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1. Proteomic analyses of primary human villous trophoblasts exposed to flame retardant BDE-47 using SWATH-MS

Author

Chen, Hao, Williams, Katherine E, Kwan, Elaine Y, Kapidzic, Mirhan, Puckett, Kenisha A, San, Ali, Fisher, Susan J, and Robinson, Joshua F

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Clinical Research, Endocrine Disruptors, Women's Health, Social Determinants of Health, Biotechnology, Contraception/Reproduction, Pediatric, Perinatal Period - Conditions Originating in Perinatal Period, 2.1 Biological and endogenous factors, Generic health relevance, Reproductive health and childbirth, Humans, Pregnancy, Female, Placenta, Halogenated Diphenyl Ethers, Trophoblasts, Flame Retardants, Proteome, Proteomics, Flame retardants, Cytotrophoblasts, Pharmacology and Pharmaceutical Sciences, Toxicology, Pharmacology and pharmaceutical sciences
Abstract

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants and recognized developmental toxicants that are detectable in placental tissues. Higher levels of in utero PBDE exposure have been associated with an increased risk of adverse birth outcomes. During pregnancy, cytotrophoblasts (CTBs) from the placenta play critical roles in the formation of the maternal-fetal interface via uterine invasion and vascular remodeling. The differentiation of these cells towards an invasive phenotype is crucial for proper placental development. We previously have shown that BDE-47 can impact CTB viability and hinder the ability of these cells to migrate and invade. To expand on potential toxicological mechanisms, we utilized quantitative proteomic approaches to identify changes in the global proteome of mid-gestation primary human CTBs after exposure to BDE-47. Using sequential window acquisition of all theoretical fragment-ion spectra (SWATH), we identified 3024 proteins in our CTB model of differentiation/invasion. Over 200 proteins were impacted as a function of BDE-47 exposure (1 μM and 5 μM) across the treatment period (15, 24, and 39 h). The differentially expressed molecules displayed time- and concentration-dependent changes in expression and were enriched in pathways associated with aggregatory and adhesive processes. Network analysis identified CYFIP1, a molecule previously unexplored in a placental context, to be dysregulated at BDE-47 concentrations previously seen to impact CTB migration/invasion. Our SWATH-MS dataset thus demonstrates BDE-47 impacts the global proteome of differentiating CTBs and serves as a valuable resource for further understanding of the relationship between environmental chemical exposures and placental development and function. AVAILABILITY OF DATA AND MATERIAL: Raw chromatograms are deposited on the MassIVE proteomic database (https://massive.ucsd.edu) under accession number MSV000087870. Normalized relative abundances are also available as Table S1.

Published
2023

2. Organophosphate Flame Retardants, Highly Fluorinated Chemicals, and Biomarkers of Placental Development and Disease During Mid-Gestation

Author

Varshavsky, Julia R, Robinson, Joshua F, Zhou, Yan, Puckett, Kenisha A, Kwan, Elaine, Buarpung, Sirirak, Aburajab, Rayyan, Gaw, Stephanie L, Sen, Saunak, Gao, Songmei, Smith, Sabrina Crispo, Park, June-Soo, Zakharevich, Igor, Gerona, Roy R, Fisher, Susan J, and Woodruff, Tracey J

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Pediatric, Endocrine Disruptors, Women's Health, Maternal Health, Pregnancy, Contraception/Reproduction, Aetiology, 2.1 Biological and endogenous factors, Reproductive health and childbirth, Good Health and Well Being, Biomarkers, Female, Flame Retardants, Humans, Organophosphates, Placenta, Placentation, flame retardants, perfluoroalkyl and polyfluoralkyl substances, biomonitoring, developmental/reproductive health effects, endocrine disruption, preeclampsia, pregnancy complications, maternal health, birth outcomes, cytotrophoblast differentiation, Pharmacology and Pharmaceutical Sciences, Toxicology, Pharmacology and pharmaceutical sciences
Abstract

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) are chemicals that may contribute to placenta-mediated complications and adverse maternal-fetal health risks. Few studies have investigated these chemicals in relation to biomarkers of effect during pregnancy. We measured 12 PFASs and four urinary OPFR metabolites in 132 healthy pregnant women during mid-gestation and examined a subset with biomarkers of placental development and disease (n = 62). Molecular biomarkers included integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and matrix metalloproteinase-1 (MMP1). Morphological endpoints included potential indicators of placental stress and the extent of cytotrophoblast (CTB)-mediated uterine artery remodeling. Serum PFASs and urinary OPFR metabolites were detected in ∼50%-100% of samples. The most prevalent PFASs were perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), with geometric mean (GM) levels of ∼1.3-2.8 (95% confidence limits from 1.2-3.1) ng/ml compared to ≤0.5 ng/ml for other PFASs. Diphenyl phosphate (DPhP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the most prevalent OPFR metabolites, with GMs of 2.9 (95% CI: 2.5-3.4) and 3.6 (95% CI: 2.2-3.1) ng/ml, respectively, compared to

Published
2021

3. Association of polybrominated diphenyl ether (PBDE) levels with biomarkers of placental development and disease during mid-gestation

Author

Varshavsky, Julia R, Robinson, Joshua F, Zhou, Yan, Puckett, Kenisha A, Kwan, Elaine, Buarpung, Sirirak, Aburajab, Rayyan, Gaw, Stephanie L, Sen, Saunak, Smith, Sabrina Crispo, Frankenfield, Julie, Park, June-Soo, Fisher, Susan J, and Woodruff, Tracey J

Subjects
Epidemiology, Public Health, Health Sciences, Perinatal Period - Conditions Originating in Perinatal Period, Contraception/Reproduction, Pediatric, Prevention, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Good Health and Well Being, Adult, Biomarkers, Female, Fetus, Halogenated Diphenyl Ethers, Humans, Liver, Maternal Exposure, Placenta, Placentation, Pregnancy, Pregnancy Complications, Pregnancy Outcome, San Francisco, Young Adult, Flame retardants, Biomonitoring, Developmental, reproductive health effects, Endocrine disruption, Preeclampsia, Pregnancy complications, Maternal health, Birth outcomes, Cytotrophoblast differentiation, Developmental/reproductive health effects, Public Health and Health Services, Toxicology, Public health
Abstract

