer, R. A. (Rudolf A.), Deary, I. J. (Ian J.), Dedoussis, G. (George), Deloukas, P. (Panos), Di Angelantonio, E. (Emanuele), Elliott, P. (Paul), Felix, S. B. (Stephan B.), Ferrieres, J. (Jean), Ford, I. (Ian), Fornage, M. (Myriam), Franks, P. W. (Paul W.), Franks, S. (Stephen), Frossard, P. (Philippe), Gambaro, G. (Giovanni), Gaunt, T. R. (Tom R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Harris, T. B. (Tamara B.), Hayward, C. (Caroline), Hennig, B. J. (Branwen J.), Herzig, K.-H. (Karl-Heinz), Ingelsson, E. (Erik), Tuomilehto, J. (Jaakko), Järvelin, M.-R. (Marjo-Riitta), Jukema, J. W. (J. Wouter), Kardia, S. L. (Sharon L. R.), Kee, F. (Frank), Kooner, J. S. (Jaspal S.), Kooperberg, C. (Charles), Launer, L. J. (Lenore J.), Lind, L. (Lars), Loos, R. J. (Ruth J. F.), Majumder, A. A. (Abdulla Al Shafi), Laakso, M. (Markku), McCarthy, M. I. (Mark, I), Melander, O. (Olle), Mohlke, K. L. (Karen L.), Murray, A. D. (Alison D.), Nordestgaard, B. G. (Borge Gronne), Orho-Melander, M. (Marju), Packard, C. J. (Chris J.), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Polasek, O. (Ozren), Porteous, D. J. (David J.), Prentice, A. M. (Andrew M.), Province, M. A. (Michael A.), Relton, C. L. (Caroline L.), Rice, K. (Kenneth), Ridker, P. M. (Paul M.), Rolandsson, O. (Olov), Rosendaal, F. R. (Frits R.), Rotter, J. I. (Jerome, I), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N. J. (Nilesh J.), Sattar, N. (Naveed), Sheu, W. H. (Wayne H-H), Smith, B. H. (Blair H.), Soranzo, N. (Nicole), Spector, T. D. (Timothy D.), Starr, J. M. (John M.), Sebert, S. (Sylvain), Taylor, K. D. (Kent D.), Lakka, T. A. (Timo A.), Timpson, N. J. (Nicholas J.), Tobin, M. D. (Martin D.), van der Harst, P. (Pim), van der Meer, P. (Peter), Ramachandran, V. S. (Vasan S.), Verweij, N. (Niek), Virtamo, J. (Jarmo), Volker, U. (Uwe), Weir, D. R. (David R.), Zeggini, E. (Eleftheria), Charchar, F. J. (Fadi J.), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Tomaszewski, M. (Maciej), Butterworth, A. S. (Adam S.), Caulfield, M. J. (Mark J.), Danesh, J. (John), Edwards, T. L. (Todd L.), Holm, H. (Hilma), Hung, A. M. (Adriana M.), Lindgren, C. M. (Cecilia M.), Liu, C. (Chunyu), Manning, A. K. (Alisa K.), Morris, A. P. (Andrew P.), Morrison, A. C. (Alanna C.), O'Donnell, C. J. (Christopher J.), Psaty, B. M. (Bruce M.), Saleheen, D. (Danish), Stefansson, K. (Kari), Boerwinkle, E. (Eric), Chasman, D. I. (Daniel, I), Levy, D. (Daniel), Newton-Cheh, C. (Christopher), Munroe, P. B. (Patricia B.), Howson, J. M. (Joanna M. M.), Surendran, P. (Praveen), Feofanova, E. V. (Elena, V), Lahrouchi, N. (Najim), Ntalla, I. (Ioanna), Karthikeyan, S. (Savita), Cook, J. (James), Chen, L. (Lingyan), Mifsud, B. (Borbala), Yao, C. (Chen), Kraja, A. T. (Aldi T.), Cartwright, J. H. (James H.), Hellwege, J. N. (Jacklyn N.), Giri, A. (Ayush), Tragante, V. (Vinicius), Thorleifsson, G. (Gudmar), Liu, D. J. (Dajiang J.), Prins, B. P. (Bram P.), Stewart, I. D. (Isobel D.), Cabrera, C. P. (Claudia P.), Eales, J. M. (James M.), Akbarov, A. (Artur), Auer, P. L. (Paul L.), Bielak, L. F. (Lawrence F.), Bis, J. C. (Joshua C.), Braithwaite, V. S. (Vickie S.), Brody, J. A. (Jennifer A.), Daw, E. W. (E. Warwick), Warren, H. R. (Helen R.), Drenos, F. (Fotios), Nielsen, S. F. (Sune Fallgaard), Faul, J. D. (Jessica D.), Fauman, E. B. (Eric B.), Fava, C. (Cristiano), Ferreira, T. (Teresa), Foley, C. N. (Christopher N.), Franceschini, N. (Nora), Gao, H. (He), Giannakopoulou, O. (Olga), Giulianini, F. (Franco), Gudbjartsson, D. F. (Daniel F.), Guo, X. (Xiuqing), Harris, S. E. (Sarah E.), Havulinna, A. S. (Aki S.), Helgadottir, A. (Anna), Huffman, J. E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Kanoni, S. (Stavroula), Kontto, J. (Jukka), Larson, M. G. (Martin G.), Li-Gao, R. (Ruifang), Lindstrom, J. (Jaana), Lotta, L. A. (Luca A.), Lu, Y. (Yingchang), Luan, J. (Jian'an), Mahajan, A. (Anubha), Malerba, G. (Giovanni), Masca, N. G. (Nicholas G. D.), Mei, H. (Hao), Menni, C. (Cristina), Mook-Kanamori, D. O. (Dennis O.), Mosen-Ansorena, D. (David), Muller-Nurasyid, M. (Martina), Pare, G. (Guillaume), Paul, D. S. (Dirk S.), Perola, M. (Markus), Poveda, A. (Alaitz), Rauramaa, R. (Rainer), Richard, M. (Melissa), Richardson, T. G. (Tom G.), Sepulveda, N. (Nuno), Sim, X. (Xueling), Smith, A. V. (Albert, V), Smith, J. A. (Jennifer A.), Staley, J. R. (James R.), Stanakova, A. (Alena), Sulem, P. (Patrick), Theriault, S. (Sebastien), Thorsteinsdottir, U. (Unnur), Trompet, S. (Stella), Varga, T. V. (Tibor V.), Edwards, D. R. (Digna R. Velez), Veronesi, G. (Giovanni), Weiss, S. (Stefan), Willems, S. M. (Sara M.), Yao, J. (Jie), Young, R. (Robin), Yu, B. (Bing), Zhang, W. (Weihua), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Evangelou, E. (Evangelos), Aeschbacher, S. (Stefanie), Asllanaj, E. (Eralda), Blankenberg, S. (Stefan), Bonnycastle, L. L. (Lori L.), Bork-Jensen, J. (Jette), Brandslund, I. (Ivan), Braund, P. S. (Peter S.), Burgess, S. (Stephen), Cho, K. (Kelly), Christensen, C. (Cramer), Connell, J. (John), de Mutsert, R. (Renee), Dominiczak, A. F. (Anna F.), Dorr, M. (Marcus), Eiriksdottir, G. (Gudny), Farmaki, A.-E. (Aliki-Eleni), Gaziano, J. M. (J. Michael), Grarup, N. (Niels), Grove, M. L. (Megan L.), Hallmans, G. (Goran), Hansen, T. (Torben), Have, C. T. (Christian T.), Heiss, G. (Gerardo), Jorgensen, M. E. (Marit E.), Jousilahti, P. (Pekka), Kajantie, E. (Eero), Kamat, M. (Mihir), Karajamaki, A. (AnneMari), Karpe, F. (Fredrik), Koistinen, H. A. (Heikki A.), Kovesdy, C. P. (Csaba P.), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Lannfelt, L. (Lars), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Linneberg, A. (Allan), Martin, L. W. (Lisa W.), Moitry, M. (Marie), Nadkarni, G. (Girish), Neville, M. J. (Matt J.), Palmer, C. N. (Colin N. A.), Papanicolaou, G. J. (George J.), Pedersen, O. (Oluf), Peters, J. (James), Poulter, N. (Neil), Rasheed, A. (Asif), Rasmussen, K. L. (Katrine L.), Rayner, N. W. (N. William), Magi, R. (Reedik), Renstrom, F. (Frida), Rettig, R. (Rainer), Rossouw, J. (Jacques), Schreiner, P. J. (Pamela J.), Sever, P. S. (Peter S.), Sigurdsson, E. L. (Emil L.), Skaaby, T. (Tea), Sun, Y. V. (Yan, V), Sundstrom, J. (Johan), Thorgeirsson, G. (Gudmundur), Esko, T. (Tonu), Trabetti, E. (Elisabetta), Tsao, P. S. (Philip S.), Tuomi, T. (Tiinamaija), Turner, S. T. (Stephen T.), Tzoulaki, I. (Ioanna), Vaartjes, I. (Ilonca), Vergnaud, A.-C. (Anne-Claire), Willer, C. J. (Cristen J.), Wilson, P. W. (Peter W. F.), Witte, D. R. (Daniel R.), Yonova-Doing, E. (Ekaterina), Zhang, H. (He), Aliya, N. (Naheed), Almgren, P. (Peter), Amouyel, P. (Philippe), Asselbergs, F. W. (Folkert W.), Barnes, M. R. (Michael R.), Blakemore, A. I. (Alexandra, I), Boehnke, M. (Michael), Bots, M. L. (Michiel L.), Bottinger, E. P. (Erwin P.), Buring, J. E. (Julie E.), Chambers, J. C. (John C.), Chen, Y. I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Conen, D. (David), Correa, A. (Adolfo), Smith, G. D. (George Davey), de Boer, R. A. (Rudolf A.), Deary, I. J. (Ian J.), Dedoussis, G. (George), Deloukas, P. (Panos), Di Angelantonio, E. (Emanuele), Elliott, P. (Paul), Felix, S. B. (Stephan B.), Ferrieres, J. (Jean), Ford, I. (Ian), Fornage, M. (Myriam), Franks, P. W. (Paul W.), Franks, S. (Stephen), Frossard, P. (Philippe), Gambaro, G. (Giovanni), Gaunt, T. R. (Tom R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Harris, T. B. (Tamara B.), Hayward, C. (Caroline), Hennig, B. J. (Branwen J.), Herzig, K.-H. (Karl-Heinz), Ingelsson, E. (Erik), Tuomilehto, J. (Jaakko), Järvelin, M.-R. (Marjo-Riitta), Jukema, J. W. (J. Wouter), Kardia, S. L. (Sharon L. R.), Kee, F. (Frank), Kooner, J. S. (Jaspal S.), Kooperberg, C. (Charles), Launer, L. J. (Lenore J.), Lind, L. (Lars), Loos, R. J. (Ruth J. F.), Majumder, A. A. (Abdulla Al Shafi), Laakso, M. (Markku), McCarthy, M. I. (Mark, I), Melander, O. (Olle), Mohlke, K. L. (Karen L.), Murray, A. D. (Alison D.), Nordestgaard, B. G. (Borge Gronne), Orho-Melander, M. (Marju), Packard, C. J. (Chris J.), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Polasek, O. (Ozren), Porteous, D. J. (David J.), Prentice, A. M. (Andrew M.), Province, M. A. (Michael A.), Relton, C. L. (Caroline L.), Rice, K. (Kenneth), Ridker, P. M. (Paul M.), Rolandsson, O. (Olov), Rosendaal, F. R. (Frits R.), Rotter, J. I. (Jerome, I), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N. J. (Nilesh J.), Sattar, N. (Naveed), Sheu, W. H. (Wayne H-H), Smith, B. H. (Blair H.), Soranzo, N. (Nicole), Spector, T. D. (Timothy D.), Starr, J. M. (John M.), Sebert, S. (Sylvain), Taylor, K. D. (Kent D.), Lakka, T. A. (Timo A.), Timpson, N. J. (Nicholas J.), Tobin, M. D. (Martin D.), van der Harst, P. (Pim), van der Meer, P. (Peter), Ramachandran, V. S. (Vasan S.), Verweij, N. (Niek), Virtamo, J. (Jarmo), Volker, U. (Uwe), Weir, D. R. (David R.), Zeggini, E. (Eleftheria), Charchar, F. J. (Fadi J.), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Tomaszewski, M. (Maciej), Butterworth, A. S. (Adam S.), Caulfield, M. J. (Mark J.), Danesh, J. (John), Edwards, T. L. (Todd L.), Holm, H. (Hilma), Hung, A. M. (Adriana M.), Lindgren, C. M. (Cecilia M.), Liu, C. (Chunyu), Manning, A. K. (Alisa K.), Morris, A. P. (Andrew P.), Morrison, A. C. (Alanna C.), O'Donnell, C. J. (Christopher J.), Psaty, B. M. (Bruce M.), Saleheen, D. (Danish), Stefansson, K. (Kari), Boerwinkle, E. (Eric), Chasman, D. I. (Daniel, I), Levy, D. (Daniel), Newton-Cheh, C. (Christopher), Munroe, P. B. (Patricia B.), and Howson, J. M. (Joanna M. M.)
Abstract: Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 x 10(⁻⁸)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets., Correction A Publisher Correction to this article was published on 16 March 2021.
Published: 2020