BackgroundPolybrominated diphenyl ether (PBDE) exposures have been associated with adverse pregnancy outcomes. A hypothesized mechanism is via alterations in placental development and function. However, we lack biomarkers that can be used as early indicators of maternal/fetal response to PBDE exposures and/or perturbations in placental development or function.MethodsTo evaluate the relationship between PBDE levels and placental biomarkers during mid-gestation of human pregnancy (n = 62), we immunolocalized three molecules that play key roles in cytotrophoblast (CTB) differentiation and interstitial/endovascular uterine invasion-integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and metalloproteinase-1 (MMP1)-and assessed three morphological parameters as potential indicators of pathological alterations using H&E-stained tissues-leukocyte infiltration, fibrinoid deposition, and CTB endovascular invasion. We evaluated associations between placental PBDE levels and of biomarkers of placental development and disease using censored Kendall's tau correlation and linear regression methods.ResultsPBDEs were detected in all placental samples. We observed substantial variation in antigen expression and morphological endpoints across placental regions. We observed an association between PBDE concentrations and immunoreactivity of endovascular CTB staining with anti-ITGA1 (inverse) or interstitial CTBs staining with anti-CDH5 (positive).ConclusionsWe found several molecular markers that may be sensitive placental indicators of PBDE exposure. Further, this indicates that placental biomarkers of development and disease could be useful barometers of exposure to PBDEs, a paradigm that could be extended to other environmental chemicals and placental stage-specific antigens.

Published
2020

4. Glycaemic control and microvascular complications among paediatric type 2 diabetes mellitus patients in Hong Kong at 2 years after diagnosis.

Author

Yam, W. I., Wong, Shirley M. Y., Cheung, P. T., Kwan, Elaine Y. W., Lam, Y. Y., Wong, L. M., Ng, K. L., Wong, Sammy W. C., Lee, C. Y., Tay, M. K., Chan, K. T., Fu, Antony C. C., Tung, Joanna Y. L., Pang, Gloria S. W., Yau, H. C., See, Queenie W. S., Lo, Priscilla W. C., To, Sharon W. Y., Yuen, H. W., and Chung, Jacky Y. K.

Published
2024
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5. Early-life inflammation primes a T helper 2 cell-fibroblast niche in skin

Author

Boothby, Ian C., Kinet, Maxime J., Boda, Devi P., Kwan, Elaine Y., Clancy, Sean, Cohen, Jarish N., Habrylo, Ireneusz, Lowe, Margaret M., Pauli, Mariela, Yates, Ashley E., Chan, Jamie D., Harris, Hobart W., Neuhaus, Isaac M., McCalmont, Timothy H., Molofsky, Ari B., and Rosenblum, Michael D.

Subjects
T cells -- Physiological aspects, Inflammation -- Physiological aspects, Fibroblasts -- Physiological aspects, Skin -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Inflammation early in life can prime the local immune milieu of peripheral tissues, which can cause lasting changes in immunological tone that confer disease protection or susceptibility.sup.1. The cellular and molecular mechanisms that prompt changes in immune tone in many nonlymphoid tissues remain largely unknown. Here we find that time-limited neonatal inflammation induced by a transient reduction in neonatal regulatory T cells causes a dysregulation of subcutaneous tissue in mouse skin. This is accompanied by the selective accumulation of type 2 helper T (T.sub.H2) cells within a distinct microanatomical niche. T.sub.H2 cells are maintained into adulthood through interactions with a fibroblast population in skin fascia that we refer to as T.sub.H2-interacting fascial fibroblasts (TIFFs), which expand in response to T.sub.H2 cytokines to form subcutaneous fibrous bands. Activation of the T.sub.H2-TIFF niche due to neonatal inflammation primes the skin for altered reparative responses to wounding. Furthermore, we identify fibroblasts in healthy human skin that express the TIFF transcriptional signature and detect these cells at high levels in eosinophilic fasciitis, an orphan disease characterized by inflammation and fibrosis of the skin fascia. Taken together, these data define a previously unidentified T.sub.H2 cell niche in skin and functionally characterize a disease-associated fibroblast population. The results also suggest a mechanism of immunological priming whereby inflammation early in life creates networks between adaptive immune cells and stromal cells to establish an immunological set-point in tissues that is maintained throughout life. Time-limited skin inflammation in neonatal mice promotes a reciprocal interaction between type 2 helper T cells and fascial fibroblasts that regulates wound repair in later life., Author(s): Ian C. Boothby [sup.1] [sup.2] , Maxime J. Kinet [sup.3] , Devi P. Boda [sup.1] , Elaine Y. Kwan [sup.1] [sup.4] , Sean Clancy [sup.1] , Jarish N. Cohen [...]

Published
2021
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7. Incidence and Predictors for Oncologic Etiologies in Chinese Children with Pituitary Stalk Thickening

Author

Li, Mario W. T., primary, Poon, Sarah W. Y., additional, Cheung, Claudia, additional, Wong, Chris K. C., additional, Shing, Matthew M. K., additional, Chow, Terry T. W., additional, Lee, Samantha L. K., additional, Pang, Gloria S. W., additional, Kwan, Elaine Y. W., additional, Poon, Grace W. K., additional, Yau, Ho-Chung, additional, Tung, Joanna Y. L., additional, and Liu, Anthony P. Y., additional

Published
2023
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11. Review on the Screening of Urine Glucose in School Children and Adolescents With Obesity for Early Diagnosis of Type 2 Diabetes Mellitus in Hong Kong

Author

Pang, Gloria S W, primary, Lee, Ching-Yin, additional, Fu, Antony C C, additional, Tsang, Jennifer Wing-Yan, additional, Yau, Kent H C, additional, Belaramani, Kiran, additional, Wong, Lap Ming, additional, But, Betty W M, additional, Chow, Jasmine C K, additional, Wong, Shirley M Y, additional, Cheung, Patrick C H, additional, Lo, Priscilla W C, additional, Ng, Kwok- Leung, additional, Tung, Joanna Y L, additional, Poon, Sarah W Y, additional, Chan, Kwong Tat, additional, Chan, Angela M K, additional, Wong, Sammy W C, additional, Tay, Ming-Kut, additional, Chung, Ying Ki, additional, Lam, Yuen Yu, additional, and Kwan, Elaine Y W, additional

Published
2021
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12. Additional file 1 of Association of polybrominated diphenyl ether (PBDE) levels with biomarkers of placental development and disease during mid-gestation

Author

Varshavsky, Julia R., Robinson, Joshua F., Zhou, Yan, Puckett, Kenisha A., Kwan, Elaine, Sirirak Buarpung, Aburajab, Rayyan, Gaw, Stephanie L., Saunak Sen, Smith, Sabrina Crispo, Frankenfield, Julie, June-Soo Park, Fisher, Susan J., and Woodruff, Tracey J.