113. Metabolic profiling of formalin-fixed paraffin-embedded tissues discriminates normal colon from colorectal cancer

Author: Arima, K. (Kota), Lau, M. C. (Mai Chan), Zhao, M. (Melissa), Haruki, K. (Koichiro), Kosumi, K. (Keisuke), Mima, K. (Kosuke), Gu, M. (Mancang), Väyrynen, J. P. (Juha P.), Twombly, T. S. (Tyler S.), Baba, Y. (Yoshifumi), Fujiyoshi, K. (Kenji), Kishikawa, J. (Junko), Guo, C. (Chunguang), Baba, H. (Hideo), Richards, W. G. (William G.), Chan, A. T. (Andrew T.), Nishihara, R. (Reiko), Meyerhardt, J. A. (Jeffrey A.), Nowak, J. A. (Jonathan A.), Giannakis, M. (Marios), Fuchs, C. S. (Charles S.), Ogino, S. (Shuji), Arima, K. (Kota), Lau, M. C. (Mai Chan), Zhao, M. (Melissa), Haruki, K. (Koichiro), Kosumi, K. (Keisuke), Mima, K. (Kosuke), Gu, M. (Mancang), Väyrynen, J. P. (Juha P.), Twombly, T. S. (Tyler S.), Baba, Y. (Yoshifumi), Fujiyoshi, K. (Kenji), Kishikawa, J. (Junko), Guo, C. (Chunguang), Baba, H. (Hideo), Richards, W. G. (William G.), Chan, A. T. (Andrew T.), Nishihara, R. (Reiko), Meyerhardt, J. A. (Jeffrey A.), Nowak, J. A. (Jonathan A.), Giannakis, M. (Marios), Fuchs, C. S. (Charles S.), and Ogino, S. (Shuji)
Abstract: Accumulating evidence suggests that metabolic reprogramming has a critical role in carcinogenesis and tumor progression. The usefulness of formalin-fixed paraffin-embedded (FFPE) tissue material for metabolomics analysis as compared with fresh frozen tissue material remains unclear. LC/MS-MS–based metabolomics analysis was performed on 11 pairs of matched tumor and normal tissues in both FFPE and fresh frozen tissue materials from patients with colorectal carcinoma. Permutation t test was applied to identify metabolites with differential abundance between tumor and normal tissues. A total of 200 metabolites were detected in the FFPE samples and 536 in the fresh frozen samples. The preservation of metabolites in FFPE samples was diverse according to classes and chemical characteristics, ranging from 78% (energy) to 0% (peptides). Compared with the normal tissues, 34 (17%) and 174 (32%) metabolites were either accumulated or depleted in the tumor tissues derived from FFPE and fresh frozen samples, respectively. Among them, 15 metabolites were common in both FFPE and fresh frozen samples. Notably, branched chain amino acids were highly accumulated in tumor tissues. Using KEGG pathway analyses, glyoxylate and dicarboxylate metabolism, arginine and proline, glycerophospholipid, and glycine, serine, and threonine metabolism pathways distinguishing tumor from normal tissues were found in both FFPE and fresh frozen samples. This study demonstrates that informative data of metabolic profiles can be retrieved from FFPE tissue materials.
Published: 2020

114. Smoking status at diagnosis and colorectal cancer prognosis according to tumor lymphocytic reaction

Author: Fujiyoshi, K. (Kenji), Chen, Y. (Yang), Haruki, K. (Koichiro), Ugai, T. (Tomotaka), Kishikawa, J. (Junko), Hamada, T. (Tsuyoshi), Liu, L. (Li), Arima, K. (Kota), Borowsky, J. (Jennifer), Väyrynen, J. P. (Juha P.), Zhao, M. (Melissa), Lau, M. C. (Mai Chan), Gu, S. (Simeng), Shi, S. (Shanshan), Akimoto, N. (Naohiko), Twombly, T. S. (Tyler S.), Drew, D. A. (David A.), Song, M. (Mingyang), Chan, A. T. (Andrew T.), Giovannucci, E. L. (Edward L.), Meyerhardt, J. A. (Jeffrey A.), Fuchs, C. S. (Charles S.), Nishihara, R. (Reiko), Lennerz, J. K. (Jochen K.), Giannakis, M. (Marios), Nowak, J. A. (Jonathan A.), Zhang, X. (Xuehong), Wu, K. (Kana), Ogino, S. (Shuji), Fujiyoshi, K. (Kenji), Chen, Y. (Yang), Haruki, K. (Koichiro), Ugai, T. (Tomotaka), Kishikawa, J. (Junko), Hamada, T. (Tsuyoshi), Liu, L. (Li), Arima, K. (Kota), Borowsky, J. (Jennifer), Väyrynen, J. P. (Juha P.), Zhao, M. (Melissa), Lau, M. C. (Mai Chan), Gu, S. (Simeng), Shi, S. (Shanshan), Akimoto, N. (Naohiko), Twombly, T. S. (Tyler S.), Drew, D. A. (David A.), Song, M. (Mingyang), Chan, A. T. (Andrew T.), Giovannucci, E. L. (Edward L.), Meyerhardt, J. A. (Jeffrey A.), Fuchs, C. S. (Charles S.), Nishihara, R. (Reiko), Lennerz, J. K. (Jochen K.), Giannakis, M. (Marios), Nowak, J. A. (Jonathan A.), Zhang, X. (Xuehong), Wu, K. (Kana), and Ogino, S. (Shuji)
Abstract: Background: Smoking has been associated with worse colorectal cancer patient survival and may potentially suppress the immune response in the tumor microenvironment. We hypothesized that the prognostic association of smoking behavior at colorectal cancer diagnosis might differ by lymphocytic reaction patterns in cancer tissue. Methods: Using 1474 colon and rectal cancer patients within 2 large prospective cohort studies (Nurses’ Health Study and Health Professionals Follow-up Study), we characterized 4 patterns of histopathologic lymphocytic reaction, including tumor-infiltrating lymphocytes (TILs), intratumoral periglandular reaction, peritumoral lymphocytic reaction, and Crohn’s-like lymphoid reaction. Using covariate data of 4420 incident colorectal cancer patients in total, an inverse probability weighted multivariable Cox proportional hazards regression model was conducted to adjust for selection bias due to tissue availability and potential confounders, including tumor differentiation, disease stage, microsatellite instability status, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Results: The prognostic association of smoking status at diagnosis differed by TIL status. Compared with never smokers, the multivariable-adjusted colorectal cancer–specific mortality hazard ratio for current smokers was 1.50 (95% confidence interval = 1.10 to 2.06) in tumors with negative or low TIL and 0.43 (95% confidence interval = 0.16 to 1.12) in tumors with intermediate or high TIL (2-sided Pinteraction = 0.009). No statistically significant interactions were observed in the other patterns of lymphocytic reaction. Conclusions: The association of smoking status at diagnosis with colorectal cancer mortality may be stronger for carcinomas with negative or low TIL, suggesting a potential interplay of smoking and lymphocytic reaction in the colorectal cancer microenvironment.
Published: 2020

115. Tumour budding, poorly differentiated clusters, and T-cell response in colorectal cancer

Author: Fujiyoshi, K. (Kenji), Väyrynen, J. P. (Juha P.), Borowsky, J. (Jennifer), Papke, D. J. (David J., Jr.), Arima, K. (Kota), Haruki, K. (Koichiro), Kishikawa, J. (Junko), Akimoto, N. (Naohiko), Ugai, T. (Tomotaka), Lau, M. C. (Mai Chan), Gu, S. (Simeng), Shi, S. (Shanshan), Zhao, M. (Melissa), Da Silva, A. F. (Annacarolina Fabiana Lucia), Twombly, T. S. (Tyler S.), Nan, H. (Hongmei), Meyerhardt, J. A. (Jeffrey A.), Song, M. (Mingyang), Zhang, X. (Xuehong), Wu, K. (Kana), Chan, A. T. (Andrew T.), Fuchs, C. S. (Charles S.), Lennerz, J. K. (Jochen K.), Giannakis, M. (Marios), Nowak, J. A. (Jonathan A.), Ogino, S. (Shuji), Fujiyoshi, K. (Kenji), Väyrynen, J. P. (Juha P.), Borowsky, J. (Jennifer), Papke, D. J. (David J., Jr.), Arima, K. (Kota), Haruki, K. (Koichiro), Kishikawa, J. (Junko), Akimoto, N. (Naohiko), Ugai, T. (Tomotaka), Lau, M. C. (Mai Chan), Gu, S. (Simeng), Shi, S. (Shanshan), Zhao, M. (Melissa), Da Silva, A. F. (Annacarolina Fabiana Lucia), Twombly, T. S. (Tyler S.), Nan, H. (Hongmei), Meyerhardt, J. A. (Jeffrey A.), Song, M. (Mingyang), Zhang, X. (Xuehong), Wu, K. (Kana), Chan, A. T. (Andrew T.), Fuchs, C. S. (Charles S.), Lennerz, J. K. (Jochen K.), Giannakis, M. (Marios), Nowak, J. A. (Jonathan A.), and Ogino, S. (Shuji)
Abstract: Background/Objectives: Tumour budding and poorly differentiated clusters (PDC) represent forms of tumour invasion. We hypothesised that T-cell densities (reflecting adaptive anti-tumour immunity) might be inversely associated with tumour budding and PDC in colorectal carcinoma. Methods: Utilising 915 colon and rectal carcinomas in two U.S.-wide prospective cohort studies, and multiplex immunofluorescence combined with machine learning algorithms, we assessed CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3 co-expression patterns in lymphocytes. Tumour budding and PDC at invasive fronts were quantified by digital pathology and image analysis using the International tumour Budding Consensus Conference criteria. Using covariate data of 4,420 incident colorectal cancer cases, inverse probability weighting (IPW) was integrated with multivariable logistic regression analysis that assessed the association of T-cell subset densities with tumour budding and PDC while adjusting for selection bias due to tissue availability and potential confounders, including microsatellite instability status. Findings: Tumour budding counts were inversely associated with density of CD3+CD8+ [lowest vs. highest: multivariable odds ratio (OR), 0.50; 95% confidence interval (CI), 0.35–0.70; Ptrend < 0.001] and CD3+CD8+CD45RO+ cells (lowest vs. highest: multivariable OR, 0.44; 95% CI, 0.31–0.63; Ptrend < 0.001) in tumour epithelial region. Tumour budding levels were associated with higher colorectal cancer-specific mortality (multivariable hazard ratio, 2.13; 95% CI, 1.57–2.89; Ptrend < 0.001) in Cox regression analysis. There were no significant associations of PDC with T-cell subsets. Interpretation: Tumour epithelial naïve and memory cytotoxic T cell densities are inversely associated with tumour budding at invasive fronts, suggesting that cytotoxic anti-tumour immunity suppresses tumour microinvasion.
Published: 2020

116. Griffithsin carrageenan fast dissolving inserts prevent SHIV HSV-2 and HPV infections in vivo

Author: Brooke Grasperge, James Blanchard, Jeffrey D. Lifson, Michael Benson, Nina Derby, José A. Fernández-Romero, Olga Mizenina, Walid Heneine, M. Melissa Peet, Zachary Lloyd, Aixa Rodriguez, Shweta R. Ugaonkar, Meropi Aravantinou, Agegnehu Gettie, Thomas M. Zydowsky, Patrick Barnable, Manshun Lai, Manjari Lal, Asa Wesenberg, Melissa Robbiani, Natalia Teleshova, Barry R. O'Keefe, Larisa Kizima, Elena Martinelli, Kyle R. Kleinbeck, and Keith Levendosky
Subjects: Male, 0301 basic medicine, Herpesvirus 2, Human, animal diseases, Drug Evaluation, Preclinical, Simian Acquired Immunodeficiency Syndrome, General Physics and Astronomy, Drug resistance, HSL and HSV, Carrageenan, chemistry.chemical_compound, lcsh:Science, Griffithsin, Multidisciplinary, biology, Plants, Genetically Modified, Safety profile, Treatment Outcome, Vagina, Female, Simian Immunodeficiency Virus, Plant Lectins, medicine.drug, Drug Compounding, Science, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, In vivo, Tobacco, medicine, Animals, Humans, Acquired Immunodeficiency Syndrome, Herpes Genitalis, business.industry, Papillomavirus Infections, General Chemistry, Macaca mulatta, Virology, In vitro, Entry inhibitor, Administration, Intravaginal, Disease Models, Animal, Freeze Drying, 030104 developmental biology, chemistry, biology.protein, Pre-Exposure Prophylaxis, lcsh:Q, business
Abstract: Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) strategies with proven in vivo efficacy rely on antiretroviral drugs, creating the potential for drug resistance and complicated treatment options in individuals who become infected. Moreover, on-demand products are currently missing from the PrEP development portfolio. Griffithsin (GRFT) is a non-antiretroviral HIV entry inhibitor derived from red algae with an excellent safety profile and potent activity in vitro. When combined with carrageenan (CG), GRFT has strong activity against herpes simplex virus-2 (HSV-2) and human papillomavirus (HPV) in vitro and in vivo. Here, we report that GRFT/CG in a freeze-dried fast dissolving insert (FDI) formulation for on-demand use protects rhesus macaques from a high dose vaginal SHIV SF162P3 challenge 4 h after FDI insertion. Furthermore, the GRFT/CG FDI also protects mice vaginally against HSV-2 and HPV pseudovirus. As a safe, potent, broad-spectrum, on-demand non-antiretroviral product, the GRFT/CG FDI warrants clinical development.
Published: 2018