Abstract

Additional file 1: Table S1. Molecular and morphological biomarkers of placental disease and development during mid-gestation. Table S2. Primary antibodies used for immunolocalization assessments. Table S3. Molecular immunoreactivity and low/high PBDE exposure by placental region/cell type during mid-gestation (n = 62). Table S4. Detection frequencies for 19 PBDE congeners in matched samples of maternal serum, placenta, and fetal liver during mid-gestation (n = 130). Table S5. Correlation (unadjusted p-value)a of molecular and morphological biomarkers during mid-gestation (n = 62). Table S6. Correlation (FDR estimate)a of molecular and morphological placental biomarkers during mid-gestation (n = 62). Table S7. Correlation (unadjusted p-values and FDR)a of placental biomarkers and wet-weight PBDE levels during mid-gestation (n = 62).

Published
2020
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13. Additional file 2 of Association of polybrominated diphenyl ether (PBDE) levels with biomarkers of placental development and disease during mid-gestation

Author

Varshavsky, Julia R., Robinson, Joshua F., Zhou, Yan, Puckett, Kenisha A., Kwan, Elaine, Sirirak Buarpung, Aburajab, Rayyan, Gaw, Stephanie L., Saunak Sen, Smith, Sabrina Crispo, Frankenfield, Julie, June-Soo Park, Fisher, Susan J., and Woodruff, Tracey J.

Subjects
embryonic structures
Abstract

Additional file 2: Figure S1. Diagram of study framework illustrating approach to evaluating relationships between biomarkers of chemical exposure and potential biomarkers of placental development and disease. Figure S2. Immunoreactivity of ITGA1 at the maternal-fetal interface. Representative images of floating (A-C) and anchoring (D-F) villi, interstitial invading CTBs (CTBi) of the decidua (G-I), and endovascular CTBs (CTBe) lining a uterine artery (J-L). Tissue sections of 2nd trimester samples were immunostained for ITGA1 (green) and co-stained with anti-CK (trophoblast marker, red) and DAPI (nuclear dye, blue). Images represent typical profiles of ITGA1 expression. Bars = 100 μm. Figure S3. Immunoreactivity of CDH5 at the maternal-fetal interface. Representative images of floating (A-C) and anchoring (D-F) villi, interstitial invading CTBs (CTBi) of the decidua (G-I), and endovascular CTBs (CTBe) lining a uterine artery (J-L). Tissue sections of 2nd trimester samples were immunostained for ITGA1 (green) and co-stained with anti-CK (trophoblast marker, red) and DAPI (nuclear dye, blue). Images represent typical profile of CDH5 expression. Bars = 100 μm. Figure S4. Immunoreactivity of MMP1 at the maternal-fetal interface. Representative images of floating (A-C) and anchoring (D-F) villi, interstitial invading CTBs (CTBi) of the decidua (G-I), and endovascular CTBs (CTBe) lining a uterine artery (J-L). Tissue sections of 2nd trimester samples were immunostained for ITGA1 (green) and co-stained with anti-CK (trophoblast marker, red) and DAPI (nuclear dye, blue). Images represent typical profile of MMP1 expression. Bars = 100 μm. Figure S5. Representative morphological features of the maternalfetal interface. Representative images of morphological features that were scored in human placental biopsies: (A) perivillous fibrinoid deposition surrounding floating villi, (B) fibrinoid deposition, (C) leukocyte (white blood cell) infiltration of the basal plate, and (D) CTB remodeling of uterine arteries. Black arrows and dotted black lines indicate the feature of interest.

Published
2020
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16. Drosophila p53 Binds a Damage Response Element at the reaper Locus

Author

Brodsky, Michael H., Nordstrom, William, Tsang, Garson, Kwan, Elaine, Rubin, Gerald M., and Abrams, John M.

Subjects
Radiation, Tumor proteins, Drosophila, Biological sciences
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/S0092-8674(00)80627-3 Byline: Michael H Brodsky (1), William Nordstrom (2), Garson Tsang (1), Elaine Kwan (1), Gerald M Rubin (1), John M Abrams (2) Abstract: The tumor suppressor gene p53 regulates multiple cellular responses to DNA damage, but the transcriptional targets that specify these responses are incompletely understood. We describe a Drosophila p53 homolog and demonstrate that it can activate transcription from a promoter containing binding sites for human p53. Dominant-negative forms of Drosophila p53 inhibit both transactivation in cultured cells and radiation-induced apoptosis in developing tissues. The cis-regulatory region of the proapoptotic gene reaper contains a radiation-inducible enhancer that includes a consensus p53 binding site. Drosophila p53 can activate transcription from this site in yeast and a multimer of this site is sufficient for radiation induction in vivo. These results indicate that reaper is a direct transcriptional target of Drosophila p53 following DNA damage. Author Affiliation: (1) Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA (2) Department of Cell Biology, University of Texas, Southwestern Medical Center, Dallas, Texas 75390, USA Article History: Received 3 March 2000; Revised 10 March 2000

Published
2000

17. PHYL acts to down-regulate TTK88, a transcriptional repressor of neuronal cell fates, by a SINA-dependent mechanism

Author

Tang, Amy H., Neufeld, Thomas P., Kwan, Elaine, and Rubin, Gerald M.

Subjects
Drosophila -- Physiological aspects, Metabolic regulation -- Research, Biological sciences
Abstract

Researchers have analyzed the functional relationship between the Seven In Absentia (SINA), Phyllopod (PHYL) and Tramtrack (TTK88) proteins. Particular attention was given to the regulation of TTK88 during Drosophila eye development. It was possible to establish that induction of PHYL expression prompts down-regulation of TTK88 by a process which needs SINA. TTK88 was found to be a repressor of photoreceptor cell fate determination. PHYL links with SINA to target TTK88 for degradation, thus forming a permissive environment for photoreceptor differentiation.

Published
1997

18. Global proteomic analyses of human cytotrophoblast differentiation/invasion.

Author

Hao Chen, Williams, Katherine E., Kwan, Elaine Y., Kapidzic, Mirhan, Puckett, Kenisha A., Aburajab, Rayyan K., Robinson, Joshua F., and Fisher, Susan J.

Subjects
GLOBAL analysis (Mathematics), FETAL development, CELL differentiation, PROTEOMICS, DECIDUA, FETUS
Abstract

During human pregnancy, cytotrophoblasts (CTBs) from the placenta differentiate into specialized subpopulations that play crucial roles in proper fetal growth and development. A subset of these CTBs differentiate along an invasive pathway, penetrating the decidua and anchoring the placenta to the uterus. A crucial hurdle in pregnancy is the ability of these cells to migrate, invade and remodel spiral arteries, ensuring adequate blood flow to nourish the developing fetus. Although advances continue in describing the molecular features regulating the differentiation of these cells, assessment of their global proteomic changes at mid-gestation remain undefined. Here, using sequential window acquisition of all theoretical fragment-ion spectra (SWATH), which is a data-independent acquisition strategy, we characterized the protein repertoire of second trimester human CTBs during their differentiation towards an invasive phenotype. This mass spectrometry-based approach allowed identification of 3026 proteins across four culture time points corresponding to sequential stages of differentiation, confirming the expression dynamics of established molecules and offering new information into other pathways involved. The availability of a SWATH CTB global spectral library serves as a beneficial resource for hypothesis generation and as a foundation for further understanding CTB differentiation dynamics. [ABSTRACT FROM AUTHOR]

Published
2021
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19. The Influence of Foodscape on Young Generations’ Satisfaction and Behavioral Intentions in Cafés, Johor Bahru, Malaysia

Author

Sang-Hyeop Lee, Kwan Elaine, and Jong-Ho Lee

Subjects
Generation y, Service quality, Hospitality, business.industry, Beverage industry, General Earth and Planetary Sciences, Advertising, Customer satisfaction, Business, Marketing, General Environmental Science
Abstract

In the food and beverage industry, foodscape is known as an important component in satisfy the customer and return patronage. However, it has been overlooked in the restaurant service quality as well as less examined in the hospitality journal. Thus, it causes that the restaurant managers have little knowledge on how the foodscape influences customer satisfaction as well as behavioral intention. Therefore, the purpose of this study is to analyze the role of foodscape attributes on customer satisfaction and behavioral intention in cafe in Johor Bahru, Malaysia. The sample size of the questionnaire in this study was 322 respondents who are Generation Y in the age group between 18 and 35 years old. Multiple regression was used in the study to identify the relative importance of foodscape attributes that lead to customer satisfaction and behavioral intention. Through this research, the restaurant managers would aware and realize that foodscape would have relationships between customer satisfaction as well as behavioral intention.

Published
2015

21. An MMP liberates the Ninjurin A ectodomain to signal a loss of cell adhesion

Author

Shuning Zhang, Dailey, Gina M., Kwan, Elaine, Glasheen, Bernadette M., Sroga, Gyna E., and Page-McCaw, Andrea

Subjects
Cell adhesion -- Analysis, Drosophila -- Genetic aspects, Drosophila -- Research, Homeostasis -- Analysis, Membrane proteins -- Research, Metalloproteins -- Structure, Metalloproteins -- Research, Biological sciences
Abstract

The identification of NijA, a transmembrane protein whose vertebrate homologs regulate cell adhesion, as a two-hybrid binding partner of Mmp1 is reported. Data indicate that Mmp1 releases the N-terminal extracellular domain of NijA and this liberated ectodomain promotes the loss of cell adhesion in a cell-nonautonomous manner.

Published
2006

22. Prevalence and Penetrance of Germline BRCA1 and BRCA2 Mutations in a Population Series of 649 Women with Ovarian Cancer

Author

Risch, Harvey A., McLaughlin, John R., Cole, David E. C., Rosen, Barry, Bradley, Linda, Kwan, Elaine, Jack, Elaine, Vesprini, Danny J., Kuperstein, Graciela, Abrahamson, John L. A., Fan, Isabel, Wong, Betty, and Narod, Steven A.

Subjects
Human genetics -- Research, Gene mutations -- Testimonials, Breast cancer -- Genetic aspects, Ovarian cancer -- Genetic aspects, Biological sciences
Published
2001

24. Diagnosis of 5α-Reductase 2 Deficiency: Is Measurement of Dihydrotestosterone Essential?

Author

Chan, Angel On Kei, primary, But, Betty Wai Man, primary, Lee, Ching Yin, primary, Lam, Yuen Yu, primary, Ng, Kwok Leung, primary, Tung, Joanna Yuet Ling, primary, Kwan, Elaine Yin Wah, primary, Chan, Yuk Kit, primary, Tsui, Teresa Kam Chi, primary, Lam, Almen Lai Na, primary, Tse, Wing Yee, primary, Cheung, Pik To, primary, and Shek, Chi Chung, primary

Published
2013
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26. BRCA mutations in Italian breast/ovarian cancer families

Author

Nedelcu, Raluca, primary, Liede, Alexander, additional, Aubé, Jennifer, additional, Finch, Amy, additional, Kwan, Elaine, additional, Jack, Elaine, additional, Narod, Steven A., additional, Randall, Susan, additional, Hugel, Lara, additional, and Clark, Katherine, additional

Published
2002
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28. Global analysis of patterns of gene expression during Drosophila embryogenesis

Author

Tomancak, Pavel, Berman, Benjamin, Beaton, Amy, Weiszmann, Richard, Kwan, Elaine, Hartenstein, Volker, Celniker, Susan, and Rubin, Gerald

Abstract

Background Cell and tissue specific gene expression is a defining feature of embryonic development in multi-cellular organisms. However, the range of gene expression patterns, the extent of the correlation of expression with function, and the classes of genes whose spatial expression are tightly regulated have been unclear due to the lack of an unbiased, genome-wide survey of gene expression patterns.Results We determined and documented embryonic expression patterns for 6,003 (44%) of the 13,659 protein-coding genes identified in the Drosophila melanogaster genome with over 70,000 images and controlled vocabulary annotations. Individual expression patterns are extraordinarily diverse, but by supplementing qualitative in situ hybridization data with quantitative microarray time-course data using a hybrid clustering strategy, we identify groups of genes with similar expression. Of 4,496 genes with detectable expression in the embryo, 2,549 (57%) fall into 10 clusters representing broad expression patterns. The remaining 1,947 (43%) genes fall into 29 clusters representing restricted expression, 20% patterned as early as blastoderm, with the majority restricted to differentiated cell types, such as epithelia, nervous system, or muscle. We investigate the relationship between expression clusters and known molecular and cellular-physiological functions.Conclusion Nearly 60% of the genes with detectable expression exhibit broad patterns reflecting quantitative rather than qualitative differences between tissues. The other 40% show tissue-restricted expression; the expression patterns of over 1,500 of these genes are documented here for the first time. Within each of these categories, we identified clusters of genes associated with particular cellular and developmental functions.