117. Feasibility of Using a Head-Mounted Camera to Capture Dynamic Facial Expressions During Body Movement

Author: Crane, Elizabeth A., primary, Gross, M. Melissa, additional, and Fredrickson, Barbara L., additional
Published: 2011
Full Text: View/download PDF

118. Pharmacokinetics of a weekly transdermal delivery system of tenofovir alafenamide in hairless rats

Author: Jiang, Ying, primary, Gao, Xinyi, additional, Singh, Onkar N., additional, Zhang, Wei, additional, Agrahari, Vivek, additional, Peet, M. Melissa, additional, Clark, Meredith R., additional, Doncel, Gustavo F., additional, and Banga, Ajay K., additional
Published: 2020
Full Text: View/download PDF

119. Inhibition of Glucosyltransferase Activity and Glucan Production as an Antibiofilm Mechanism of Lemongrass Essential Oil against Escherichia coli O157:H7

Author: Ortega-Ramirez, Luis A., primary, Gutiérrez-Pacheco, M. Melissa, additional, Vargas-Arispuro, Irasema, additional, González-Aguilar, Gustavo A., additional, Martínez-Téllez, Miguel A., additional, and Ayala-Zavala, J. Fernando, additional
Published: 2020
Full Text: View/download PDF

120. A Subcutaneous Implant of Tenofovir Alafenamide Fumarate Causes Local Inflammation and Tissue Necrosis in Rabbits and Macaques

Author: Su, Jonathan T., primary, Simpson, Solange M., additional, Sung, Samuel, additional, Tfaily, Ewa Bryndza, additional, Veazey, Ronald, additional, Marzinke, Mark, additional, Qiu, Jiang, additional, Watrous, David, additional, Widanapathirana, Lakmini, additional, Pearson, Elizabeth, additional, Peet, M. Melissa, additional, Karunakaran, Dipu, additional, Grasperge, Brooke, additional, Dobek, Georgina, additional, Cain, Charlette M., additional, Hope, Thomas, additional, and Kiser, Patrick F., additional
Published: 2020
Full Text: View/download PDF

121. Synergistic mode of action of catechin, vanillic and protocatechuic acids to inhibit the adhesion of uropathogenic Escherichia coli on silicone surfaces

Author: Bernal-Mercado, A.T., primary, Gutierrez-Pacheco, M. Melissa, additional, Encinas-Basurto, D., additional, Mata-Haro, V., additional, Lopez-Zavala, A.A., additional, Islas-Osuna, M.A., additional, Gonzalez-Aguilar, G.A., additional, and Ayala-Zavala, J.F., additional
Published: 2020
Full Text: View/download PDF

122. Expression of Emotion in Body and Face

Author: Crane, Elizabeth A., primary, Gross, M. Melissa, additional, and Fredrickson, Barbara L., additional
Published: 2006
Full Text: View/download PDF

123. Pasture diversification to combat climate change impacts on grazing dairy production

Author: M. Melissa Rojas-Downing, Sabah Anwer Dawood Al Masraf, Mohammad Abouali, A. Pouyan Nejadhashemi, Fariborz Daneshvar, Timothy M. Harrigan, Matthew R. Herman, and Zhen Zhang
Subjects: Global and Planetary Change, geography, geography.geographical_feature_category, 010504 meteorology & atmospheric sciences, Ecology, biology, business.industry, Agroforestry, 0208 environmental biotechnology, Climate change, 02 engineering and technology, Lolium multiflorum, biology.organism_classification, 01 natural sciences, Pasture, 020801 environmental engineering, Red Clover, Dactylis glomerata, Agronomy, Grazing, Trifolium repens, Environmental science, Livestock, business, 0105 earth and related environmental sciences
Abstract: Among livestock systems, grazing is likely to be most impacted by climate change because of its dependency to feed quality and availability. In order to reduce the impact of climate change on grazing livestock systems, adaptation measures should be implemented. The goal of this study is to identify the best pasture composition for a representative grazing dairy farm in Michigan in order to reduce the impacts of climate change on production. In order to achieve the goal of this study, three objectives were sought: (1) identify the best pasture composition, (2) assess economic and resource use impacts of pasture compositions under future climate scenarios, and (3) evaluate the resiliency of pasture compositions. A representative farm was developed based on a livestock practices survey and incorporated into the Integrated Farm System Model (IFSM). For the pasture compositions, four cool-season grass species and two legumes were evaluated under both current and future climate scenarios. The effectiveness of adaptation measures based on economic and resource use criteria was evaluated. Overall, the pasture composition with 50% perennial ryegrass (Lolium multiflorum) and 50% red clover (Trifolium pratense) was identified as the best. In addition, the increase in precipitation and temperature of the most intensive climate scenario could significantly improve farm net return per cow (Bos taurus) and whole farm profit while no significant impact was observed on resource use criteria. Finally, the overall sensitivity assessment showed that the most resilient pasture composition under future climate scenarios was ryegrass with red clover and the least resilient was orchardgrass (Dactylis glomerata) with white clover (Trifolium repens).
Published: 2017

124. Vehicle Emissions as an Important Urban Ammonia Source in the United States and China

Author: Lei Tao, Robert J. Griffin, H. W. Wallace, Levi M. Golston, Denise L. Mauzerall, M. Melissa Yang, Da Pan, Mark A. Zondlo, Yan Zhang, David J. Miller, Tong Zhu, Y. J. Leong, and Kang Sun
Subjects: China, 010504 meteorology & atmospheric sciences, Population, 010501 environmental sciences, Atmospheric sciences, 01 natural sciences, Ammonia, chemistry.chemical_compound, Mobile laboratory, Beijing, Environmental Chemistry, Cities, Emission inventory, education, Air quality index, Vehicle Emissions, 0105 earth and related environmental sciences, Aerosols, Air Pollutants, education.field_of_study, Environmental engineering, General Chemistry, United States, chemistry, Environmental science, Environmental Monitoring
Abstract: Ammoniated aerosols are important for urban air quality, but emissions of the key precursor NH3 are not well quantified. Mobile laboratory observations are used to characterize fleet-integrated NH3 emissions in six cities in the U.S. and China. Vehicle NH3:CO2 emission ratios in the U.S. are similar between cities (0.33–0.40 ppbv/ppmv, 15% uncertainty) despite differences in fleet composition, climate, and fuel composition. While Beijing, China has a comparable emission ratio (0.36 ppbv/ppmv) to the U.S. cities, less developed Chinese cities show higher emission ratios (0.44 and 0.55 ppbv/ppmv). If the vehicle CO2 inventories are accurate, NH3 emissions from U.S. vehicles (0.26 ± 0.07 Tg/yr) are more than twice those of the National Emission Inventory (0.12 Tg/yr), while Chinese NH3 vehicle emissions (0.09 ± 0.02 Tg/yr) are similar to a bottom-up inventory. Vehicle NH3 emissions are greater than agricultural emissions in counties containing near half of the U.S. population and require reconsideration in u...
Published: 2017

125. Climate change and livestock: Impacts, adaptation, and mitigation

Author: A. Pouyan Nejadhashemi, Timothy M. Harrigan, Sean A. Woznicki, and M. Melissa Rojas-Downing
Subjects: Atmospheric Science, Livestock, Mitigation, 010504 meteorology & atmospheric sciences, Natural resource economics, Geography, Planning and Development, Climate change, lcsh:QC851-999, Management, Monitoring, Policy and Law, Standard of living, Greenhouse gas, 01 natural sciences, Heat stress, Crop, Production (economics), Adaptation, 0105 earth and related environmental sciences, Global and Planetary Change, Food security, business.industry, Agroforestry, 0402 animal and dairy science, 04 agricultural and veterinary sciences, 040201 dairy & animal science, Agriculture, lcsh:Meteorology. Climatology, business
Abstract: Global demand for livestock products is expected to double by 2050, mainly due to improvement in the worldwide standard of living. Meanwhile, climate change is a threat to livestock production because of the impact on quality of feed crop and forage, water availability, animal and milk production, livestock diseases, animal reproduction, and biodiversity. This study reviews the global impacts of climate change on livestock production, the contribution of livestock production to climate change, and specific climate change adaptation and mitigation strategies in the livestock sector. Livestock production will be limited by climate variability as animal water consumption is expected to increase by a factor of three, demand for agricultural lands increase due to need for 70% growth in production, and food security concern since about one-third of the global cereal harvest is used for livestock feed. Meanwhile, the livestock sector contributes 14.5% of global greenhouse gas (GHG) emissions, driving further climate change. Consequently, the livestock sector will be a key player in the mitigation of GHG emissions and improving global food security. Therefore, in the transition to sustainable livestock production, there is a need for: a) assessments related to the use of adaptation and mitigation measures tailored to the location and livestock production system in use, and b) policies that support and facilitate the implementation of climate change adaptation and mitigation measures.
Published: 2017

126. BEYOND BINARIES OF DISABILITY IN WRITING CENTER STUDIES.

Author: Elston, M. Melissa, Green, Nicole, and Hubrig, Ada/Adam
Subjects: WRITING centers, DISABILITIES, PRAXIS (Process), COLLEGE buildings
Published: 2022

127. Expression of Emotion in Body and Face.

Author: Elizabeth A. Crane, M. Melissa Gross, and Barbara L. Fredrickson
Published: 2006
Full Text: View/download PDF

128. Expression of Emotion in Body and Face

Author: Crane, Elizabeth A., Gross, M. Melissa, Fredrickson, Barbara L., Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Carbonell, Jaime G., editor, Siekmann, Jörg, editor, Gratch, Jonathan, editor, Young, Michael, editor, Aylett, Ruth, editor, Ballin, Daniel, editor, and Olivier, Patrick, editor
Published: 2006
Full Text: View/download PDF

129. A Subcutaneous Implant of Tenofovir Alafenamide Fumarate Causes Local Inflammation and Tissue Necrosis in Rabbits and Macaques

Author: David Watrous, Jonathan T. Su, Mark A. Marzinke, Dipu Karunakaran, Georgina L Dobek, M. Melissa Peet, Ewa Bryndza Tfaily, Elizabeth Pearson, Jiang Qiu, Lakmini Widanapathirana, Ronald S. Veazey, Brooke Grasperge, Samuel Sung, Thomas J. Hope, Patrick F. Kiser, Solange M. Simpson, and Charlette M. Cain
Subjects: Male, Pathology, Necrosis, implant, Polyurethanes, preexposure prophylaxis, HIV Infections, 02 engineering and technology, New Zealand white rabbit, Subcutaneous Tissue, Fumarates, Medicine, Pharmacology (medical), Drug Implants, 0303 health sciences, Alanine, biology, 021001 nanoscience & nanotechnology, antiretroviral agents, 3. Good health, Infectious Diseases, histopathology, Female, Rabbits, medicine.symptom, 0210 nano-technology, medicine.medical_specialty, Anti-HIV Agents, Inflammation, Peripheral blood mononuclear cell, Tenofovir alafenamide, Antiviral Agents, 03 medical and health sciences, Pharmacokinetics, In vivo, Animals, Humans, Tenofovir, 030304 developmental biology, Pharmacology, 030306 microbiology, business.industry, Adenine, biology.organism_classification, Macaca mulatta, Delayed-Action Preparations, Histopathology, Implant, business
Abstract: We describe the in vitro and in vivo evaluation of a subcutaneous reservoir implant delivering tenofovir alafenamide hemifumarate (TAF) for the prevention of HIV infection. These long-acting reservoir implants were able to deliver antiretroviral drug for over 90 days in vitro and in vivo. We evaluated the implants for implantation site histopathology and pharmacokinetics in plasma and tissues for up to 12 weeks in New Zealand White rabbit and rhesus macaque models., We describe the in vitro and in vivo evaluation of a subcutaneous reservoir implant delivering tenofovir alafenamide hemifumarate (TAF) for the prevention of HIV infection. These long-acting reservoir implants were able to deliver antiretroviral drug for over 90 days in vitro and in vivo. We evaluated the implants for implantation site histopathology and pharmacokinetics in plasma and tissues for up to 12 weeks in New Zealand White rabbit and rhesus macaque models. A dose-ranging study in rabbits demonstrated dose-dependent pharmacokinetics and local inflammation up to severe necrosis around the active implants. The matched placebos showed normal wound healing and fibrous tissue encapsulation of the implant. We designed a second implant with a lower release rate and flux of TAF and achieved a median cellular level of tenofovir diphosphate of 42 fmol per 106 rhesus macaque peripheral blood mononuclear cells at a TAF dose of 10 μg/kg/day. This dose and flux of TAF also resulted in adverse local inflammation and necrosis near the implant in rhesus macaques. The level of inflammation in the primates was markedly lower in the placebo group than in the active-implant group. The histological inflammatory response to the TAF implant at 4 and 12 weeks in primates was graded as a severe reaction. Thus, while we were able to achieve a sustained target dose, we observed an unacceptable inflammatory response locally at the implant tissue interface.
Published: 2019