Published
2007
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29. Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

Author

Dmitri Nepogodiev, Joana Ff Simoes, Elizabeth Li, Maria Picciochi, James C Glasbey, Glauco Baiocchi, Ruth Blanco-Colino, Daoud Chaudhry, Ehab AlAmeer, Kariem El-Boghdadly, Funmilola Wuraola, Dhruva Ghosh, Rohan R Gujjuri, Ewen M Harrison, Herman Lule, Haytham Kaafarani, Mohammad Khosravi, Irmgard Kronberger, Sezai Leventoğlu, Harvinder Mann, Kenneth A Mclean, Mengistu Gebreyohanes Mengesha, Maria Marta Modolo, Faustin Ntirenganya, Lisa Norman, Oumaima Outani, Riinu Pius, Peter Pockney, Ahmad Uzair Qureshi, April Camilla Roslani, Sohei Satoi, Catherine Shaw, Aneel Bhangu, Omar M Omar, Waheed-Ul-Rahman Ahmed, Leah Argus, Alasdair Ball, Edward P Bywater, Amanpreet Brar, Brett E Dawson, Irani Duran, Muhammed Elhadi, Conor S Jones, Sivesh K Kamarajah, James M Keatley, Samuel Lawday, Ella J Marson, Riinu Ots, Irène Santos, Elliott H Taylor, Isobel M Trout, Chris Varghese, Mary L Venn, William Xu, Irida Dajti, Arben Gjata, Salah Eddine Oussama Kacimi, Luis Boccalatte, Daniel Cox, Philip Townend, Felix Aigner, Irmgard Elisabeth Kronberger, Elgun Samadov, Amer Alderazi, Kamral Hossain, Greg Padmore, Gabrielle van Ramshorst, Ismaïl Lawani, Anis Cerovac, Samir Delibegovic, Gustavo Mendonça Ataíde Gomes, Igor Lima Buarque, Muhammad Gohar, Mihail Slavchev, Chukwuemeka Nwegbu, Arnav Agarwal, Janet Martin, Joshua Ng-Kamstra, Maricarmen Olivos, Wenhui Lou, Dong-Lin Ren, Jose Andres Calvache, Carlos J Perez Rivera, Ana Danic Hadzibegovic, Tomislav Kopjar, Jakov Mihanovic, Pablo Mijahil Avilés Jiménez, Nikolaos Gouvas, Jaroslav Klat, René Novysedlák, Nicolas Amisi, Peter Christensen, Alaa El-Hussuna, Sylvia Batista, Eddy Lincango-Naranjo, Sameh Emile, Danilo Alfonso Arévalo Sandoval, Hailu Dhufera, Samuel Hailu, Mengistu G Mengesha, Joonas H Kauppila, Alexis P Arnaud, Zaza Demetrashvili, Markus Albertsmeier, Hans Lederhuber, Markus W Löffler, Daniel Kwesi Acquah, Bernard Ofori, Stephen Tabiri, Symeon Metallidis, Georgios Tsoulfas, Maria-Lorena Aguilera-Arevalo, Gustavo Recinos, Tamás Mersich, Dániel Wettstein, Gabriele Kembuan, Peiman Brouki Milan, Mohammad Hossein Khosravi, Masoud Mozafari, Ahmed Hilmi, Helen Mohan, Oded Zmora, Gaetano Gallo, Francesco Pata, Gianluca Pellino, Yuki Fujimoto, Naoto Kuroda, Mohamad K Abou Chaar, Faris Ayasra, Ildar Fakhradiyev, Intisar Hisham Said Hamdun, Jang Jin-Young, Mohammad Jamal, Lina Karout, Aiste Gulla, Fanjandrainy Rasoaherinomenjanahary, Luc Hervé Samison, Iran Irani Durán Sánchez, Diana Samantha Gonzalez, Laura Martinez, María José Martínez, Alejandra Nayen, Antonio Ramos-De la Medina, Jade Nunez, Pueya Rashid Nashidengo, Rakesh Shah, Ashish Lal Shrestha, Pascal Jonker, Schelto Kruijff, Milou Noltes, Pieter Steinkamp, Deborah Wright, Lukman Abdur-Rahman, Adesoji Ademuyiwa, Adewale Adisa, Babatunde Osinaike, Justina Seyi-Olajide, Omolara Williams, Emmanuel Williams, Sofija Pejkova, Zainab Al Balushi, Raza Sayyed, Mustafa Abo Mohsen, Sadi A Abukhalaf, Moises Cukier, Hugo Gomez-Fernandez, Sebastian Shu Yip, Ximena Paola Vasquez Ojeda, Marie Dione Sacdalan, Piotr Major, José Azevedo, Miguel F Cunha, Ahmad Zarour, Eduard-Alexandru Bonci, Ionut Negoi, Sergey Efetov, Viktor Kochetkov, Andrey Litvin, Jc Allen Ingabire, Georges Bucyibaruta, Ntirenganya Faustin, Sosthene Habumuremyi, Alphonsine Imanishimwe, Haragirimana Jean de Dieu, Emmanuel Munyaneza, Isaie Ncogoza, Ehab Alameer, Abdourahmane Ndong, Dejan Radenkovic, Min Hoe Chew, Frederick Koh, James Ngu, Arpád Panyko, Uros Bele, Jurij Aleš Košir, Hassan Daoud, Ana Maria Minaya Bravo, Umesh Jayarajah, Dakshitha Wickramasinghe, Mohammed Elmujtba Adam Essa Adam, Martin Rutegård, Malin Sund, Michel Adamina, Eleftherios Gialamas, Karoline Horisberger, Muhammad Alshaar, Abel Huang, Varut Lohsiriwat, Shane Charles, Haithem Jlassi, Arda Isik, Hervé Monka Lekuya, Slava Kopetskyi, Hayder Alsaadi, Sattar Alshryda, Osaid Alser, Brittany Bankhead-Kendall, Kerry Breen, Hassan Mashbari, Fernando Bonilla Cal, Hamza Al-Naggar, Mayaba Maimbo, Dennis Mazingi, Tom 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Ugarte Oscco, Gian Mendiola, Yahaira Tatiana Carpio Colmenares, Carlos Shiraishi Zapata, Maria Rosa Ortiz, Marie Dione Sacdalan, Piotr Major, Filipe Castro Borges, Octavio Viveiros, Pedro Serralheiro, Paulo Santos-Costa, Filipa Mendes, Miguel Rocha Melo, Paulo Cardoso, Ana Soares, José Azevedo, Rita Gonçalves Pereira, Nelson Silva, André Caiado, Maria Luís Sacras, Pedro Azevedo, Rui Almeida-Reis, Miguel F Cunha, João Oliveira, Jorge Nogueiro, Mafalda Sampaio-Alves, Luciana Cidade Costa, Catarina Baía, Ana Cláudia Deus, Rita Branquinho, André Marçal, André Tojal, Ahmad Zarour, Ahmad Zarour, Silviu Tiberiu Makkai-Popa, Aurel Mironescu, Florin Grama, Elena Adelina Toma, Ionut Negoi, Daniela Filipescu, Nicolae