130. Homologous recombination DNA repair defects in PALB2-associated breast cancers

Author: Li, A. (Anqi), Geyer, F. C. (Felipe C.), Blecua, P. (Pedro), Lee, J. Y. (Ju Youn), Selenica, P. (Pier), Brown, D. N. (David N.), Pareja, F. (Fresia), Lee, S. S. (Simon S. K.), Kumar, R. (Rahul), Rivera, B. (Barbara), Bi, R. (Rui), Piscuoglio, S. (Salvatore), Wen, H. Y. (Hannah Y.), Lozada, J. R. (John R.), Gularte-Merida, R. (Rodrigo), Cavallone, L. (Luca), Rezoug, Z. (Zoulikha), Nguyen-Dumont, T. (Tu), Peterlongo, P. (Paolo), Tondini, C. (Carlo), Terkelsen, T. (Thorkild), Ronlund, K. (Karina), Boonen, S. E. (Susanne E.), Mannerma, A. (Arto), Winqvist, R. (Robert), Janatova, M. (Marketa), Rajadurai, P. (Pathmanathan), Xia, B. (Bing), Norton, L. (Larry), Robson, M. E. (Mark E.), Ng, P.-S. (Pei-Sze), Looi, L.-M. (Lai-Meng), Southey, M. C. (Melissa C.), Weigelt, B. (Britta), Soo-Hwang, T. (Teo), Tischkowitz, M. (Marc), Foulkes, W. D. (William D.), Reis-Filho, J. S. (Jorge S.), Aghmesheh, M. (Morteza), Amor, D. (David), Andrews, L. (Leslie), Antill, Y. (Yoland), Balleine, R. (Rosemary), Beesley, J. (Jonathan), Blackburn, A. (Anneke), Bogwitz, M. (Michael), Brown, M. (Melissa), Burgess, M. (Matthew), Burke, J. (Jo), Butow, P. (Phyllis), Caldon, L. (Liz), Campbell, I. (Ian), Christian, A. (Alice), Clarke, C. (Christine), Cohen, P. (Paul), Crook, A. (Ashley), Cui, J. (James), Cummings, M. (Margaret), Dawson, S.-J. (Sarah-Jane), De Fazio, A. (Anna), Delatycki, M. (Martin), Dobrovic, A. (Alex), Dudding, T. (Tracy), Duijf, P. (Pascal), Edkins, E. (Edward), Edwards, S. (Stacey), Farshid, G. (Gelareh), Fellows, A. (Andrew), Field, M. (Michael), Flanagan, J. (James), Fong, P. (Peter), Forbes, J. (John), Forrest, L. (Laura), Fox, S. (Stephen), French, J. (Juliet), Friedlander, M. (Michael), Ortega, D. G. (David Gallego), Gattas, M. (Michael), Giles, G. (Graham), Gill, G. (Grantley), Gleeson, M. (Margaret), Greening, S. (Sian), Haan, E. (Eric), Harris, M. (Marion), Hayward, N. (Nick), Hickie, I. (Ian), Hopper, J. (John), Hunt, C. (Clare), James, P. (Paul), Jenkins, M. (Mark), Kefford, R. (Rick), Kentwell, M. (Maira), Kirk, J. (Judy), Kollias, J. (James), Lakhani, S. (Sunil), Lindeman, G. (Geoff), Lipton, L. (Lara), Lobb, L. (Lizz), Lok, S. (Sheau), Macrea, F. (Finlay), Mane, G. (Graham), Marsh, D. (Deb), Mclachlan, S.-A. (Sue-Anne), Meiser, B. (Bettina), Milne, R. (Roger), Nightingale, S. (Sophie), O'Connell, S. (Shona), Pachter, N. (Nick), Patterson, B. (Briony), Phillips, K. (Kelly), Saleh, M. (Mona), Salisbury, E. (Elizabeth), Saunders, C. (Christobel), Saunus, J. (Jodi), Scott, C. (Clare), Scott, R. (Rodney), Sexton, A. (Adrienne), Shelling, A. (Andrew), Simpson, P. (Peter), Spigelman, A. (Allan), Spurdle, M. (Mandy), Stone, J. (Jennifer), Taylor, J. (Jessica), Thorne, H. (Heather), Trainer, A. (Alison), Trench, G. (Georgia), Tucker, K. (Kathy), Visvader, J. (Jane), Walker, L. (Logan), Wallis, M. (Mathew), Williams, R. (Rachael), Winship, I. (Ingrid), Wu, K. (Kathy), Young, M. A. (Mary Anne), Li, Anqi, Geyer, Felipe C, Blecua, Pedro, Lee, Ju Youn, Duijf, Pascal, Reis-Filho, Jorge S, Li, Anqi [0000-0003-1409-1858], Kumar, Rahul [0000-0002-6927-5390], Rivera, Barbara [0000-0001-9434-6288], Piscuoglio, Salvatore [0000-0003-2686-2939], Lozada, John R. [0000-0001-8953-4110], Gularte-Mérida, Rodrigo [0000-0002-4383-2523], Peterlongo, Paolo [0000-0001-6951-6855], Robson, Mark E. [0000-0002-3109-1692], Looi, Lai-Meng [0000-0001-8325-0117], Foulkes, William D. [0000-0001-7427-4651], Apollo - University of Cambridge Repository, Lozada, John R [0000-0001-8953-4110], Robson, Mark E [0000-0002-3109-1692], and Foulkes, William D [0000-0001-7427-4651]
Subjects: 0301 basic medicine, IMPACT, DNA repair, PALB2, gene frequency, lcsh:RC254-282, RECOMMENDATIONS, Germline, Article, Loss of heterozygosity, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, breast cancer, Breast cancer, 631/67/68, MUTATIONAL PROCESSES, Cancer genomics, Medicine, Pharmacology (medical), Radiology, Nuclear Medicine and imaging, Allele, AMERICAN SOCIETY, Cancer genetics, Genetics, Science & Technology, Massive parallel sequencing, LANDSCAPE, business.industry, 631/67/1347, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 692/699/67/69, BRCA2, GENE, 3. Good health, 030104 developmental biology, Oncology, gene inactivation, 030220 oncology & carcinogenesis, kConFab Investigators, Homologous recombination, business, Life Sciences & Biomedicine, CLINICAL ONCOLOGY/COLLEGE
Abstract: Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD.
Published: 2019

131. Topical Inserts: A Versatile Delivery Form for HIV Prevention

Author: Andrea R. Thurman, Meredith R. Clark, M. Melissa Peet, Vivek Agrahari, Homaira Hanif, Gustavo F. Doncel, Onkar N. Singh, and Sharon Anderson
Subjects: medicine.medical_specialty, Human immunodeficiency virus (HIV), Pharmaceutical Science, lcsh:RS1-441, 02 engineering and technology, Review, medicine.disease_cause, Dosage form, lcsh:Pharmacy and materia medica, on-demand, 03 medical and health sciences, 0302 clinical medicine, Rectal mucosa, fast-disintegrating, medicine, 030212 general & internal medicine, Intensive care medicine, Sti prevention, extended-release, Potential impact, business.industry, tablets, HIV, 021001 nanoscience & nanotechnology, protection, Microbicides for sexually transmitted diseases, microbicides, Rectal administration, Drug delivery, rectal drug delivery, 0210 nano-technology, business, vaginal drug delivery
Abstract: The development of topical inserts for the prevention of sexually transmitted infections (STIs), particularly human immunodeficiency virus (HIV), represents a promising alternative to oral and parenteral pre-exposure prophylaxis (PrEP) dosage forms. They may be used for vaginal and/or rectal administration of a variety of agents with antiviral activity. Topical inserts deliver drugs to the portal of viral entry, i.e., the genital or rectal mucosa, with low systemic exposure, and therefore are safer and have fewer side effects than systemic PrEP agents. They may dissolve fast, releasing the active drugs within minutes of insertion, or slowly for long-acting drug delivery. Furthermore, they are user-friendly being easy to administer, discreet and highly portable. They are also economical and easy to manufacture at scale and to distribute, with excellent stability and shelf-life. Altogether, topical inserts represent a particularly promising form of drug delivery for HIV and STI prevention. Highlighted within this review are end-user acceptability research dedicated to understanding preferred attributes for this form of drug delivery, advantages and disadvantages of the formulation platform options, considerations for their development, clinical assessment of select placebo prototypes, future directions, and the potential impact of this dosage form on the HIV prevention landscape.
Published: 2019

132. Folliculotropic mycosis fungoides presents with two distinct clinicopathological presentations: an international virtual study

Author: Paul Haun, Emmanuella Guenova-Hötzenecker, John A. Zic, José Antonio Sanches, Maxime Battistella, Joan Guitart, Christina Mitteldorf, Carlos A. Torres-Cabala, Antonio Subtil, Lia Papadavid, Helmut Beltraminelli, M. Melissa Pulitzer, Larisa J. Geskin, Pietro Quaglino, Youn H. Kim, Emmilia Hodak, Julia Scarisbrick, Christiane Querfeld, Madeleine Duvic, Werner Kempf, Pablo Ortiz, Jacqueline M. Junkins-Hopkins, Martine Bagot, Antonio Cozzio, Rudolf Stadler, Alistair Robson, Alejandro A. Gru, Bethanie Rooke, and Robert Knobler
Subjects: Cancer Research, medicine.medical_specialty, Oncology, business.industry, Medicine, business, Folliculotropic Mycosis Fungoides, Dermatology
Published: 2019

133. Genetic architecture of human plasma lipidome and its link to cardiovascular disease

Author: Tabassum, R. (Rubina), Ramo, J. T. (Joel T.), Ripatti, P. (Pietari), Koskela, J. T. (Jukka T.), Kurki, M. (Mitja), Karjalainen, J. (Juha), Palta, P. (Priit), Hassan, S. (Shabbeer), Nunez-Fontarnau, J. (Javier), Kiiskinen, T. T. (Tuomo T. J.), Soderlund, S. (Sanni), Matikainen, N. (Niina), Gerl, M. J. (Mathias J.), Surma, M. A. (Michal A.), Klose, C. (Christian), Stitziel, N. O. (Nathan O.), Laivuori, H. (Hannele), Havulinna, A. S. (Aki S.), Service, S. K. (Susan K.), Salomaa, V. (Veikko), Pirinen, M. (Matti), Jauhiainen, M. (Matti), Daly, M. J. (Mark J.), Freimer, N. B. (Nelson B.), Palotie, A. (Aarno), Taskinen, M.-R. (Marja-Riitta), Simons, K. (Kai), Ripatti, S. (Samuli), Jalanko, A. (Anu), Kaprio, J. (Jaakko), Donner, K. (Kati), Kaunisto, M. (Mari), Mars, N. (Nina), Dada, A. (Alexander), Shcherban, A. (Anastasia), Ganna, A. (Andrea), Lehisto, A. (Arto), Kilpelainen, E. (Elina), Brein, G. (Georg), Awaisa, G. (Ghazal), Harju, J. (Jarmo), Parr, K. (Kalle), Parolo, P. D. (Pietro Della Briotta), Kajanne, R. (Risto), Lemmela, S. (Susanna), Sipila, T. P. (Timo P.), Sipila, T. (Tuomas), Lyhs, U. (Ulrike), Llorens, V. (Vincent), Niiranen, T. (Teemu), Kristiansson, K. (Kati), Mannikko, L. (Lotta), Jimenez, M. G. (Manuel Gonzalez), Perola, M. (Markus), Wong, R. (Regis), Kilpi, T. (Terhi), Hiekkalinna, T. (Tero), Jarvensivu, E. (Elina), Kaiharju, E. (Essi), Mattsson, H. (Hannele), Laukkanen, M. (Markku), Laiho, P. (Paivi), Lahteenmaki, S. (Sini), Sistonen, T. (Tuuli), Soini, S. (Sirpa), Ziemann, A. (Adam), Lehtonen, A. (Anne), Lertratanakul, A. (Apinya), Georgantas, B. (Bob), Riley-Gillis, B. (Bridget), Quarless, D. (Danjuma), Rahimov, F. (Fedik), Heap, G. (Graham), Jacob, H. (Howard), Waring, J. (Jeffrey), Davis, J. W. (Justin Wade), Smaoui, N. (Nizar), Popovic, R. (Relja), Esmaeeli, S. (Sahar), Waring, J. (Jeff), Matakidou, A. (Athena), Challis, B. (Ben), Close, D. (David), Petrovski, S. (Slave), Karlsson, A. (Antti), Schleutker, J. (Johanna), Pulkki, K. (Kari), Virolainen, P. (Petri), Kallio, L. (Lila), Mannermaa, A. (Arto), Heikkinen, S. (Sami), Kosma, V.-M. (Veli-Matti), Chen, C.-Y. (Chia-Yen), Runz, H. (Heiko), Liu, J. (Jimmy), Bronson, P. (Paola), John, S. (Sally), Landenpera, S. (Sanni), Eaton, S. (Susan), Zhou, W. (Wei), Hendolin, M. (Minna), Tuovila, O. (Outi), Pakkanen, R. (Raimo), Maranville, J. (Joseph), Usiskin, K. (Keith), Hochfeld, M. (Marla), Plenge, R. (Robert), Yang, R. (Robert), Biswas, S. (Shameek), Greenberg, S. (Steven), Laakkonen, E. (Eija), Kononen, J. (Juha), Paloneva, J. (Juha), Kujala, U. (Urho), Kuopio, T. (Teijo), Laukkanen, J. (Jari), Kangasniemi, E. (Eeva), Savinainen, K. (Kimmo), Laaksonen, R. (Reijo), Arvas, M. (Mikko), Ritari, J. (Jarmo), Partanen, J. (Jukka), Hyvarinen, K. (Kati), Wahlfors, T. (Tiina), Peterson, A. (Andrew), Oh, D. (Danny), Chang, D. (Diana), Teng, E. (Edmond), Strauss, E. (Erich), Kerchner, G. (Geoff), Chen, H. (Hao), Chen, H. (Hubert), Schutzman, J. (Jennifer), Michon, J. (John), Hunkapiller, J. (Julie), McCarthy, M. (Mark), Bowers, N. (Natalie), Lu, T. (Tim), Bhangale, T. (Tushar), Pulford, D. (David), Waterworth, D. (Dawn), Kulkarni, D. (Diptee), Xu, F. (Fanli), Betts, J. (Jo), Gordillo, J. E. (Jorge Esparza), Hoffman, J. (Joshua), Auro, K. (Kirsi), McCarthy, L. (Linda), Ghosh, S. (Soumitra), Ehm, M. (Meg), Pitkanen, K. (Kimmo), Makela, T. (Tomi), Loukola, A. (Anu), Joensuu, H. (Heikki), Sinisalo, J. (Juha), Eklund, K. (Kari), Aaltonen, L. (Lauri), Farkkila, M. (Martti), Carpen, O. (Olli), Kauppi, P. (Paula), Tienari, P. (Pentti), Ollila, T. (Terhi), Tuomi, T. (Tiinamaija), Meretoja, T. (Tuomo), Pitkaranta, A. (Anne), Turunen, J. (Joni), Hannula-Jouppi, K. (Katariina), Pikkarainen, S. (Sampsa), Seitsonen, S. (Sanna), Koskinen, M. (Miika), Palomaki, A. (Antti), Rinne, J. (Juha), Metsarinne, K. (Kaj), Elenius, K. (Klaus), Pirila, L. (Laura), Koulu, L. (Leena), Voutilainen, M. (Markku), Juonala, M. (Markus), Peltonen, S. (Sirkku), Aaltonen, V. (Vesa), Loboda, A. (Andrey), Podgornaia, A. (Anna), Chhibber, A. (Aparna), Chu, A. (Audrey), Fox, C. (Caroline), Diogo, D. (Dorothee), Holzinger, E. (Emily), Eicher, J. (John), Gormley, P. (Padhraig), Mehta, V. (Vinay), Wang, X. (Xulong), Kettunen, J. (Johannes), Pylkas, K. (Katri), Kalaoja, M. (Marita), Karjalainen, M. (Minna), Hinttala, R. (Reetta), Kaarteenaho, R. (Riitta), Vainio, S. (Seppo), Mantere, T. (Tuomo), Remes, A. (Anne), Huhtakangas, J. (Johanna), Junttila, J. (Juhani), Tasanen, K. (Kaisa), Huilaja, L. (Laura), Luodonpaa, M. (Marja), Hautala, N. (Nina), Karihtala, P. (Peeter), Kauppila, S. (Saila), Harju, T. (Terttu), Blomster, T. (Timo), Soininen, H. (Hilkka), Harvima, I. (Ilkka), Pihlajamaki, J. (Jussi), Kaarniranta, K. (Kai), Pelkonen, M. (Margit), Laakso, M. (Markku), Hiltunen, M. (Mikko), Kiviniemi, M. (Mikko), Kaipiainen-Seppanen, O. (Oili), Auvinen, P. (Paivi), Kalviainen, R. (Reetta), Julkunen, V. (Valtteri), Malarstig, A. (Anders), Hedman, A. (Asa), Marshal, C. (Catherine), Whelan, C. (Christopher), Lehtonen, H. (Heli), Parkkinen, J. (Jaakko), Linden, K. (Kari), Kalpala, K. (Kirsi), Miller, M. (Melissa), Bing, N. (Nan), McDonough, S. (Stefan), Chen, X. (Xing), Hu, X. (Xinli), Wu, Y. (Ying), Auranen, A. (Annika), Jussila, A. (Airi), Uusitalo-Jarvinen, H. (Hannele), Kankaanranta, H. (Hannu), Uusitalo, H. (Hannu), Peltola, J. (Jukka), Kahonen, M. (Mika), Isomaki, P. (Pia), Laitinen, T. (Tarja), Salmi, T. (Teea), Muslin, A. (Anthony), Wang, C. (Clarence), Chatelain, C. (Clement), Xu, E. (Ethan), Auge, F. (Franck), Call, K. (Kathy), Klinger, K. (Kathy), Crohns, M. (Marika), Gossel, M. (Matthias), Palin, K. (Kimmo), Rivas, M. (Manuel), Siirtola, H. (Harri), and Tabuenca, J. G. (Javier Gracia)
Subjects: lipids (amino acids, peptides, and proteins)
Abstract: Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P
Published: 2019

134. Early probiotic supplementation and the risk of celiac disease in children at genetic risk

Author: Uusitalo, U. (Ulla), Aronsson, C. A. (Carin Andren), Liu, X. (Xiang), Kurppa, K. (Kalle), Yang, J. (Jimin), Liu, E. (Edwin), Skidmore, J. (Jennifer), Winkler, C. (Christiane), Rewers, M. J. (Marian J.), Hagopian, W. A. (William A.), She, J.-X. (Jin-Xiong), Toppari, J. (Jorma), Ziegler, A.-G. (Anette-G), Akolkar, B. (Beena), Norris, J. M. (Jill M.), Virtanen, S. M. (Suvi M.), Krischer, J. P. (Jeffrey P.), Agardh, D. (Daniel), Rewers, M. (Marian), Bautista, K. (Kimberly), Baxter, J. (Judith), Felipe-Morales, D. (Daniel), Driscoll, K. (Kimberly), Frohnert, B. I. (Brigitte, I), Gallant, M. (Marisa), Gesualdo, P. (Patricia), Hoffman, M. (Michelle), Karban, R. (Rachel), Norris, J. (Jill), Steck, A. (Andrea), Waugh, K. (Kathleen), Simell, O. G. (Olli G.), Adamsson, A. (Annika), Ahonen, S. (Suvi), Akerlund, M. (Mari), Hekkala, A. (Anne), Holappa, H. (Henna), Hyoty, H. (Heikki), Ikonen, A. (Anni), Ilonen, J. (Jorma), Jaminki, S. (Sinikka), Jokipuu, S. (Sanna), Karlsson, L. (Leena), Kahonen, M. (Miia), Knip, M. (Mikael), Koivikko, M.-L. (Minna-Liisa), Koreasalo, M. (Mirva), Kytola, J. (Jarita), Latva-aho, T. (Tiina), Lindfors, K. (Katri), Lonnrot, M. (Maria), Mantymaki, E. (Elina), Mattila, M. (Markus), Multasuo, K. (Katja), Mykkanenv, T. (Teija), Niininen, T. (Titha), Niinisto, S. (Sari), Nyblom, M. (Mia), Oikarinen, S. (Sami), Ollikainen, P. (Paula), Pohjola, S. (Sirpa), Rajala, P. (Petra), Rautanen, J. (Jenna), Riikonen, A. (Anne), Romo, M. (Minna), Ruohonen, S. (Suvi), Simell, S. (Satu), Sjoberg, M. (Maija), Stenius, A. (Aino), Tossavainen, P. (Paivi), Vaha-Makila, M. (Mari), Vainionpaa, S. (Sini), Varjonen, E. (Eeva), Veijola, R. (Riitta), Viinikangas, I. (Irene), Schatz, D. (Desmond), Hopkins, D. (Diane), Steed, L. (Leigh), Bryant, J. (Jennifer), Silvis, K. (Katherine), Haller, M. (Michael), Gardiner, M. (Melissa), Mclndoe, R. (Richard), Sharma, A. (Ashok), Anderson, S. W. (Stephen W.), Jacobsen, L. (Laura), Marks, J. (John), Towe, P. D. (P. D.), Ziegler, A. G. (Anette G.), Bonifacio, E. (Ezio), D'Angelo, M. (Miryam), Gavrisan, A. (Anita), Gezginci, C. (Cigdem), Heublein, A. (Anja), Hoffmann, V. (Verena), Hummel, S. (Sandra), Keimer, A. (Andrea), Knopff, A. (Annette), Koch, C. (Charlotte), Koletzko, S. (Sibylle), Ramminger, C. (Claudia), Roth, R. (Roswith), Scholz, M. (Marlon), Stock, J. (Joanna), Warncke, K. (Katharina), Wendel, L. (Lorena), Lernmark, A. (Ake), Ask, M. (Maria), Bremer, J. (Jenny), Cilio, C. (Corrado), Ericson-Hallstrom, E. (Emelie), Fors, A. (Annika), Fransson, L. (Lina), Gard, T. (Thomas), Bennet, R. (Rasmus), Hansen, M. (Monika), Hyberg, S. (Susanne), Jisser, H. (Hanna), Johansen, F. (Fredrik), Jonsdottir, B. (Berglind), Jovic, S. (Silvija), Larsson, H. E. (Helena Elding), Lindstrom, M. (Marielle), Lundgren, M. (Markus), Manson-Martinez, M. (Maria), Markan, M. (Maria), Melin, J. (Jessica), Mestan, Z. (Zeliha), Nilsson, C. (Caroline), Ottosson, K. (Karin), Rahmati, K. (Kobra), Ramelius, A. (Anita), Salami, F. (Falastin), Sjoberg, A. (Anette), Sjoberg, B. (Birgitta), Torn, C. (Carina), Wallin, A. (Anne), Wimar, A. (Asa), Aberg, S. (Sofie), Killian, M. (Michael), Crouch, C. C. (Claire Cowen), Akramoff, A. (Ashley), Chavoshi, M. (Masumeh), Dunson, K. (Kayleen), Hervey, R. (Rachel), Lyons, R. (Rachel), Meyer, A. (Arlene), Mulenga, D. (Denise), Radtke, J. (Jared), Romancik, M. (Matei), Schmitt, D. (Davey), Schwabe, J. (Julie), Zink, S. (Sarah), Becker, D. (Dorothy), Franciscus, M. (Margaret), Smith, M. D. (Maryellen Dalmagro-Elias), Daftary, A. (Ashi), Klein, M. B. (Mary Beth), Yates, C. (Chrystal), Austin-Gonzalez, S. (Sarah), Avendano, M. (Maryouri), Baethke, S. (Sandra), Brown, R. (Rasheedah), Burkhardt, B. (Brant), Butterworth, M. (Martha), Clasen, J. (Joanna), Cuthbertson, D. (David), Eberhard, C. (Christopher), Fiske, S. (Steven), Garmeson, J. (Jennifer), Gowda, V. (Veena), Heyman, K. (Kathleen), Hsiao, B. (Belinda), Karges, C. (Christina), Laras, F. P. (Francisco Perez), Lee, H.-S. (Hye-Seung), Li, Q. (Qian), Liu, S. (Shu), Lynch, K. (Kristian), Maguire, C. (Colleen), Malloy, J. (Jamie), McCarthy, C. (Cristina), Merrell, A. (Aubrie), Meulemans, S. (Steven), Parikh, H. (Hemang), Quigley, R. (Ryan), Remedios, C. (Cassandra), Shaffer, C. (Chris), Smith, L. (Laura), Smith, S. (Susan), Sulman, N. (Noah), Tamura, R. (Roy), Tewey, D. (Dena), Toth, M. (Michael), Vehik, K. (Kendra), Vijayakandipan, P. (Ponni), Wood, K. (Keith), Abbondondolo, M. (Michael), Ballard, L. (Lori), Hadley, D. (David), McLeod, W. (Wendy), Yu, L. (Liping), Miao, D. (Dongmei), Bingley, P. (Polly), Williams, A. (Alistair), Chandler, K. (Kyla), Ball, O. (Olivia), Kelland, I. (Ilana), Grace, S. (Sian), Hagopian, W. (William), Erlich, H. (Henry), Mack, S. J. (Steven J.), Fear, A. L. (Anna Lisa), Ke, S. (Sandra), Mulholland, N. (Niveen), Bourcier, K. (Kasia), Briese, T. (Thomas), Johnson, S. B. (Suzanne Bennett), and Triplett, E. (Eric)
Subjects: dietary supplements, probiotics, infant formula, celiac disease, celiac disease autoimmunity
Abstract: Probiotics are linked to positive regulatory effects on the immune system. The aim of the study was to examine the association between the exposure of probiotics via dietary supplements or via infant formula by the age of 1 year and the development of celiac disease autoimmunity (CDA) and celiac disease among a cohort of 6520 genetically susceptible children. Use of probiotics during the first year of life was reported by 1460 children. Time-to-event analysis was used to examine the associations. Overall exposure of probiotics during the first year of life was not associated with either CDA (n = 1212) (HR 1.15; 95%CI 0.99, 1.35; p = 0.07) or celiac disease (n = 455) (HR 1.11; 95%CI 0.86, 1.43; p = 0.43) when adjusting for known risk factors. Intake of probiotic dietary supplements, however, was associated with a slightly increased risk of CDA (HR 1.18; 95%CI 1.00, 1.40; p = 0.043) compared to children who did not get probiotics. It was concluded that the overall exposure of probiotics during the first year of life was not associated with CDA or celiac disease in children at genetic risk.
Published: 2019