Bacalbasa, Natalia Motas, Sebastian Ionescu, Octav Ginghina, Radu Costea, Narcis Octavian Zarnescu, Radu Drasovean, Eduard-Alexandru Bonci, Mihail-Gabriel Dimofte, Vlad Porumb, Mikhail Kirov, Yegor Molitvin, Andrey Litvin, Vadim Pykhteev, Marianna Raevskaya, Sergey Efetov, Aleksandr Butyrskii, Mushabab Alshahrani, Azah Althumairi, Nasser Alzerwi, Ahmed Al Ameer, Ahmed Al Ameer, Tariq Madkhali, Abddulrahman Saleh Almulhim, Salman Ghazwani, Abdu Ayoub, Othman Iskander, Mohammed Ghunaim, Mohammed Alharthi, Turki M Alzaidi, Azah Althumairi, Mohammad Alyami, Abdulrahman Al Amri, Azah Althumairi, Abdullah AlFakhri, Amal Alhefdhi, Sharfuddin Chowdhury, Thamer Nouh, Ameen Alshehri, Abdulrahman Alzahrani, Yousef Alalawi, Selmy Awad, Ibrahima Konate, Abdourahmane Ndong, Jacques Tendeng, Nan Zun Teo, Frederick Koh, Jurij Aleš Košir, Uros Bele, Sabra Aqil, Cristina Barrena López, Ana Sánchez Mozo, Antonio Rodriguez Infante, Patricia Caja Vivancos, Mikel Prieto, Igor Alberdi San Roman, Laura Gomez Fernandez, Josep Maria Muñoz Vives, Anna Carreras-Castañer, Berta Díaz-Feijoo, Ramon Sieira-Gil, Victor Turrado-Rodriguez, Anna Sánchez López, Santiago Sánchez-Cabús, Marta Jimenez Toscano, MªPilar Canals Sin, Saura García Laura, Oriol Martin Sole, Pedro Palazon Bellver, Sonia Pérez-Bertólez, Jordi Prat-Ortells, Mireia Riba Martínez, Josep Rubio-Palau, Xavier Tarrado, Jorge Nuñez, Veronica Alonso Mendoza, Coro Bescós, Eloy Espin-Basany, Martin Espinosa-Bravo, Daniel Gil-Sala, Susana González-Suárez, Nuria Montferrer Estruch, Jorge Nuñez, Lucia Porteiro Mariño, Ana Rodríguez-Tesouro, Fabian Rojas Portilla, M Pilar Tormos Pérez, Inmaculada Vives, Unai Garcia De Cortazar, Kiara Tudela, Aitor Landaluce-Olavarria, Mercedes Estaire Gómez, Jorge Almoguera, Bakarne Ugarte-Sierra, Virginia Jimenez, Marta Bertrand, Laura Cárdenas Puiggrós, Olga Delisau-Puig, Jorge Garcia-Adamez, David Julià Bergkvist, Eloy Maldonado-Marcos, Lucia Diego García, Marta Roldón Golet, Iván Soto-Darias, Aida Cristina Rahy-Martín, Diego Enjuto, Adolfo Ramos-Luengo, Juan Delgado Fernandez, Carolina Lugo Duarte, Cristina Ojeda Thies, Lucila Marquez, Diana Crego Vita, Jana Dziakova, Ana Maria Minaya Bravo, Jorge Caño Velasco, Olga Mateo-Sierra, Begoña Quintana-Villamandos, Cristina Rey Valcarcel, Javier Rio, Laura Román García de León, Marcello Di Martino, Jorge Prada, Javier Serrano González, Manuel Losada, Jose Tomas Castell Gomez, Ramon Corripio-Sanchez, Alexander Forero-Torres, José Manuel Morales-Puebla, Hanna Perez-Chrzanowska, Santiago Valderrabano Gonzalez, Alvaro Yebes, Ignacio Zapardiel, Manuel Diez Alonso, Nelson Morales Palacios, Alberto Cabañero Sánchez, Fátima Sánchez Fernández, Alfredo Abad Gurumeta, Ane Abad-Motos, Fernando Corella, Javier Ripollés-Melchor, Rosa Sanz-Gonzalez, Marta Alcaraz Fuentes, Maria Teresa Fernández Martín, Pablo Calvo Espino, Milagros Carrasco Prats, Antonio-José Fernández-López, Damián García Escudero, Vanesa Garcia Soria, Jesús Aarón Martínez Alonso, Miguel Ruiz-Marín, Beatriz Gómez Pérez, Joaquin Moya-Angeler, Daniel Fernández Martínez, Heura Llaquet Bayo, Enrique Colás-Ruiz, Susana Bella Romera, M Teresa Gavaldà Pellicé, Misericòrdia Jordà Solé, Enrique Jose Ruiz Velasquez, Bernardo Núñez, Raul Jimenez, Jon Zabaleta, Maria Jose González-Gimeno, Irene Ortega Vázquez, Antonio Perez Ferrer, Rubén Martín-Láez, Marcelo Moreno Suarez, Miguel Angel Freiria Eiras, Irene Ramallo-Solís, Juan-Carlos Gomez-Rosado, Jose Ramon Oliver Guillen, Mar Achalandabaso Boira, Juan Carlos Catalá Bauset, Julio Domenech, Rafael Badenes, Juan Carlos Bernal-Sprekelsen, Jorge Sancho-Muriel, Beatriz De Andrés-Asenjo, Francisco J Tejero-Pintor, Marc Vallve-Bernal, Alba Vazquez Melero, Laura Sánchez Blasco, Jorge Escartin, Victoria Duque Mallén, Selvaratnam Srishankar, Umesh Jayarajah, Charitha Sooriyabandara, Oshan Basnayake, Nalaka Gunawansa, Dakshitha Wickramasinghe, Prabuth Dulanjan Weeraddana, Thanusan Vimalakanthan, Shanthamoorthy Gishanthan, Pramodh Chandrasinghe, Eleftherios Gialamas, Marc-Olivier Sauvain, Ahmad Ghazal, Yusra Al-Sabbagh, Turki Alhassoun, Sara Maa Albared, Antoine Naem, Hareth Alnahr, Ghassan Jisry, Ali Hammed, Arda Isik, Okedi Francis Xaviour, Gaston Turinawe, Isaac Mubezi, Franck K Sikakulya, Andrew Kakeeto, Wilberforce M Kabweru, Hervé Monka Lekuya, Ronald Kiweewa, Herman Lule, Paul Matovu, Otolia Isaac, Mohamed Mashhour, Amin El Helw, Sattar Alshryda, Safeena Kherani, Awadelkarim Mohamed, Ferial Mohamed Ali Abbas, Diary Mohammed, Ehab Aldlyami, Rakesh Kundra, Mohamed Mashhour, Mohamed Mashhour, Antony Louis Rex Michael, Hayder Alsaadi, Kareem S Khalil, Rachel Dbeis, Shafaque Shaikh, Jenny Ferry, Aiman Jamal, Haleema Siddique, Rishi Das, Nikhil Ponugoti, Sivesh K Kamarajah, Pornjittra Rattanasirivilai, Asma Sultana, Frances Mosley, Matthew Chan, Antony Bateman, Gareth Davies-Jones, Fanourios Georgiades, Grant