135. Fitness Level And Vertical Forces Generated During Walking In Post-menopausal Women: 816 Board #38 10:30 AM – 12:00 PM

Author: Fogleman, Katrina M., Gross, M. Melissa, and Borer, Katarina T.
Published: 2005

136. Neurodevelopmental delay: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data

Author: Villagomez, A.N. (Adrienne N.), Muñoz, F.M. (Flor M.), Peterson, R.L. (Robin L.), Colbert, A.M. (Alison M.), Gladstone, M. (Melissa), MacDonald, B. (Beatriz), Wilson, R. (Rebecca), Fairlie, L. (Lee), Gerner, G.J. (Gwendolyn J.), Patterson, J. (Jackie), Boghossian, N.S. (Nansi S.), Burton, V.J. (Vera Joanna), Cortés, M. (Margarita), Katikaneni, L.D. (Lakshmi D.), Larson, J.C.G. (Jennifer C.G.), Angulo, A.S. (Abigail S.), Joshi, J. (Jyoti), Nesin, M. (Mirjana), Padula, M.A. (Michael A.), Kochhar, S. (Sonali), Connery, A.K. (Amy K.), Villagomez, A.N. (Adrienne N.), Muñoz, F.M. (Flor M.), Peterson, R.L. (Robin L.), Colbert, A.M. (Alison M.), Gladstone, M. (Melissa), MacDonald, B. (Beatriz), Wilson, R. (Rebecca), Fairlie, L. (Lee), Gerner, G.J. (Gwendolyn J.), Patterson, J. (Jackie), Boghossian, N.S. (Nansi S.), Burton, V.J. (Vera Joanna), Cortés, M. (Margarita), Katikaneni, L.D. (Lakshmi D.), Larson, J.C.G. (Jennifer C.G.), Angulo, A.S. (Abigail S.), Joshi, J. (Jyoti), Nesin, M. (Mirjana), Padula, M.A. (Michael A.), Kochhar, S. (Sonali), and Connery, A.K. (Amy K.)
Published: 2019
Full Text: View/download PDF

137. General treatment principles for fracture-related infection: recommendations from an international expert group

Author: Metsemakers, W.-J. (Willem-Jan), Morgenstern, M. (Mario), Senneville, E. (Eric), Borens, O. (Olivier), Govaert, G.A.M. (Geertje), Onsea, J. (Jolien), Depypere, M. (Melissa), Richards, R.G. (Geoff), Trampuz, A. (Andrej), Verhofstad, M.H.J. (Michiel), Kates, S.L. (Stephen), Raschke, M.J. (Michael), McNally, M.A. (Martin), Obremskey, W.T. (William), Metsemakers, W.-J. (Willem-Jan), Morgenstern, M. (Mario), Senneville, E. (Eric), Borens, O. (Olivier), Govaert, G.A.M. (Geertje), Onsea, J. (Jolien), Depypere, M. (Melissa), Richards, R.G. (Geoff), Trampuz, A. (Andrej), Verhofstad, M.H.J. (Michiel), Kates, S.L. (Stephen), Raschke, M.J. (Michael), McNally, M.A. (Martin), and Obremskey, W.T. (William)
Abstract: Fracture-related infection (FRI) remains a challenging complication that creates a heavy burden for orthopaedic trauma patients, their families and treating physicians, as well as for healthcare systems. Standardization of the diagnosis of FRI has been poor, which made the undertaking and comparison of studies difficult. Recently, a consensus definition based on diagnostic criteria for FRI was published. As a well-established diagnosis is the first step in the treatment process of FRI, such a definition should not only improve the quality of published reports but also daily clinical practice. The FRI consensus group recently developed guidelines to standardize treatment pathways and outcome measures. At the center of these recommendations was the implementation of a multidisciplinary team (MDT) approach. If such a team is not available, it is recommended to refer complex cases to specialized centers where a MDT is available and physicians are experienced with the treatment of FRI. This should lead to appropriate use of antimicrobials and standardization of surgical strategies. Furthermore, an MDT could play an important role in host optimization. Overall two main surgical concepts are considered, based on the fact that fracture fixation devices primarily target fracture consolidation and can be removed after healing, in contrast to periprosthetic joint infection were the implant is permanent. The first concept consists of implant retention and the second consists of implant removal (healed fracture) or implant exchange (unhealed fracture). In both cases, deep tissue sampling for microbiological examination is mandatory. Key aspects of the surgical management of FRI are a thorough debridement, irrigation with normal saline, fracture stability, dead space management and adequate soft tissue coverage. The use of local antimicrobials needs to be strongly considered. In case of FRI, empiric broad-spectrum antibiotic therapy should be started after tissue sampling. Therea
Published: 2019
Full Text: View/download PDF

138. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Author: Noordam, R. (Raymond), Bos, M.M. (Maxime M.), Wang, H. (Heming), Winkler, T.W. (Thomas W.), Bentley, A.R. (Amy), Kilpeläinen, T.O. (Tuomas O.), Vries, P.S. (Paul) de, Sung, Y.J. (Yun Ju), Schwander, K., Cade, B., Manning, A.K. (Alisa), Aschard, H. (Hugues), Brown, M.R., Chen, H. (Han), Franceschini, N. (Nora), Musani, S.K. (Solomon K.), Richard, M. (Melissa), Vojinović, D. (Dina), Aslibekyan, S. (Stella), Bartz, T.M. (Traci M.), de Las Fuentes, L. (Lisa), Feitosa, M.F. (Mary Furlan), Horimoto, A.R. (Andrea R.), Ilkov, M. (Marjan), Kho, M. (Minjung), Kraja, A. (Aldi), Li, C. (Changwei), Lim, E. (Elise), Liu, Y. (YongMei), Mook-Kanamori, D.O. (Dennis O.), Rankinen, T. (Tuomo), Tajuddin, S.M. (Salman M.), Spek, A. (Ashley) van der, Wang, Z. (Zhe), Marten, J. (Jonathan), Laville, V. (Vincent), Alver, M. (Maris), Evangelou, E. (Evangelos), Graff, M.E. (Maria E.), He, M. (Meian), Kuhnel, B. (Brigitte), Lyytikäinen, L.-P. (Leo-Pekka), Marques-Vidal, P. (Pedro), Nolte, I.M. (Ilja), Palmer, N.D. (Nicholette), Rauramaa, R. (Rainer), Shu, X.-O. (Xiao-Ou), Snieder, H. (Harold), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Adolfo, C. (Correa), Ballantyne, C. (Christie), Bielak, L.F. (Lawrence F.), Biermasz, N.R., Boerwinkle, E.A. (Eric), Dimou, N. (Niki), Eiriksdottir, G. (Gudny), Gao, C. (Chuan), Gharib, S.A. (Sina), Gottlieb, D.J. (Daniel J.), Haba-Rubio, J. (José), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heinzer, R. (Raphaël), Hixson, J.E. (James E.), Homuth, G. (Georg), Ikram, M.A. (Arfan), Komulainen, P. (Pirjo), Krieger, J.E. (José), Lee, J. (Jiwon), Liu, J. (Jingmin), Lohman, K.K. (Kurt K.), Luik, A.I. (Annemarie), Mägi, R. (Reedik), Martin, L.W. (Lisa), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Nalls, M.A. (Michael), O´Connell, J.R., Peters, A. (Annette), Peyser, P.A. (Patricia A.), Raitakari, O. (Olli), Reiner, A. (Alexander), Rensen, P.C.N. (Patrick), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Roenneberg, T., Rotter, J.I. (Jerome I.), Schreiner, P.J. (Pamela), Shikany, J. (James), Sidney, S.S. (Stephen S.), Sims, M. (Mario), Sitlani, C.M. (Colleen M.), Sofer, T. (Tamar), Strauch, K. (Konstantin), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Völzke, H. (Henry), Waldenberger, M. (Melanie), Wallance, R.B. (Robert B.), van Dijk, K.W. (Ko Willems), Yu, C. (Caizheng), Zonderman, A.B. (Alan B.), Becker, D.M. (Diane), Elliott, P. (Paul), Esko, T. (Tõnu), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), North, K.E. (Kari), Penninx, B.W.J.H. (Brenda), Vollenweider, P. (Peter), Wagenknecht, L.E. (Lynne), Wu, T. (Tangchun), Xiang, Y.-B. (Yong-Bing), Zheng, W. (Wei), Arnett, D.K. (Donna), Bouchard, C. (Claude), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Kardia, S.L.R. (Sharon), Kelly, T.N. (Tanika N.), Kritchevsky, S.B. (Stephen), Loos, R.J.F. (Ruth), Pereira, A. (A.), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rotimi, C. (Charles), Zhu, X. (Xiaofeng), Amin, N. (Najaf), Cupples, L.A. (L Adrienne), Fornage, M. (Myriam), Fox, E.F. (Ervin F.), Guo, X. (Xiuqing), Gauderman, W.J. (W James), Rice, K.M. (Kenneth), Kooperberg, C. (Charles), Munroe, P. (Patricia), Liu, C.-T. (Ching-Ti), Morrison, A.C. (Alanna), Rao, D.C. (Dabeeru C.), Heemst, D. (Diana) van, Redline, S. (Susan), Noordam, R. (Raymond), Bos, M.M. (Maxime M.), Wang, H. (Heming), Winkler, T.W. (Thomas W.), Bentley, A.R. (Amy), Kilpeläinen, T.O. (Tuomas O.), Vries, P.S. (Paul) de, Sung, Y.J. (Yun Ju), Schwander, K., Cade, B., Manning, A.K. (Alisa), Aschard, H. (Hugues), Brown, M.R., Chen, H. (Han), Franceschini, N. (Nora), Musani, S.K. (Solomon K.), Richard, M. (Melissa), Vojinović, D. (Dina), Aslibekyan, S. (Stella), Bartz, T.M. (Traci M.), de Las Fuentes, L. (Lisa), Feitosa, M.F. (Mary Furlan), Horimoto, A.R. (Andrea R.), Ilkov, M. (Marjan), Kho, M. (Minjung), Kraja, A. (Aldi), Li, C. (Changwei), Lim, E. (Elise), Liu, Y. (YongMei), Mook-Kanamori, D.O. (Dennis O.), Rankinen, T. (Tuomo), Tajuddin, S.M. (Salman M.), Spek, A. (Ashley) van der, Wang, Z. (Zhe), Marten, J. (Jonathan), Laville, V. (Vincent), Alver, M. (Maris), Evangelou, E. (Evangelos), Graff, M.E. (Maria E.), He, M. (Meian), Kuhnel, B. (Brigitte), Lyytikäinen, L.-P. (Leo-Pekka), Marques-Vidal, P. (Pedro), Nolte, I.M. (Ilja), Palmer, N.D. (Nicholette), Rauramaa, R. (Rainer), Shu, X.-O. (Xiao-Ou), Snieder, H. (Harold), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Adolfo, C. (Correa), Ballantyne, C. (Christie), Bielak, L.F. (Lawrence F.), Biermasz, N.R., Boerwinkle, E.A. (Eric), Dimou, N. (Niki), Eiriksdottir, G. (Gudny), Gao, C. (Chuan), Gharib, S.A. (Sina), Gottlieb, D.J. (Daniel J.), Haba-Rubio, J. (José), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heinzer, R. (Raphaël), Hixson, J.E. (James E.), Homuth, G. (Georg), Ikram, M.A. (Arfan), Komulainen, P. (Pirjo), Krieger, J.E. (José), Lee, J. (Jiwon), Liu, J. (Jingmin), Lohman, K.K. (Kurt K.), Luik, A.I. (Annemarie), Mägi, R. (Reedik), Martin, L.W. (Lisa), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Nalls, M.A. (Michael), O´Connell, J.R., Peters, A. (Annette), Peyser, P.A. (Patricia A.), Raitakari, O. (Olli), Reiner, A. (Alexander), Rensen, P.C.N. (Patrick), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Roenneberg, T., Rotter, J.I. (Jerome I.), Schreiner, P.J. (Pamela), Shikany, J. (James), Sidney, S.S. (Stephen S.), Sims, M. (Mario), Sitlani, C.M. (Colleen M.), Sofer, T. (Tamar), Strauch, K. (Konstantin), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Völzke, H. (Henry), Waldenberger, M. (Melanie), Wallance, R.B. (Robert B.), van Dijk, K.W. (Ko Willems), Yu, C. (Caizheng), Zonderman, A.B. (Alan B.), Becker, D.M. (Diane), Elliott, P. (Paul), Esko, T. (Tõnu), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), North, K.E. (Kari), Penninx, B.W.J.H. (Brenda), Vollenweider, P. (Peter), Wagenknecht, L.E. (Lynne), Wu, T. (Tangchun), Xiang, Y.-B. (Yong-Bing), Zheng, W. (Wei), Arnett, D.K. (Donna), Bouchard, C. (Claude), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Kardia, S.L.R. (Sharon), Kelly, T.N. (Tanika N.), Kritchevsky, S.B. (Stephen), Loos, R.J.F. (Ruth), Pereira, A. (A.), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rotimi, C. (Charles), Zhu, X. (Xiaofeng), Amin, N. (Najaf), Cupples, L.A. (L Adrienne), Fornage, M. (Myriam), Fox, E.F. (Ervin F.), Guo, X. (Xiuqing), Gauderman, W.J. (W James), Rice, K.M. (Kenneth), Kooperberg, C. (Charles), Munroe, P. (Patricia), Liu, C.-T. (Ching-Ti), Morrison, A.C. (Alanna), Rao, D.C. (Dabeeru C.), Heemst, D. (Diana) van, and Redline, S. (Susan)
Abstract: Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.
Published: 2019
Full Text: View/download PDF

139. Conditional deletion of melanin-concentrating hormone receptor 1 from GABAergic neurons increases locomotor activity

Author: Chee, M. (Melissa), Hebert, A.J. (Alex J.), Briançon, N. (Nadege), Flaherty, S.E. (Stephen E.), Pissios, P. (Pavlos), Maratos-Flier, E. (Eleftheria), Chee, M. (Melissa), Hebert, A.J. (Alex J.), Briançon, N. (Nadege), Flaherty, S.E. (Stephen E.), Pissios, P. (Pavlos), and Maratos-Flier, E. (Eleftheria)
Abstract: Objective: Melanin-concentrating hormone (MCH) plays a key role in regulating energy balance. MCH acts via its receptor MCHR1, and MCHR1 deletion increases energy expenditure and locomotor activity, which is associated with a hyperdopaminergic state. Since MCHR1 expression is widespread, the neurons supporting the effects of MCH on energy expenditure are not clearly defined. There is a high density of MCHR1 neurons in the striatum, and these neurons are known to be GABAergic. We thus det
Published: 2019
Full Text: View/download PDF

140. Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission

Author: Guo, H. (Hui), Li, Y. (Ying), Shen, L. (Lu), Wang, T. (Tianyun), Jia, X. (Xiangbin), Liu, L. (Lijuan), Xu, T. (Tao), Ou, M. (Mengzhu), Hoekzema, K. (Kendra), Wu, H. (Huidan), Gillentine, M.A. (Madelyn A.), Liu, C. (Cenying), Ni, H. (Hailun), Peng, P. (Pengwei), Zhao, R. (Rongjuan), Zhang, Y. (Yu), Phornphutkul, C. (Chanika), Stegmann, A.P.A. (Alexander P.A.), Prada, C.E. (C.), Hopkin, R., Shieh, J.T. (Joseph T.), McWalter, K. (Kirsty), Monaghan, K.G. (Kristin G.), Hasselt, P.M. (Peter) van, van Gassen, K. (Koen), Bai, T. (Ting), Long, M. (Min), Han, L. (Lin), Quan, Y. (Yingting), Chen, M. (Meilin), Zhang, Y. (Yaowen), Li, K. (Kuokuo), Zhang, Q. (Qiumeng), Tan, J. (Jieqiong), Zhu, T. (Tengfei), Liu, Y. (Yaning), Pang, N. (Nan), Peng, J. (Jing), Scott, D.A., Lalani, S.R. (Seema R.), Azamian, M. (Mahshid), Mancini, G.M.S. (Grazia), Adams, D.J. (Darius J.), Kvarnung, M. (Malin), Lindstrand, A. (Anna), Nordgren, A. (Ann), Pevsner, J. (Jonathan), Osei-Owusu, I.A. (Ikeoluwa A.), Romano, C. (Corrado), Calabrese, G. (Giuseppe), Galesi, O. (O.), Gecz, J. (Jozef), Haan, E. (Eric), Ranells, J. (Judith), Racobaldo, M. (Melissa), Nordenskjöld, M., Madan-Khetarpal, S. (Suneeta), Sebastian, J. (Jessica), Ball, S. (Susie), Zou, X. (Xiaobing), Zhao, J. (Jingping), Hu, Z. (Zhengmao), Xia, F. (Fan), Liu, P. (Pengfei), Rosenfeld, J.A. (Jill), Vries, B. (Boukje) de, Bernier, R.A. (Raphael A.), Xu, Z.-Q.D. (Zhi-Qing David), Li, H. (Honghui), Xie, W. (Wei), Hufnagel, R.B. (Robert B.), Eichler, E.E. (Evan), Xia, K. (Kun), Guo, H. (Hui), Li, Y. (Ying), Shen, L. (Lu), Wang, T. (Tianyun), Jia, X. (Xiangbin), Liu, L. (Lijuan), Xu, T. (Tao), Ou, M. (Mengzhu), Hoekzema, K. (Kendra), Wu, H. (Huidan), Gillentine, M.A. (Madelyn A.), Liu, C. (Cenying), Ni, H. (Hailun), Peng, P. (Pengwei), Zhao, R. (Rongjuan), Zhang, Y. (Yu), Phornphutkul, C. (Chanika), Stegmann, A.P.A. (Alexander P.A.), Prada, C.E. (C.), Hopkin, R., Shieh, J.T. (Joseph T.), McWalter, K. (Kirsty), Monaghan, K.G. (Kristin G.), Hasselt, P.M. (Peter) van, van Gassen, K. (Koen), Bai, T. (Ting), Long, M. (Min), Han, L. (Lin), Quan, Y. (Yingting), Chen, M. (Meilin), Zhang, Y. (Yaowen), Li, K. (Kuokuo), Zhang, Q. (Qiumeng), Tan, J. (Jieqiong), Zhu, T. (Tengfei), Liu, Y. (Yaning), Pang, N. (Nan), Peng, J. (Jing), Scott, D.A., Lalani, S.R. (Seema R.), Azamian, M. (Mahshid), Mancini, G.M.S. (Grazia), Adams, D.J. (Darius J.), Kvarnung, M. (Malin), Lindstrand, A. (Anna), Nordgren, A. (Ann), Pevsner, J. (Jonathan), Osei-Owusu, I.A. (Ikeoluwa A.), Romano, C. (Corrado), Calabrese, G. (Giuseppe), Galesi, O. (O.), Gecz, J. (Jozef), Haan, E. (Eric), Ranells, J. (Judith), Racobaldo, M. (Melissa), Nordenskjöld, M., Madan-Khetarpal, S. (Suneeta), Sebastian, J. (Jessica), Ball, S. (Susie), Zou, X. (Xiaobing), Zhao, J. (Jingping), Hu, Z. (Zhengmao), Xia, F. (Fan), Liu, P. (Pengfei), Rosenfeld, J.A. (Jill), Vries, B. (Boukje) de, Bernier, R.A. (Raphael A.), Xu, Z.-Q.D. (Zhi-Qing David), Li, H. (Honghui), Xie, W. (Wei), Hufnagel, R.B. (Robert B.), Eichler, E.E. (Evan), and Xia, K. (Kun)
Abstract: RNA binding proteins are key players in posttranscriptional regulation and have been implicated in neurodevelopmental and neuropsychiatric disorders. Here, we report a significant burden of heterozygous, likely genedisrupting variants in CSDE1 (encoding a highly constrained RNA binding protein) among patients with autism and related neurodevelopmental disabilities. Analysis of 17 patients identifies common phenotypes including autism, intellectual disability, language and motor delay, seizures, macrocephaly, and variable ocular abnormalities. HITSCLIP revealed that Csde1binding targets are enriched in autismassociated gene sets, especially FMRP targets, and in neuronal development and synaptic plasticity–related pathways. Csde1 knockdown in primary mouse cortical neurons leads to an overgrowth of the neurites and abnormal dendritic spine morphology/synapse formation and impaired synaptic transmission, whereas mutant and knockdown experiments in Drosophila result in defects in synapse growth and synaptic transmission. Our study defines a new autismrelated syndrome and highlights the functional role of CSDE1 in synapse development and synaptic transmission.
Published: 2019
Full Text: View/download PDF

141. Food choices: concordance in Australian children aged 11-12 years and their parents

Author: Vivarini, P. (Prudence), Kerr, J.A. (Jessica), Clifford, S.A. (Susan ), Grobler, A.C. (Anneke C.), Jansen, P.W. (Pauline), Mensah, F.K.F. (Fane ), Baur, L.A. (Louise A.), Gibbons, K. (Kay), Wake, M. (Melissa), Vivarini, P. (Prudence), Kerr, J.A. (Jessica), Clifford, S.A. (Susan ), Grobler, A.C. (Anneke C.), Jansen, P.W. (Pauline), Mensah, F.K.F. (Fane ), Baur, L.A. (Louise A.), Gibbons, K. (Kay), and Wake, M. (Melissa)
Abstract: OBJECTIVES: Snack foods-typically high in salt, sugar, fat and/or energy-are likely important to the obesity epidemic. In the context of a population-based health assessment involving parent-child dyads at child age 11-12 years, we report cross-generational concordance in intake at a controlled snack food observation. DESIGN: Cross-sectional study (Child Health CheckPoint), nested within the Longitudinal Study of Australian Children. SETTING: Assessment centres in seven Australian cities, February 2015-March 2016. PARTICIPANTS: Of all participating CheckPoint families (n=1874), 1299 children (50.3% girls) and 1274 parents (85.9% mothers) with snack data were included. Survey weights and methods were applied to account for the clustered multistage sample design. OUTCOME MEASURES: Partway through the 3.5-hour assessment, parents and children attended Food Stop separately for a timed 15 min 'snack break'. One of four standardised box size/content combinations was randomly provided to all participants on any given day. Total food mass, energy, nutrients and sodium consumed was measured to the nearest 1 g. Pearson's correlation coefficients and adjusted multivariable linear regression models assessed parent-child concordance in each variable. RESULTS: Children consumed less grams (151 g [SD 80] vs 165 g [SD 79]) but more energy (1393 kJ [SD 537] vs 1290 kJ [SD 658]) than parents. Parent-child concordance coefficients were small, ranging from 0.07 for sodium intake to 0.17 for carbohydrate intake. Compared with children with parents' energy intake on the 10th centile, children whose parents were on the 90th centile ate on average 227 kJ more. If extrapolated to one similar unsupervised snack on a daily basis, this equates to an additional 83 050 kJ per year, which could have a cumulative impact on additional body fat. CONCLUSIONS: Although modest at an individual level, this measured parent-child concordance in unsupervised daily snack situations could account for substan
Published: 2019
Full Text: View/download PDF

142. Association of pazopanib-induced toxicities with outcome of patients with advanced soft tissue sarcoma; a retrospective analysis based on the European Organisation for Research and Treatment of Cancer (EORTC) 62043 and 62072 clinical trials