D Stewart, Navid Ahmadi, Aman Coonar, Mariam Baig, Chetan Khatri, Arthika Surendran, Julian Sonksen, Robert Sinnerton, Caitlin Brennan, Gemma Faulkner, Michael Greenhalgh, Hannah Emerson, Kiran Singisetti, Joshua Totty, Michael Wilson, Terence Lo, Harriet Corbett, Ijeoma Okonkwo, Gill Arbane, Kariem El-Boghdadly, Cyrus Kerawala, Chetan Parmar, Tom Abbott, Michael Bath, Funlayo Odejinmi, Jayesh Sagar, Rishi Talwar, Samuel Newman, John Hammond, John Moir, Natalie Duric, Tamas Szakmany, Ahmar Iftikhar Talib, Mina Youssef, Christopher Lewis-Lloyd, Christopher Lewis-Lloyd, Mariam Lami, Khurram Ayub, Benjamin Dean, Supriya Balasubramanya, Sathya Lakpriya, Luke Rogers, Paul Turner, Mark Maher, Kohila Sigamoney, John Edwards, Jihène El Kafsi, John Hardie, David Johnson, Christin Henein, Marianne Hollyman, Ketan Agarwal, Simon Powell, Govind Singh Chauhan, Rakesh Patel, Joel Gagnier, Heather Carmichael, Aurora, Kristofor A Olson, Eric Etchill, Joseph Incorvia, Sameer Hirji, Matthew Naunheim, Frederick Drake, Haytham Kaafarani, Caroline Reinke, Anna Alecci, Dennis Vaysburg, Jennifer Rodriquez, Emily Shih, Vin Shen Ban, Julia Coleman, Henry E Rice, Krista Kaups-Fresno, Emmanouil Giorgakis, Maggie DiNome, Neal Bhutiani, Omar Alnachoukati, Brittany Bankhead-Kendall, Taylor Aiken, Thomas Diehl, Ankush Gosain, Rishi Rattan, Muhammad Owais Abdul Ghani, Nensi Melissa Ruzgar, Anna Liveris, Nina Glass, Charu Paranjape, Theresa Chin, Antonio Meola, Kristina Nicholson, John Squiers, Stephanie Lueckel, Janani Reisenauer, Rachael Callcut, Ahmed Mansour, Allison Berndtson, Lucy Kornblith, Sara Seegert, Paulo Martins, Hamza Al-Naggar, Mohammed Al-Shehari, Ibrahim Al-Raimi, Allan Ngulube, Maphios Siamuchembu, Willard Mushiwokufa, Busisiwe Mlambo, Simbarashe Chinyowa, Ervis Agastra, Enton Bollano, Kostandin Gjyli, Dariel Thereska, Irida Dajti, Jola Kerpaci, Enxhi Vrapi, Lorena Zijaj, Bahraoui Djahida, Belabbes Fatima Zohra, Kouidri Khadidja, Oussama Bali, Nassim Benallel, Ismahene Lalmi, Meriem Abdoun, Nesrine Aouabed, Souad Bouaoud, Kamel Bouchenak, Assia Haif, Zineddine Soualili, Joaquin Bastet, Agustín Bianco, Daniel Capitaine, Jorge Centeno Lozada, Carlos Esquivel, Rodrigo Figueroa, Manuel Garcia, Pablo Martín García, José Ignacio Gerchunoff, Fernando Martinez Iascano, Jose Mondino, María Emilia Muriel, Carmignani Pablo, Martin Passadore, Alejandra Tornini, Rogelio Traverso, Lara Vargas, Gerardo Zanoni, Norberto Berber, Estefanía Cotta, Marcela Di Vincenzo, Esteban Sebastian Gallino, Cecilia Gigena, Bianca Grassano, Veronica Laudani, Ignacio Lugones, Constanza Madrid, Maximiliano Maricic, Antonio Alberto Martinez, Andres Rosso, Pablo Scher, Sofia Tachella, Damaris Idara Anabel Zezular, Carla Abuawad, Agustin Albani Forneris, Carola Allemand, Laura Gisela Alvarez Calzaretta, Luis Boccalatte, Jorge G Boretto, Rocio Boudou, Rodrigo Brandariz, Martin Buljubasich, Arturo Burchakchi, Martin Buttaro, Juan Pablo Campana, Virginia Cano Busnelli, Tomas Carminatti, Agustina Florencia Castro Lalín, Julian Cereghini, María Sol Crespi Amor, Roberto Sebastián Croattini, Maria Sol Fernandez, Marcelo Figari, Uriel Fraidenraij, Diego Gallegos, Agustín Maria García-Mansilla, Marcos Gonzalez, Matias Ignacio Gonzalez, Esteban Gonzalez Salazar, Jeremias Goransky, Guillermo Hernandez Gauna, Felipe Higuera, Fernando Holc, Esteban Gabriel Jauregui, Juan Larrañaga, Juan Liyo, Lionel Llano, Pablo Lobos, Emilia Luzzi, Gustavo Mastroianni, Santiago Miguel Mata-Suarez, Horacio F Mayer, Santiago Mc Loughlin, Efrain Mendoza, Ricardo Esteban Mentz, Pedro Mercado, Pablo Moyano, Florencia Noll, Diego Odetto, Agustina Rene Oliva, Rafael Perez Vidal, Catalina Poggi, Eduardo Jorge Premoli, María Lourdes Ramos, Patricio Rosas, Luciano Rossi, Gustavo Rossi, Jose Saadi, Jordán Scherñuk, Pablo Slullitel, María Verona Stang, María Victoria Taboada, Sebastian Tirapegui, Constanza Uffelmann, Carlos Vaccaro, Roberto Vagni, Ana Clara Valerio, Celeste Soledad Zarratea, Carina Chwat, Silvina Montal, Brian Morris, Pedro Valdez, Fernando Diaz-Couselo,Ricci C, Casadei R, Fruscio, R, Ornaghi, S, Felice Pecoraro, Emanuele Cammarata, Sofia Campanella, Daniela Canzonieri, Adriana Cordova, Federico De Michele, Ettore Dinoto, Mara Franza, Leo Licari, Daniele Matta, Domenico Mirabella, Roberto Pirrello, Pierfrancesco Pugliese, Fernando Rosatti, Giuseppe Salamone, Francesca Toia, Massimiliano Tripoli, Vito Chiantera, Mariano Catello Di Donna, Collaborative, Covidsurg, Collaborative, Globalsurg, Palmisano, Silvia, de Manzini, Nicolo', Simoes, J, Rosati, R, on behalf of COVIDSurg Collaborative, GlobalSurg Collaborative, Aldrighetti, L, Mortini, P, Olmi, S, Medical Oncology, Assoc Surg Training ASiT, European Soc Coloproctology ESCP, EuroSurg, G4 Alliance, GlobalPaedSurg, GICS, ItSURG, ISRC, Italian Soc Colorectal Surg SICCR, PTSurg, S-ECCO, South African Soc, and SpainSurg

Subjects
Lung Diseases, Male, Internationality, SARS-Cov-2, COVID-19, surgery, pathways, pre-operative isolation, Settore MED/18 - CHIRURGIA GENERALE, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Lung Disease, ESTUDOS PROSPECTIVOS, Cohort Studies, Patient Isolation, Postoperative Complications, 80 and over, Prospective Studies, Prospective cohort study, 610 Medicine & health, Aged, 80 and over, Incidence (epidemiology), Treatment Outcome, Elective Surgical Procedures, Female, Elective Surgical Procedure, Cohort study, Human, medicine.medical_specialty, Isolation (health care), Preoperative care, NO, Anesthesiology, Preoperative Care, medicine, Humans, Elective surgery, LS7_4, Aged, business.industry, pathway, Surgery, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Prospective Studie, Anesthesiology and Pain Medicine, Human medicine, Postoperative Complication, Cohort Studie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p=0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3days, with an OR (95%CI) at 4–7days or ≥8days of 1.25 (1.04–1.48), p=0.015 and 1.31 (1.11–1.55), p=0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p=0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3days, with an OR (95%CI) at 4–7days or ≥8days of 1.25 (1.04–1.48), p=0.015 and 1.31 (1.11–1.55), p=0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care.

Published
2021

30. An MMP liberates the Ninjurin A ectodomain to signal a lossof cell adhesion.

Author

Shuning Zhang, Dailey, Gina M., Kwan, Elaine, Glasheen, Bernadette M., Sroga, Gyna E., and Page-McCaw, Andrea

Subjects
*METALLOPROTEINASES, *METALLOENZYMES, *PROTEINASES, *CELL adhesion, *DROSOPHILA melanogaster
Abstract

Matrix metalloproteinases (MMPs) are important for developmental tissue remodeling and for the inflammatory response. Although the vertebrate MMP family is large and functionally redundant, the fruitfly Drosophila melanogaster has only two MMPs, both essential genes. Our previous work demonstrated that Mmp1 is required for growth of the tracheal system, and we suggested that the mutant phenotype resulted from aberrant persistence of cell adhesion to the extracellular matrix. Here we report the identification of NijA, a transmembrane protein whose vertebrate homologs regulate cell adhesion, as a two-hybrid binding partner for Mmp1. The binding of Mmp1 and NijA was confirmed by coimmunoprecipitation of endogenous proteins from flies, and the endogenous proteins were found to colocalize at the tracheal cell surface in larvae. When NijA is expressed in S2 cells, they lose adhesion to surfaces; this adhesion-loss phenotype is dependent on the expression and catalytic activity of Mmp1. Our data indicate that Mmp1 releases the N-terminal extracellular domain of NijA. This liberated ectodomain promotes the loss of cell adhesion in a cell-nonautonomous manner. We suggest that tracheal cell adhesion is regulated by a novel mechanism utilizing an MMP and a ninjurin family member. [ABSTRACT FROM AUTHOR]

Published
2006
Full Text
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31. An MMP liberates the Ninjurin A ectodomain to signal a loss of cell adhesion.

Author

Zhang S, Dailey GM, Kwan E, Glasheen BM, Sroga GE, and Page-McCaw A

Subjects
Amino Acid Sequence, Animals, Cell Adhesion physiology, Cell Adhesion Molecules, Neuronal genetics, Cell Adhesion Molecules, Neuronal metabolism, Cells, Cultured, Drosophila Proteins genetics, Drosophila melanogaster genetics, Gene Expression Regulation, Developmental, Larva, Matrix Metalloproteinases genetics, Matrix Metalloproteinases immunology, Membrane Proteins genetics, Molecular Sequence Data, Nerve Growth Factors genetics, Nerve Growth Factors metabolism, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Tissue Inhibitor of Metalloproteinases genetics, Tissue Inhibitor of Metalloproteinases metabolism, Trachea cytology, Trachea metabolism, Two-Hybrid System Techniques, Yeasts genetics, Drosophila Proteins metabolism, Matrix Metalloproteinases metabolism, Membrane Proteins metabolism, Signal Transduction
Abstract

Matrix metalloproteinases (MMPs) are important for developmental tissue remodeling and for the inflammatory response. Although the vertebrate MMP family is large and functionally redundant, the fruitfly Drosophila melanogaster has only two MMPs, both essential genes. Our previous work demonstrated that Mmp1 is required for growth of the tracheal system, and we suggested that the mutant phenotype resulted from aberrant persistence of cell adhesion to the extracellular matrix. Here we report the identification of NijA, a transmembrane protein whose vertebrate homologs regulate cell adhesion, as a two-hybrid binding partner for Mmp1. The binding of Mmp1 and NijA was confirmed by coimmunoprecipitation of endogenous proteins from flies, and the endogenous proteins were found to colocalize at the tracheal cell surface in larvae. When NijA is expressed in S2 cells, they lose adhesion to surfaces; this adhesion-loss phenotype is dependent on the expression and catalytic activity of Mmp1. Our data indicate that Mmp1 releases the N-terminal extracellular domain of NijA. This liberated ectodomain promotes the loss of cell adhesion in a cell-nonautonomous manner. We suggest that tracheal cell adhesion is regulated by a novel mechanism utilizing an MMP and a ninjurin family member.

Published
2006
Full Text
View/download PDF

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