Author: Vos, M (Melissa), Sleijfer, Stefan, Litiere, S, Touati, N, Duffaud, F, van der Graaf, WT, Gelderblom, H, Vos, M (Melissa), Sleijfer, Stefan, Litiere, S, Touati, N, Duffaud, F, van der Graaf, WT, and Gelderblom, H
Published: 2019

143. Children's abilities and strategies in managing the facial display of affect

Author: Halberstadt, Amy G., Grotjohn, D. Kirk, Johnson, Cheryl A., Furth, Meredith Swanson, and Greig, M. Melissa
Published: 1992
Full Text: View/download PDF

144. Religious supplicant, seductive cannibal, or reflex machine? In search of the praying mantis

Author: Prete, Frederick R. and Wolfe, M. Melissa
Published: 1992
Full Text: View/download PDF

145. A Site-Specific, Sustained-Release Drug Delivery System for Aneurysmal Subarachnoid Hemorrhage

Author: Herbert J. Faleck, Angela R. Stella, Michele Turner, M. Melissa Peet, Hans Jakob Steiger, R. Loch Macdonald, Tom Tice, Parissa Heshmati, Nima Etminan, Cara R. Davis, Bruce W. Hudson, Mark D. Johnson, Daniel Hänggi, and Kevin Burton
Subjects: Male, Drug, medicine.medical_specialty, Neurology, Subarachnoid hemorrhage, media_common.quotation_subject, 030204 cardiovascular system & hematology, 03 medical and health sciences, Dogs, 0302 clinical medicine, Cerebrospinal fluid, medicine, Animals, Pharmacology (medical), cardiovascular diseases, Microparticle, Nimodipine, media_common, Pharmacology, business.industry, Brain, Infusion Pumps, Implantable, Subarachnoid Hemorrhage, medicine.disease, Rats, Treatment Outcome, medicine.anatomical_structure, Delayed-Action Preparations, Anesthesia, Toxicity, Original Article, Female, Neurology (clinical), Subarachnoid space, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Nimodipine is the only drug approved for use by the Food and Drug Administration for improving outcome after aneurysmal subarachnoid hemorrhage (SAH). It has less than optimal efficacy, causes dose-limiting hypotension in a substantial proportion of patients, and is administered enterally 6 times daily. We describe development of site-specific, sustained-release nimodipine microparticles that can be delivered once directly into the subarachnoid space or cerebral ventricles for potential improvement in outcome of patients with aneurysmal SAH. Eight injectable microparticle formulations of nimodipine in poly(DL-lactide-co-glycolide) (PLGA) polymers of varying composition were tested in vitro, and 1 was advanced into preclinical studies and clinical application. Intracisternal or intraventricular injection of nimodipine–PLGA microparticles in rats and beagles demonstrated dose-dependent, sustained concentrations of nimodipine in plasma and cerebrospinal fluid for up to 29 days with minimal toxicity in the brain or systemic tissues at doses
Published: 2016

146. Learning history and cholinergic modulation in the dorsal hippocampus are necessary for rats to infer the status of a hidden event

Author: M. Melissa Flesher, Michael S. Fanselow, Aaron P. Blaisdell, Nathanial A. Nocera, and Cynthia D. Fast
Subjects: Visual perception, Cognitive Neuroscience, media_common.quotation_subject, 05 social sciences, Inference, Cognition, Ambiguity, Human brain, Hippocampal formation, Cholinergic modulation, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, medicine, 0501 psychology and cognitive sciences, Psychology, Immediate early gene, Neuroscience, 030217 neurology & neurosurgery, media_common
Abstract: Identifying statistical patterns between environmental stimuli enables organisms to respond adaptively when cues are later observed. However, stimuli are often obscured from detection, necessitating behavior under conditions of ambiguity. Considerable evidence indicates decisions under ambiguity rely on inference processes that draw on past experiences to generate predictions under novel conditions. Despite the high demand for this process and the observation that it deteriorates disproportionately with age, the underlying mechanisms remain unknown. We developed a rodent model of decision-making during ambiguity to examine features of experience that contribute to inference. Rats learned either a simple (positive patterning) or complex (negative patterning) instrumental discrimination between the illumination of one or two lights. During test, only one light was lit while the other relevant light was blocked from physical detection (covered by an opaque shield, rendering its status ambiguous). We found experience with the complex negative patterning discrimination was necessary for rats to behave sensitively to the ambiguous test situation. These rats behaved as if they inferred the presence of the hidden light, responding differently than when the light was explicitly absent (uncovered and unlit). Differential expression profiles of the immediate early gene cFos indicated hippocampal involvement in the inference process while localized microinfusions of the muscarinic antagonist, scopolamine, into the dorsal hippocampus caused rats to behave as if only one light was present. That is, blocking cholinergic modulation prevented the rat from inferring the presence of the hidden light. Collectively, these results suggest cholinergic modulation mediates recruitment of hippocampal processes related to past experiences and transfer of these processes to make decisions during ambiguous situations. Our results correspond with correlations observed between human brain function and inference abilities, suggesting our experiments may inform interventions to alleviate or prevent cognitive dysfunction. © 2015 Wiley Periodicals, Inc.
Published: 2016

147. Long-term prognostic outcomes and implication of oral anticoagulants in patients with new-onset atrial fibrillation following st-segment elevation myocardial infarction.

Author: Madsen, Jasmine Melissa, Jacobsen, Mia Ravn, Sabbah, Muhammad, Topal, Divan Gabriel, Jabbari, Reza, Glinge, Charlotte, Køber, Lars, Torp-Pedersen, Christian, Pedersen, Frants, Sørensen, Rikke, Holmvang, Lene, Engstrøm, Thomas, Lønborg, Jacob Thomsen, Madsen, Jasmine M Melissa, Jacobsen, Mia R Ravn, Topal, Divan G Gabriel, and Lønborg, Jacob T Thomsen
Abstract: Background: New-onset atrial fibrillation (NEW-AF) following ST-segment elevation myocardial infarction (STEMI) is a common complication, but the true prognostic impact of NEW-AF is unknown. Additionally, the optimal treatment of NEW-AF among patients with STEMI is warranted.Methods: A large cohort of consecutive patients with STEMI treated with percutaneous coronary intervention were identified using the Eastern Danish Heart Registry from 1999-2016. Medication and end points were retrieved from Danish nationwide registries. NEW-AF was defined as a diagnosis of AF within 30 days following STEMI. Patients without a history of AF and alive after 30 days after discharge were included. Incidence rates were calculated and multivariate analyses performed to determine the association between NEW-AF and long-term mortality, incidence of ischemic stroke, re-MI, and bleeding leading to hospitalization, and the comparative effectiveness of OAC therapy on these outcomes.Results: Of 7944 patients with STEMI, 296 (3.7%) developed NEW-AF. NEW-AF was associated with increased long-term mortality (adjusted HR 1.48, 95% CI 1.20-1.82, P<.001) and risk of bleeding leading to hospitalization (adjusted HR 1.36, 95% CI 1.00-1.85, P=.050), and non-significant increased risk of ischemic stroke (adjusted HR 1.45, 95% CI 0.96-2.19, P=.08) and re-MI (adjusted HR 1.14, 95% CI 0.86-1.52, P=.35) with a median follow-up of 5.8 years. In NEW-AF patients, 38% received OAC therapy, which was associated with reduced long-term mortality (adjusted HR 0.69, 95% CI 0.47-1.00, P=.049).Conclusions: NEW-AF following STEMI is associated with increased long-term mortality. Treatment with OAC therapy in NEW-AF patients is associated with reduced long-term mortality. [ABSTRACT FROM AUTHOR]
Published: 2021
Full Text: View/download PDF

148. Pharmacokinetics of a weekly transdermal delivery system of tenofovir alafenamide in hairless rats

Author: M. Melissa Peet, Onkar N. Singh, Vivek Agrahari, Gustavo F. Doncel, Ying Jiang, Xinyi Gao, Meredith R. Clark, Ajay K. Banga, and Wei Zhang
Subjects: Sexual transmission, Drug Compounding, Rats, Hairless, Administration, Oral, Transdermal Patch, Pharmaceutical Science, 02 engineering and technology, Pharmacology, Administration, Cutaneous, Antiviral Agents, Proof of Concept Study, 030226 pharmacology & pharmacy, Tenofovir alafenamide, Drug Administration Schedule, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Animals, Medicine, Tissue Distribution, Tenofovir, Adverse effect, Transdermal, Alanine, business.industry, Adenine, Prodrug, 021001 nanoscience & nanotechnology, Hairless, Delayed-Action Preparations, Injections, Intravenous, Vagina, Drug delivery, Female, 0210 nano-technology, business
Abstract: Tenofovir alafenamide (TAF) is a potent prodrug of tenofovir (TFV) for HIV prophylaxis, and HIV and HBV treatment. Compared to oral daily doses, transdermal administration of TAF may be more advantageous for long-term adherence by offering sustained drug delivery and reduced dosing frequency. Here, we described the plasma pharmacokinetics (PK) of an optimized once-weekly suspension transdermal delivery system (TDS) for TAF (96 mg/25 cm2 of TDS) in female hairless rats. Over the study period, the TAF TDS delivered an overall low level of TAF (median: 1.43 [0.02-3.28] ng/mL) and a sustained level of the stable metabolite and parent drug, TFV. Relative to the projected exposure corresponding to six-day oral daily doses, a comparable TAF exposure but a substantially lower TFV exposure was resulted from the TAF TDS, suggesting a lower risk of TFV-associated adverse effects. TAF, TFV, and phosphorylated TFVs (TFV-monophosphate and diphosphate) were found distributed in vaginal tissue, the portal of entry for HIV during male-to-female sexual transmission. Skin adhesion and tolerance were acceptable given the animal model used. PK evaluation of the TAF TDS in hairless rats demonstrates the proof of concept that transdermal delivery can be an alternative route for a sustained, once-weekly systemic delivery of TAF.
Published: 2020

149. Food Footprint as a Measure of Sustainability for Grazing Dairy Farms

Author: Behin Elahi, Matthew R. Herman, A. Pouyan Nejadhashemi, J. Sebastian Hernandez-Suarez, Mohammad Abouali, K. A. Cassida, Timothy M. Harrigan, Fariborz Daneshvar, Sabah Anwer Dawood Al Masraf, and M. Melissa Rojas-Downing
Subjects: Michigan, Profit (accounting), Farms, 010504 meteorology & atmospheric sciences, Climate, Forest management, 010501 environmental sciences, Environment, 01 natural sciences, Footprint, Agricultural science, Grazing, Animals, Economic impact analysis, Animal Husbandry, 0105 earth and related environmental sciences, Carbon Footprint, Global and Planetary Change, Measure (data warehouse), Ecology, business.industry, Sustainable Development, Pollution, Dairying, Milk, Sustainability, Environmental science, Livestock, Cattle, Female, business
Abstract: Livestock productions require significant resources allocation in the form of land, water, energy, air, and capital. Meanwhile, owing to increase in the global demand for livestock products, it is wise to consider sustainable livestock practices. In the past few decades, footprints have emerged as indicators for sustainability assessment. In this study, we are introducing a new footprint measure to assess sustainability of a grazing dairy farm while considering carbon, water, energy, and economic impacts of milk production. To achieve this goal, a representative farm was developed based on grazing dairy practices surveys in the State of Michigan, USA. This information was incorporated into the Integrated Farm System Model (IFSM) to estimate the farm carbon, water, energy, and economic impacts and associated footprints for ten different regions in Michigan. A multi-criterion decision-making method called VIKOR was used to determine the overall impacts of the representative farms. This new measure is called the food footprint. Using this new indicator, the most sustainable milk production level (8618 kg/cow/year) was identified that is 19.4% higher than the average milk production (7215 kg/cow/year) in the area of interest. In addition, the most sustainable pasture composition was identified as 90% tall fescue with 10% white clover. The methodology introduced here can be adopted in other regions to improve sustainability by reducing water, energy, and environmental impacts of grazing dairy farms, while maximizing the farm profit and productions.
Published: 2018

150. The IEO-OS in the Mediterranean Sea: Contributions of the RADMED monitoring program to the knowledge of the system

Author: Balbín, R. (Rosa), García-Martínez, M.C. (María del Carmen), Aparicio-González, A. (Alberto), Caínzos, V. (Verónica), Jiménez-Aparicio, J.A. (Juan Antonio), Martín-Quetglas, M. (Melissa), Melguizo, J., Mena, C. (Catalina), Moya-Ruiz, F. (Francisca), Piñeiro, S. (Safo), Santiago, R. (Rocío), Serra-Tur, M. (Mariano), Tel, E. (Elena), and Vargas-Yáñez, M. (Manuel)
Subjects: Centro Oceanográfico de Baleares, Medio Marino y Protección Ambiental
Published: 2018
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

624 results on '"M. Melissa"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources