131 results on '"Jacobson F"'
Search Results
2. Formate Production by CHO Cells: Biosynthetic Mechanism and Potential Cytotoxicity
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Ihrig, T. J., Maulawizada, M. A., Thomas, B. D., Jacobson, F. S., Beuvery, E. C., editor, Griffiths, J. B., editor, and Zeijlemaker, W. P., editor
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- 1995
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3. Reverse halo sign in pulmonary mucormyosis
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Juan, Y.-H., Saboo, S. S., Lin, Y.-C., Conner, J. R., Jacobson, F. L., and Khandelwal, A.
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- 2014
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4. MA19.03 Sex Differences in the Prediction of Future Lung Cancer Risk Based on a Single Low-Dose Chest Computed Tomography Scan
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Simon, J., Mikhael, P., Tahir, I., Graur, A., Fata, A., Shepard, J.-A., Jacobson, F., Barzilay, R., Sequist, L., Pace, L., and Fintelmann, F.J.
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- 2023
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5. Art and science in the clinical management of the patient with infection and/or cancer
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Jacobson, F. L. and Rubin, R. H.
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- 2004
6. Cell Culture Raw Materials Screening By Calcein-AM Fluorescence Using A 96 Well Plate Format
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Ihrig, T., primary, Tsao, M., additional, Jacobson, F., additional, Sliwkowski, M.B., additional, and Hilton, M., additional
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- 1994
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7. Classification and Representation of Semi-Simple Jordan Algebras
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Jacobson, F. D., Jacobson, N., Rota, Gian-Carlo, editor, and Jacobson, Nathan
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- 1989
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8. Clinical and radiologic disease in smokers with normal spirometry
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Regan, EA, Lynch, DA, Curran-Everett, D, Curtis, JL, Austin, JHM, Grenier, PA, Kauczor, HU, Bailey, WC, De Meo, DL, Casaburi, RH, Friedman, P, Van Beek, EJR, Hokanson, JE, Bowler, RP, Beaty, TH, Washko, GR, Han, MK, Kim, V, Kim, SS, Yagihashi, K, Washington, L, McEvoy, CE, Tanner, C, Mannino, DM, Make, BJ, Silverman, EK, Crapo, JD, Martinez, C, Pernicano, PG, Hanania, N, Alapat, P, Bandi, V, Atik, M, Boriek, A, Guntupalli, K, Guy, E, Parulekar, A, Nachiappan, A, Hersh, C, Jacobson, F, Barr, RG, Thomashow, B, D'Souza, B, Pearson, GDN, Rozenshtein, A, MacIntyre, N, McAdams, HP, Tashjian, J, Wise, R, Hansel, N, Brown, R, Horton, K, Putcha, N, Adami, A, Porszasz, J, Fischer, H, Budoff, M, Cannon, D, Rossiter, H, Sharafkhaneh, A, Lan, C, Wendt, C, Bell, B, Foreman, M, Westney, G, Berkowitz, E, Rosiello, R, Pace, D, Criner, G, Ciccolella, D, Cordova, F, Dass, C, D'Alonzo, R, Desai, P, Jacobs, M, Kelsen, S, Mamary, AJ, Marchetti, N, Satti, A, Shenoy, K, Steiner, RM, Swift, A, Swift, I, Vega-Sanchez, G, Dransfield, M, Wells, JM, Bhatt, S, Nath, H, Ramsdell, J, Soler, X, Yen, A, Cornellas, A, Newell, J, Thompson, B, Kazerooni, E, Martinez, F, Billings, J, and Allen, T
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respiratory tract diseases - Abstract
Copyright 2015 American Medical Association. All rights reserved. IMPORTANCE: Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free. OBJECTIVE: To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0. DESIGN, SETTING, AND PARTICIPANTS: Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n = 4388) (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity >0.7 and FEV1 >80% predicted) from the COPDGene study was compared with a GOLD 1 group (n = 794), COPD groups (n = 3690), and a group of never smokers (n = 108). Recruitment began in January 2008 and ended in July 2011. MAIN OUTCOMES AND MEASURES: Physical function impairments, respiratory symptoms, CT abnormalities, use of respiratory medications, and reduced respiratory-specific quality of life. RESULTS: One or more respiratory-related impairments were found in 54.1% (2375 of 4388) of the GOLD 0 group. The GOLD 0 group had worse quality of life (mean [SD] St George's Respiratory Questionnaire total score, 17.0 [18.0] vs 3.8 [6.8] for the never smokers; P
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- 2015
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9. Crystal structure of FTHFS2 from T.acetoxydans Re1
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Bergdahl, R., primary, Jacobson, F., additional, Muller, B., additional, Mikkelsen, N., additional, Schurer, A., additional, and Sandgren, M., additional
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- 2016
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10. Case Report: Fistulising fellows - diverticular and Crohn’s disease
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Viljoen, CA, Levin, DA, Roberts, R, Jacobson, F, and Thomson, SR
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A 62 year old female was diagnosed with Crohn’s colitis and complex perianal disease, in April 2010. Colonic involvement to the splenic flexure was confirmed on endoscopy and subsequent colonic biopsies demonstrated active non-necrotising granulomatous inflammation. Sigmoid diverticulosis was noted on the index endoscopy, in addition to the index contrasted abdominal computerized tomography scan (CT). A perianal fistula and peri-natal cleft ulceration was confirmed during examination under anaesthesia and a seton was inserted through the fistulous tract. The initial therapeutic regimen included systemic and topical corticosteroids, in addition to concurrent oral Azathioprine. However, both Azathioprine and then 6-mercaptopruine, resulted in severe gastrointestinal side effects, necessitating a change to intramuscular Methotrexate at a dose of 25 mg weekly.1 This sequence of therapeutic setbacks resulted in poor overall control of the disease.
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- 2013
11. CT metrics of airway disease and emphysema in severe COPD
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Kim, WJ, Silverman, EK, Hoffman, E, Criner, GJ, Mosenifar, Z, Sciurba, FC, Make, BJ, Carey, V, San José Estépar, R, Diaz, A, Reilly, JJ, Martinez, FJ, Washko, GR, Fishman, AP, Bozzarello, BA, Al-Amin, A, Katz, M, Wheeler, C, Baker, E, Barnard, P, Cagle, P, Carter, J, Chatziioannou, S, Conejo-Gonzales, K, Dubose, K, Haddad, J, Hicks, D, Kleiman, N, Milburn-Barnes, M, Nguyen, C, Reardon, M, Reeves-Viets, J, Sax, S, Sharafkhaneh, A, Wilson, O, Young, C, Espada, R, Butanda, R, Ellisor, M, Fox, P, Hale, K, Hood, E, Jahn, A, Jhingran, S, King, K, Miller, C, Nizami, I, Officer, T, Ricketts, J, Rodarte, J, Teague, R, Williams, K, Reilly, J, Sugarbaker, D, Fanning, C, Body, S, Duffy, S, Formanek, V, Fuhlbrigge, A, Hartigan, P, Hooper, S, Hunsaker, A, Jacobson, F, Moy, M, Peterson, S, Russell, R, Saunders, D, Swanson, S, McKenna, R, Mohsenifar, Z, Geaga, C, Biring, M, Clark, S, Cutler, J, Frantz, R, Julien, P, Lewis, M, Minkoff-Rau, J, Yegyan, V, Joyner, M, De-Camp, M, Stoller, J, Meli, Y, Apostolakis, J, Atwell, D, Chapman, J, DeVilliers, P, Dweik, R, Kraenzler, E, Lann, R, Kurokawa, N, Marlow, S, McCarthy, K, McCreight, P, Mehta, A, Meziane, M, Minai, O, and Steiger, M
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respiratory system ,respiratory tract diseases - Abstract
Background: CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods: Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of -950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV1and percent predicted value of FEV1with CT scan measures of emphysema and airway disease. Results: In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT (r = -0.28, p = 0.0001) and SRWA (r = -0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV1% predicted (R = -0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = -5.2, p = 0.009; β = -2.6, p = 0.008, respectively) and %LAA-950 (β = -10.6, p = 0.03) with the postbronchodilator FEV1% predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions: Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema. © 2009 American College of Chest Physicians.
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- 2009
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12. Flavin Coenzyme Analogs as Probes of Flavoenzyme Reaction Mechanisms
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WALSH, C., primary, JACOBSON, F., additional, and RYERSON, C. C., additional
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- 1980
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13. Non-emphysematous chronic obstructive pulmonary disease is associated with diabetes mellitus
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Hersh, CP, Make, BJ, Lynch, DA, Barr, RG, Bowler, RP, Calverley, PMA, Castaldi, PJ, Cho, MH, Coxson, HO, DeMeo, DL, Foreman, MG, Han, MLK, Harshfield, BJ, Hokanson, JE, Lutz, S, Ramsdell, JW, Regan, EA, Rennard, SI, Schroeder, JD, Sciurba, FC, Steiner, RM, Tal-Singer, R, van Beek, EJR, Silverman, EK, Crapo, JD, Lantz, R, Stepp, L, Melanson, S, Beaty, T, Laird, N, Lange, C, Santorico, S, Hansel, N, McDonald, ML, Zhou, J, Mattheisen, M, Wan, E, Hardin, M, Hetmanski, J, Parker, M, Murray, T, Newell, J, Reilly, J, Judy, P, Hoffman, E, Estepar, RSJ, Ross, J, Al Qaisi, M, Zach, J, Kluiber, A, Sieren, J, Mann, T, Richert, D, McKenzie, A, Akhavan, J, Stinson, D, Jensen, R, Farzadegan, H, Meyerer, S, Chandan, S, Bragan, S, Everett, D, Williams, A, Wilson, C, Forssen, A, Powell, A, Piccoli, J, Sontag, M, Black-Shinn, J, Kinney, G, Curtis, J, Kazerooni, E, Hanania, N, Alapat, P, Bandi, V, Guntupalli, K, Guy, E, Mallampalli, A, Trinh, C, Atik, M, Al-Azzawi, H, Willis, M, Pinero, S, Fahr, L, Nachiappan, A, Bray, C, Frigini, LA, Farinas, C, Katz, D, Freytes, J, Marciel, AM, Washko, G, Jacobson, F, Hatabu, H, Clarke, P, Gill, R, Hunsaker, A, Trotman-Dickenson, B, Madan, R, Thomashow, B, Hersh, CP, Make, BJ, Lynch, DA, Barr, RG, Bowler, RP, Calverley, PMA, Castaldi, PJ, Cho, MH, Coxson, HO, DeMeo, DL, Foreman, MG, Han, MLK, Harshfield, BJ, Hokanson, JE, Lutz, S, Ramsdell, JW, Regan, EA, Rennard, SI, Schroeder, JD, Sciurba, FC, Steiner, RM, Tal-Singer, R, van Beek, EJR, Silverman, EK, Crapo, JD, Lantz, R, Stepp, L, Melanson, S, Beaty, T, Laird, N, Lange, C, Santorico, S, Hansel, N, McDonald, ML, Zhou, J, Mattheisen, M, Wan, E, Hardin, M, Hetmanski, J, Parker, M, Murray, T, Newell, J, Reilly, J, Judy, P, Hoffman, E, Estepar, RSJ, Ross, J, Al Qaisi, M, Zach, J, Kluiber, A, Sieren, J, Mann, T, Richert, D, McKenzie, A, Akhavan, J, Stinson, D, Jensen, R, Farzadegan, H, Meyerer, S, Chandan, S, Bragan, S, Everett, D, Williams, A, Wilson, C, Forssen, A, Powell, A, Piccoli, J, Sontag, M, Black-Shinn, J, Kinney, G, Curtis, J, Kazerooni, E, Hanania, N, Alapat, P, Bandi, V, Guntupalli, K, Guy, E, Mallampalli, A, Trinh, C, Atik, M, Al-Azzawi, H, Willis, M, Pinero, S, Fahr, L, Nachiappan, A, Bray, C, Frigini, LA, Farinas, C, Katz, D, Freytes, J, Marciel, AM, Washko, G, Jacobson, F, Hatabu, H, Clarke, P, Gill, R, Hunsaker, A, Trotman-Dickenson, B, Madan, R, and Thomashow, B
- Abstract
Background: Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers. The utility of these clinical subtypes is unclear. However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant. The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients. Methods: Current and former smokers from the Genetic Epidemiology of COPD Study (COPDGene) had chest computed tomography (CT) scans with quantitative image analysis. Emphysema-predominant COPD was defined by low attenuation area at -950 Hounsfield Units (LAA-950) ≥10%. Non-emphysematous COPD was defined by airflow obstruction with minimal to no emphysema (LAA-950 < 5%). Results: Out of 4197 COPD subjects, 1687 were classified as emphysema-predominant and 1817 as non-emphysematous; 693 had LAA-950 between 5-10% and were not categorized. Subjects with emphysema-predominant COPD were older (65.6 vs 60.6 years, p < 0.0001) with more severe COPD based on airflow obstruction (FEV1 44.5 vs 68.4%, p < 0.0001), greater exercise limitation (6-minute walk distance 1138 vs 1331 ft, p < 0.0001) and reduced quality of life (St. George's Respiratory Questionnaire score 43 vs 31, p < 0.0001). Self-reported diabetes was more frequent in non-emphysematous COPD (OR 2.13, p < 0.001), which was also confirmed using a strict definition of diabetes based on medication use. The association between diabetes and non-emphysematous COPD was replicated in the ECLIPSE study. Conclusions: Non-emphysematous COPD, defined by airflow obstruction with a paucity of emphysema on chest CT scan, is associated with an increased risk of diabetes. COPD patients without emphysema may warrant closer monitoring for diabetes, hypertension, and hyperlipidemia and vice versa.
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- 2014
14. Arthritis and back pain impact respiratory-specific quality of life measures in smokers with and without COPD
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Regan, E.A., primary, Kinney, G.L., additional, Black-Shinn, J., additional, McDonald, M-L., additional, Jacobson, F., additional, Make, B., additional, Hokanson, J., additional, Silverman, E., additional, and Crapo, J.D., additional
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- 2014
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15. Scanners and drillers: Characterizing expert visual search through volumetric images
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Drew, T., primary, Vo, M. L.-H., additional, Olwal, A., additional, Jacobson, F., additional, Seltzer, S. E., additional, and Wolfe, J. M., additional
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- 2013
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16. pH dependence of copper geometry, reduction potential, and nitrite affinity in nitrite reductase.
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Jacobson, F., Pistorius, A.M.A., Farkas, D., Grip, W.J. de, Hansson, O., Sjolin, L., Neutze, R., Jacobson, F., Pistorius, A.M.A., Farkas, D., Grip, W.J. de, Hansson, O., Sjolin, L., and Neutze, R.
- Abstract
Contains fulltext : 52498.pdf (Publisher’s version ) (Open Access), Many properties of copper-containing nitrite reductase are pH-dependent, such as gene expression, enzyme activity, and substrate affinity. Here we use x-ray diffraction to investigate the structural basis for the pH dependence of activity and nitrite affinity by examining the type 2 copper site and its immediate surroundings in nitrite reductase from Rhodobacter sphaeroides 2.4.3. At active pH the geometry of the substrate-free oxidized type 2 copper site shows a near perfect tetrahedral geometry as defined by the positions of its ligands. At higher pH values the most favorable copper site geometry is altered toward a more distorted tetrahedral geometry whereby the solvent ligand adopts a position opposite to that of the His-131 ligand. This pH-dependent variation in type 2 copper site geometry is discussed in light of recent computational results. When co-crystallized with substrate, nitrite is seen to bind in a bidentate fashion with its two oxygen atoms ligating the type 2 copper, overlapping with the positions occupied by the solvent ligand in the high and low pH structures. Fourier transformation infrared spectroscopy is used to assign the pH dependence of the binding of nitrite to the active site, and EPR spectroscopy is used to characterize the pH dependence of the reduction potential of the type 2 copper site. Taken together, these spectroscopic and structural observations help to explain the pH dependence of nitrite reductase, highlighting the subtle relationship between copper site geometry, nitrite affinity, and enzyme activity.
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- 2007
17. Cellulose induced protein, Cip1
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Jacobson, F., primary, Karkehabadi, S., additional, Hansson, H., additional, Goedegebuur, F., additional, Wallace, L., additional, Mitchinson, C., additional, Piens, K., additional, Stals, I., additional, and Sandgren, M., additional
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- 2012
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18. Gallbladder herniation after minimally invasive cardiothoracic surgery
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Chick, J. F. B., primary, Sheehan, S. E., additional, and Jacobson, F., additional
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- 2012
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19. Identification of FGF7 as a novel susceptibility locus for chronic obstructive pulmonary disease
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Brehm, J. M., primary, Hagiwara, K., additional, Tesfaigzi, Y., additional, Bruse, S., additional, Mariani, T. J., additional, Bhattacharya, S., additional, Boutaoui, N., additional, Ziniti, J. P., additional, Soto-Quiros, M. E., additional, Avila, L., additional, Cho, M. H., additional, Himes, B., additional, Litonjua, A. A., additional, Jacobson, F., additional, Bakke, P., additional, Gulsvik, A., additional, Anderson, W. H., additional, Lomas, D. A., additional, Forno, E., additional, Datta, S., additional, Silverman, E. K., additional, and Celedon, J. C., additional
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- 2011
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20. Cerebral Palsy in Young Adults A Socio-Medical Study with Special Regard to Employment Problems
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Karlsson, Bengt, primary, Gardeström, L., additional, Nordqvist, I., additional, and Jacobson, F., additional
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- 2008
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21. Cu-containing nitrite reductase at pH 6.0 with bound nitrite
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Jacobson, F., primary
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- 2006
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22. Cu-containing nitrite reductase at pH 8.4 with bound nitrite
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Jacobson, F., primary
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- 2006
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23. Nitrite reductase pH 6.0
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Jacobson, F., primary
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- 2006
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24. Deformation of helix C in the low-temperature L-intermediate of bacteriorhodopsin
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Edman, K., primary, Royant, A., additional, Larsson, G., additional, Jacobson, F., additional, Taylor, T., additional, van der Spoel, D., additional, Landau, E.M., additional, Pebay-Peyroula, E., additional, and Neutze, R., additional
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- 2004
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25. Influence of CT image size and format on accuracy of lung nodule detection.
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Seltzer, S E, primary, Judy, P F, additional, Feldman, U, additional, Scarff, L, additional, and Jacobson, F L, additional
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- 1998
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26. Spiral CT of the chest: comparison of cine and film-based viewing.
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Seltzer, S E, primary, Judy, P F, additional, Adams, D F, additional, Jacobson, F L, additional, Stark, P, additional, Kikinis, R, additional, Swensson, R G, additional, Hooton, S, additional, Head, B, additional, and Feldman, U, additional
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- 1995
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27. Precision electrocautery excision of pulmonary lesions (Perelman technique): radiologic features.
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Stark, P, primary, Pugatch, R D, additional, DeCamp, M, additional, and Jacobson, F L, additional
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- 1993
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28. Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer.
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Krop IE, Beeram M, Modi S, Jones SF, Holden SN, Yu W, Girish S, Tibbitts J, Yi JH, Sliwkowski MX, Jacobson F, Lutzker SG, and Burris HA
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- 2010
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29. Personnel Management and the Law
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Jacobson, F.
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Human resource management ,Medical care ,Business ,Health care industry - Published
- 1983
30. Purification and properties of an 8-hydroxy-5-deazaflavin-reducing hydrogenase from Methanobacterium thermoautotrophicum.
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Jacobson, F S, Daniels, L, Fox, J A, Walsh, C T, and Orme-Johnson, W H
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A coenzyme F430-reducing hydrogenase from Methanobacterium thermoautotrophicum has been purified 25-fold, to approximately 50% homogeneity. Following anaerobic preincubation in high salt under reducing conditions, the purified enzyme exhibits equal catalytic activity (turnover number = 725 s-1) toward the artificial 1-electron acceptor, methyl viologen, and the physiological 2-electron acceptor, 7,8-didemethyl-8-hydroxy-5-deazaflavin (F420). The enzyme had the following Km values (micromolarity) under the described assay conditions: 420 (methyl viologen, pH 9.0), 19 (F420, pH 7.2), 34 (Fo, 7.8-didemethyl-8-hydroxy-5-deazariboflavin, pH 7.2), 10 (H2, Fo as co-substrate, pH 7.2), 2 (H2, methyl viologen as co-substrate, pH 9.0). The native protein is oligomeric (apparent Mr greater than 500,000) and is composed of three distinct subunits with Mr - 40,000, 31,000, and 26,000 in the ratio of 2:2:1, leading to a minimum Mr = 170,000. In addition to 33 atoms of Fe and 24 atoms of acid-labile sulfur, the F420-hydrogenase contains 2.3 mol of FAD/mol of Mr - 170,000. This activity is chromatographically distinct from a smaller methanogen hydrogenase capable of rapid viologen reduction, but which only very slowly reduces 5-deazariboflavins.
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- 1982
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31. Hydrogen peroxide-inducible proteins in Salmonella typhimurium overlap with heat shock and other stress proteins.
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Morgan, R W, Christman, M F, Jacobson, F S, Storz, G, and Ames, B N
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Hydrogen peroxide treatment induces the synthesis of 30 proteins in Salmonella typhimurium. Five of these proteins are also induced by heat shock, including the highly conserved DnaK protein. The induction of one of these five proteins by heat shock is dependent on oxyR, a positive regulator of hydrogen peroxide-inducible genes, while the induction of the other four by heat shock is oxyR independent. Five of the 30 hydrogen peroxide-inducible proteins have been identified, and their structural genes have been mapped. Other stresses such as nalidixic acid, ethanol, or cumene hydroperoxide treatment also induce subsets of the 30 hydrogen peroxide-inducible proteins as well as additional proteins. Hydrogen peroxide-inducible proteins are shown to be largely different from those proteins induced by aerobiosis. In addition, the expression of the katG (catalase) gene is shown to be regulated by oxyR at the level of mRNA.
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- 1986
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32. An Alkyl Hydroperoxide Reductase from Salmonella typhimuriumInvolved in the Defense of DNA against Oxidative Damage
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Jacobson, F S, Morgan, R W, Christman, M F, and Ames, B N
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A peroxide reductase (peroxidase) which converts lipid hydroperoxides and other alkyl hydroperoxides to the corresponding alcohols, using either NADH or NADPH as the reducing agent, has been identified in both Salmonella typhimuriumand Escherichia coli. This enzyme is shown to play a role in protecting against alkyl hydroperoxide mutagenesis. To our knowledge this work represents the first description of an NAD(P)H peroxidase in enteric bacteria and the first reported bacterial peroxidase to exhibit high activity toward alkyl hydroperoxides. A high performance liquid chromatography-based assay for the alkyl hydroperoxide reductase has been developed by monitoring the reduction of cumene hydroperoxide, a model alkyl hydroperoxide. By using this assay, the enzyme has been purified from a S. typhimuriumregulatory mutant, oxyR1, which overexpresses a number of proteins involved in defenses against oxidative damage, and which contains 20-fold more of the alkyl hydroperoxide reductase than the wild-type strain. The purified activity requires the presence of two separable components having subunit molecular weights of 22,000 and 57,000. The 57-kDa protein contains a bound FAD cofactor and can use either NADH or NADPH as an electron donor for the direct reduction of redox dyes, or of alkyl hydroperoxides when combined with the 22-kDa protein. This enzyme may thus serve as a prokaryotic equivalent to the glutathione reductase/glutathione peroxidase system in eukaryotes.
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- 1989
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33. An alkyl hydroperoxide reductase induced by oxidative stress in Salmonella typhimurium and Escherichia coli: genetic characterization and cloning of ahp
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Storz, G, Jacobson, F S, Tartaglia, L A, Morgan, R W, Silveira, L A, and Ames, B N
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The ahp genes encoding the two proteins (F52a and C22) that make up an alkyl hydroperoxide reductase were mapped and cloned from Salmonella typhimurium and Escherichia coli. Two classes of oxidant-resistant ahp mutants which overexpress the two proteins were isolated. ahp-1 was isolated in a wild-type background and is dependent on oxyR, a positive regulator of defenses against oxidative stress. ahp-2 was isolated in an oxyR deletion background and is oxyR independent. Transposons linked to ahp-1 and ahp-2 or inserted in ahp mapped the genes to 13 min on the S. typhimurium chromosome, 59% linked to ent. Deletions of ahp obtained in both S. typhimurium and E. coli resulted in hypersensitivity to killing by cumene hydroperoxide (an alkyl hydroperoxide) and elimination of the proteins F52a and C22 from two-dimensional gels and immunoblots. ahp clones isolated from both S. typhimurium and E. coli complemented the cumene hydroperoxide sensitivity of the ahp deletion strains and restored expression of the F52a and C22 proteins. A cis-acting element required for oxyR-dependent, rpoH-independent heat shock induction of the F52a protein was present at the S. typhimurium but not the E. coli ahp locus.
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- 1989
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34. Tracheobronchial cartilage calcifications in an inpatient population.
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Bravo, Stephen M., Stark, Paul, Jacobson, Francine, Bravo, S M, Stark, P, and Jacobson, F
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- 1995
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35. On antihydrogen formation in collisions of antiprotons with positronium
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Humberston, J W, primary, Charlton, M, additional, Jacobson, F M, additional, and Deutch, B I, additional
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- 1987
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36. HIV-associated lymphocytic interstitial pneumonia: radiologic manifestations and pathologic correlation.
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Oldham, S A, primary, Castillo, M, additional, Jacobson, F L, additional, Mones, J M, additional, and Saldana, M J, additional
- Published
- 1989
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37. ChemInform Abstract: SYNTHESIS OF 7,8-DIDEMETHYL-8-HYDROXY-5-DEAZARIBOFLAVIN AND CONFIRMATION OF ITS IDENTITY WITH THE DEAZAISOALLOXAZINE CHROMOPHORE OF METHANOBACTERIUM REDOX COENZYME F420
- Author
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ASHTON, W. T., primary, BROWN, R. D., additional, JACOBSON, F., additional, and WALSH, C., additional
- Published
- 1979
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38. An Alkyl Hydroperoxide Reductase from Salmonella typhimurium Involved in the Defense of DNA against Oxidative Damage
- Author
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Jacobson, F S, primary, Morgan, R W, additional, Christman, M F, additional, and Ames, B N, additional
- Published
- 1989
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39. Fistulising fellows - diverticular and Crohn's disease.
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Viljoe, C. A., Levin, D. A., Roberts, R., Jacobson, F., and Thomson, S. R.
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- *
ANAL disease diagnosis , *CROHN'S disease , *ABDOMINAL abnormality patients , *FEVER , *TACHYCARDIA , *ADALIMUMAB , *DISEASE risk factors - Abstract
The article presents a case study of a 62 year old female diagnosed with complex perianal disease and Crohn's colitis in April 2010. In July 2011, the patient's clinical examination revealed a pyrexia, tachycardia and marked suprapubic tenderness and the abdominal x-ray discovered faecal loading in transverse and ascending colon. The histology confirmed active chronic Crohn's colitis. The postoperative recovery was dull and adalimumab for induction and maintenance therapy was started up.
- Published
- 2012
40. Proteomic Profiles Associated With Postsurgical Progression in Nonfunctioning Pituitary Adenomas.
- Author
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Hallén T, Johannsson G, Thorsell A, Olsson DS, Örndal C, Engvall A, Jacobson F, Widgren A, Bergquist J, and Skoglund T
- Subjects
- Humans, Female, Male, Middle Aged, Adult, Case-Control Studies, Biomarkers, Tumor metabolism, Biomarkers, Tumor analysis, Neoplasm, Residual pathology, Aged, Proteome analysis, Proteome metabolism, Pituitary Neoplasms surgery, Pituitary Neoplasms metabolism, Pituitary Neoplasms pathology, Disease Progression, Proteomics, Adenoma surgery, Adenoma metabolism, Adenoma pathology
- Abstract
Context: There is a lack of reliable biomarkers capable of predicting postoperative tumor progression of nonfunctioning pituitary adenomas (NFPAs)., Objective: To discover proteomic profiles associated with postoperative tumor progression in patients with NFPAs. This was a case-controlled exploratory study at a tertiary university hospital. Tissue samples were obtained from 46 patients with residual tumor following surgery for NFPAs of gonadotroph lineage. Two patient groups were compared: patients requiring reintervention due to residual tumor progression (cases; reintervention group, n = 29) and patients with a residual tumor showing no progression for a minimum of 5 years (controls; radiologically stable group, n = 17). Differentially expressed proteins (DEPs) between patient groups were measured., Results: Global quantitative proteomic analysis identified 4074 proteins, of which 550 were differentially expressed between the 2 groups (fold change >80%, false discovery rate-adjusted P ≤ .05). Principal component analysis showed good separation between the 2 groups. Functional enrichment analysis of the DEPs indicated processes involving translation, ROBO-receptor signaling, energy metabolism, mRNA metabolism, and RNA splicing. Several upregulated proteins in the reintervention group, including SNRPD1, SRSF10, SWAP-70, and PSMB1, are associated with tumor progression in other cancer types., Conclusion: This is the first exploratory study analyzing proteomic profiles as markers of postoperative tumor progression in NFPAs. The findings clearly showed different profiles between tumors with indolent postoperative behavior and those with postoperative tumor progression. Both enriched pathways involving DEPs and specific upregulated proteins have previously been associated with tumor aggressiveness. These results suggest the value of proteomic profiling for predicting tumor progression in patients with NFPAs., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)
- Published
- 2024
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41. Adapting Behavioral Treatments for Primary Care Using a Theory-Based Framework: The Case of Adolescent Eating Disorders.
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Lebow J, Sim L, Redmond S, Billings M, Mattke A, Gewirtz O'Brien JR, Partain P, Narr C, Breland R, Soma D, Schmit T, Magill S, Leonard A, Crane S, Le Grange D, Loeb K, Clark M, Phelan S, Jacobson RM, Enders F, Lyster-Mensh LC, and Leppin A
- Subjects
- Humans, Adolescent, Child, Behavior Therapy, Mental Health, Primary Health Care, Feeding and Eating Disorders therapy, Mental Health Services
- Abstract
Evidence-based treatments have been developed for a range of pediatric mental health conditions. These interventions have proven efficacy but require trained pediatric behavioral health specialists for their administration. Unfortunately, the widespread shortage of behavioral health specialists leaves few referral options for primary care providers. As a result, primary care providers are frequently required to support young patients during their lengthy and often fruitless search for specialty treatment. One solution to this treatment-access gap is to draw from the example of integrated behavioral health and adapt brief evidence-based treatments for intra-disciplinary delivery by primary care providers in consultation with mental health providers. This solution has potential to expand access to evidence-based interventions and improve patient outcomes. We outline how an 8-step theory-based process for adapting evidence-based interventions, developed from a scoping review of the wide range of implementation science frameworks, can guide treatment development and implementation for pediatric behavioral health care delivery in the primary care setting, using an example of our innovative treatment adaptation for child and adolescent eating disorders. After reviewing the literature, obtaining input from leaders in eating disorder treatment research, and engaging community stakeholders, we adapted Family-Based Treatment for delivery in primary care. Pilot data suggest that the intervention is feasible to implement in primary care and preliminary findings suggest a large effect on adolescent weight gain. Our experience using this implementation framework provides a model for primary care providers looking to develop intra-disciplinary solutions for other areas where specialty services are insufficient to meet patient needs., Competing Interests: Declaration of Competing Interest Dr. Le Grange receives royalties from Guilford Press and Routledge. He also is Co-Director of the Training Institute for Child and Adolescent Eating Disorders, LLC. Dr. Loeb is also a faculty member at the Training Institute for Child and Adolescent Eating Disorders LLC. The other authors have indicated they have no financial relationships relevant to this article or potential conflicts of interest to disclose., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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42. Association of conduit dimensions with perioperative outcomes and long-term quality of life after esophagectomy for malignancy.
- Author
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Kim S, Lee SY, Vaz N, Leo R, Barcelos RR, Mototani R, Lozano A, Sugarbaker EA, Oh SS, Jacobson F, Wee JO, Jaklitsch MT, and Marshall MB
- Abstract
Objective: The impact of conduit dimensions and location of esophagogastric anastomosis on long-term quality of life after esophagectomy remains unexplored. We investigated the association of these parameters with surgical outcomes and patient-reported quality of life at least 18 months after esophagectomy., Methods: We identified all patients who underwent esophagectomy for cancer from 2018 to 2020 in our institution. We reviewed each patient's initial postoperative computed tomography scan measuring the gastric conduit's greatest width (centimeters), linear staple line length (centimeters), and relative location of esophagogastric anastomosis (vertebra). Quality of life was ascertained using patient-reported outcome measures. Perioperative complications, length of stay, and mortality were collected. Multivariate regressions were performed., Results: Our study revealed that a more proximal anastomosis was linked to an increased risk of pulmonary complications, a lower recurrence rate, and greater long-term insomnia. Increased maximum intrathoracic conduit width was significantly associated with trouble enjoying meals and reflux long term after esophagectomy. A longer conduit stapled line correlated with fewer issues related to insomnia, improved appetite, less dysphagia, and significantly enhanced "social," "role," and "physical'" aspects of the patient's long-term quality of life., Conclusions: The dimensions of the gastric conduit and the height of the anastomosis may be independently associated with outcomes and long-term quality of life after esophagectomy for cancer., Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2023 The Author(s).)
- Published
- 2023
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43. CMC Regulatory Considerations for Antibody-Drug Conjugates.
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Bechtold-Peters K, Ruggiero A, Vriezen N, Ihle N, Klein A, Morgan C, Schweizer D, Liu D, Jacobson F, Buecheler J, Panek M, Duggan N, Malyala P, Dupraz P, Desai P, Niu S, Feng Y, and Wang X
- Subjects
- Antibodies, Monoclonal chemistry, Immunoconjugates chemistry
- Abstract
Antibody-drug conjugates unite the specificity and long circulation time of an antibody with the toxicity of a chemical cytostatic or otherwise active drug using appropriate chemical linkers to reduce systemic toxicity and increase therapeutic index. This combination of a large biological molecule and a small molecule creates an increase in complexity. Multiple production processes are required to produce the native antibody, the drug and the linker, followed by conjugation of afore mentioned entities to form the final antibody-drug conjugate. The connected processes further increase the number of points of control, resulting in necessity of additional specifications and intensified analytical characterization. By combining scientific understanding of the production processes with risk-based approaches, quality can be demonstrated at those points where control is required and redundant comparability studies, specifications or product characterization are avoided. Over the product development lifecycle, this will allow process qualification to focus on those areas critical to quality and prevent redundant studies. The structure of the module 3 common technical document for an ADC needs to reflect each of the production processes and the combined overall approach to quality. Historically, regulatory authorities have provided varied expectations on its structure. This paper provides an overview of essential information to be included and shows that multiple approaches work as long as adequate cross-referencing is included., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)
- Published
- 2023
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- View/download PDF
44. Incidence of Clinically Relevant Solitary Pulmonary Nodules Utilizing a Universal Health Care System.
- Author
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Kuckelman J, Dezube A, Jacobson F, Learn PA, Miller D, Mody G, and Jaklitsch M
- Subjects
- Humans, Female, Adult, Incidence, Universal Health Care, Tomography, X-Ray Computed, Solitary Pulmonary Nodule epidemiology, Solitary Pulmonary Nodule diagnosis, Lung Neoplasms epidemiology, Lung Neoplasms diagnosis
- Abstract
Introduction: Solitary pulmonary nodules (SPNs) are common, but the clinical relevance of these nodules is unknown. Utilizing current screening guidelines, we sought to better characterize the national incidence of clinically important SPNs within the largest universal health care system in the nation., Materials and Methods: TRICARE data were queried to identify SPNs for ages 18-64 years. SPNs that had been diagnosed within a year with no prior oncologic history were included to ensure true incidence. A proprietary algorithm was applied to determine clinically significant nodules. Further analysis characterized incidence by age grouping, gender, region, military branch, and beneficiary status., Results: A total of 229,552 SPNs were identified with a 60% reduction seen after application of the clinical significance algorithm (N = 88,628). The incidence increased in each decade of life (all P < 0.01). Adjusted incident rate ratios were significantly higher for SPNs detected in the Midwest and Western regions. The incident rate ratio was also higher in females (1.05, confidence interval [CI] 1.018, P = 0.001) as well as non-active duty members (dependents = 1.4 and retired = 1.6, respectively, CIs 1.383-1.492 and 1.591-1.638, P < 0.01). The incidence calculated per 1,000 patients overall was 3.1/1,000. Ages 44-54 years had an incidence of 5.5/1,000 patients, which is higher than the previously reported incidence of < 5.0 nationally for the same age group., Conclusions: This analysis represents the largest evaluation of SPNs to date combined with clinical relevance adjustment. These data suggest a higher incidence of clinically significant SPNs starting at an age of 44 years in nonmilitary or retired women localized to the Midwest and Western regions of the United States., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
- Full Text
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45. Role of sex in lung cancer risk prediction based on single low-dose chest computed tomography.
- Author
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Simon J, Mikhael P, Tahir I, Graur A, Ringer S, Fata A, Jeffrey YC, Shepard JA, Jacobson F, Barzilay R, Sequist LV, Pace LE, and Fintelmann FJ
- Subjects
- Female, Humans, Male, Early Detection of Cancer methods, Artificial Intelligence, Tomography, X-Ray Computed methods, Risk, Lung Neoplasms diagnostic imaging, Lung Neoplasms epidemiology
- Abstract
A validated open-source deep-learning algorithm called Sybil can accurately predict long-term lung cancer risk from a single low-dose chest computed tomography (LDCT). However, Sybil was trained on a majority-male cohort. Use of artificial intelligence algorithms trained on imbalanced cohorts may lead to inequitable outcomes in real-world settings. We aimed to study whether Sybil predicts lung cancer risk equally regardless of sex. We analyzed 10,573 LDCTs from 6127 consecutive lung cancer screening participants across a health system between 2015 and 2021. Sybil achieved AUCs of 0.89 (95% CI: 0.85-0.93) for females and 0.89 (95% CI: 0.85-0.94) for males at 1 year, p = 0.92. At 6 years, the AUC was 0.87 (95% CI: 0.83-0.93) for females and 0.79 (95% CI: 0.72-0.86) for males, p = 0.01. In conclusion, Sybil can accurately predict future lung cancer risk in females and males in a real-world setting and performs better in females than in males for predicting 6-year lung cancer risk., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
46. Integrating tobacco treatment into lung cancer screening practices: Study protocol for the Screen ASSIST randomized clinical trial.
- Author
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Neil JM, Marotta C, Gonzalez I, Chang Y, Levy DE, Wint A, Harris K, Hawari S, Noonan E, Styklunas G, Crute S, Howard SE, Sheppard J, Lennes IT, Jacobson F, Flores EJ, Haas JS, Park ER, and Rigotti NA
- Subjects
- Early Detection of Cancer, Humans, Quality of Life, Randomized Controlled Trials as Topic, Tobacco Use Cessation Devices, Lung Neoplasms diagnosis, Smoking Cessation methods, Telemedicine, Tobacco Products
- Abstract
Background: Integrating tobacco treatment services into lung cancer screening (LCS) has the potential to leverage a 'teachable moment' to promote cessation among long-term smokers and reduce disparities in tobacco treatment access. This protocol paper describes the Screen ASSIST (Aiding Screening Support In Stopping Tobacco) trial, which will identify how to best deliver evidence-driven tobacco treatment in the context of LCS., Methods: Screen ASSIST is a randomized clinical trial with a 3-factor, fully crossed factorial design that enrolls current smokers (any cigarette use in the past 30 days) scheduled to attend LCS at multiple sites in the Mass General Brigham healthcare system. To maximize reach, recruitment is conducted at 3 time points: 1) at the time of LCS scheduling, 2) at the LCS visit, and 3) after the participant has received their LCS results. Participants are stratified by LCS study site and recruitment point and randomly assigned into 8 groups that test intervention components varying on telehealth counseling duration (4 weeks vs. 8 weeks), nicotine replacement therapy duration (2 weeks vs. 8 weeks), and systematic screening and referral for social determinants of health via a service named 'AuntBertha' (referral vs. no referral). The primary study outcome is self-reported past 7-day tobacco abstinence at 6-month follow-up. This trial will also assess systems integration and evaluate implementation of the intervention., Discussion: Screen ASSIST will identify the most effective combination of tobacco cessation treatments within the LCS context, in order to improve the cost-effectiveness of LCS and quality of life among long-term heavy smokers., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
- Full Text
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47. Development and evaluation of a telehealth-based simulation to improve breastfeeding education and skills among nursing students.
- Author
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Villegas N, Cianelli R, Cerisier K, Fernandez-Pineda M, Jacobson F, Lin HH, Sanchez H, Davenport E, and Zavislak K
- Subjects
- Breast Feeding, Cross-Sectional Studies, Curriculum, Female, Humans, Education, Nursing, Education, Nursing, Baccalaureate, Students, Nursing, Telemedicine
- Abstract
Aim: The aim of this study was to evaluate undergraduate nursing students' perceptions of using telehealth-based simulations for practicing their breastfeeding education skills., Background: Telehealth can help bridge the gap between the high need for healthcare services and the limited access to these services, such as breastfeeding mothers in rural settings. However current literature suggests that there is lack of telehealth education among healthcare providers, as well as, a shortage of adequately trained nurses on breastfeeding, making it difficult to provide new mothers with the support they need to successfully breastfeed. Telehealth simulation has shown to be acceptable and helpful in teaching clinical reasoning, increasing exposure to telehealth experiences, and preparing nursing students for real interaction experiences with patients., Design: For this cross-sectional descriptive study, two breastfeeding telehealth simulation scenarios were developed and delivered through Zoom for Bachelor of Science in Nursing students in a high-level institution in Florida. Selected students interacted over Zoom as healthcare providers with a female simulated patient who played as a mother with a breastfeeding concern. Students in their role of healthcare providers assessed the breastfeeding needs of the mother and conducted breastfeeding education as appropriate. After debriefing, students received feedback from faculty and students who observed the simulation and completed an optional evaluation about their telehealth simulated experience., Results: A total of 205 students completed the evaluation. Most students (n = 136, 66.3%) were not familiar with telehealth prior to the simulation. Most students (n = 199, 97.1%) also found the simulation helpful for supporting breastfeeding mothers and wanted more telehealth simulations in the future (n = 162, 79%). Feedback for improving the simulations included: improving the technical setup (n = 17, 8.3%), increasing the time that students interacted with the mother (n = 16, 7.8%), and observing the correct performance of the simulation after debriefing (n = 16, 7.8%)., Conclusion: Telehealth simulation is a promising modality for clinical competency assessment, thus it is essential to integrate telehealth education into nursing curriculum. It is evident that telehealth-based breastfeeding simulations can be used to address the exposure/knowledge gap among nursing students who are missing or have limited exposure to breastfeeding content and telehealth use in their nursing curriculum., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
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48. Exploring Intimate Partner Relationships before and after HIV Diagnosis among Minority Older Women.
- Author
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Villegas N, Cianelli R, De Oliveira G, Toledo C, Jacobson F, Davenport E, Webb D, and Wolf B
- Subjects
- Aged, Female, Humans, Interpersonal Relations, Qualitative Research, Sexual Behavior, HIV Infections diagnosis, Sexual Partners
- Abstract
Objectives: Literature shows that sexual activity remains important at older age and is a valued part of life. However, little is known about the intimate partner relationships (IPR) among minority older women living with Human Immunodeficiency Virus (HIV). The purpose of this study is to explore the effect HIV diagnosis had on the intimate partner relationships (IPR) among minority older women living with HIV (MOWH)., Methods: Qualitative descriptive study. A total of 28 MOWH (Black and Latinas) aged 50 years and older participated in face to face semi-structured in-depth interviews. Interviews were analyzed using content analysis., Results: Three themes emerged from the analysis: (a)" Intimate partner relationships before HIV diagnosis" that revealed sexual practices increasing the risk for HIV in their intimate relationships; (b)" Facing relationship consequences of HIV disclosure after diagnosis" explored the consequences of HIV disclosure, and how disclosure determined the future of their intimate relationships; and (c) "Intimate partner relationships after HIV diagnosis" described the quality of intimate partner relationships and changes after HIV diagnosis., Conclusions: Results from this study contribute to understanding and increasing awareness of the effect of HIV on the intimacy of MOWH., Clinical Implications: Education provided by health care workers and interventions targeting MOWH should address the effect of HIV in IPR, address MOWH's concerns about it, and help them to improve their overall health.
- Published
- 2021
- Full Text
- View/download PDF
49. Long-Term Radiologic Evaluation of Microaspirations among Patients after Esophagectomy.
- Author
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Pines G, Jacobson F, Zheng Y, Magali P, Lerut T, and Bueno R
- Subjects
- Aged, Anastomotic Leak etiology, Anastomotic Leak physiopathology, Deglutition, Esophagectomy instrumentation, Esophagus diagnostic imaging, Esophagus physiopathology, Female, Humans, Male, Middle Aged, Positron Emission Tomography Computed Tomography, Predictive Value of Tests, Respiratory Aspiration of Gastric Contents etiology, Respiratory Aspiration of Gastric Contents physiopathology, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Anastomotic Leak diagnostic imaging, Esophagectomy adverse effects, Esophagus surgery, Respiratory Aspiration of Gastric Contents diagnostic imaging, Tomography, X-Ray Computed
- Abstract
Objectives: Aspirations are common after esophagectomy. Data are lacking regarding its long-term radiological manifestations. The purpose of this study is to determine the incidence and radiological patterns of aspirations among long-term survivors and evaluate their clinical significance., Methods: The records of all patients who underwent esophagectomy between October 2003 and December 2011 and survived more than 3 years were reviewed. Preoperative, first routine postoperative, and latest chest computed tomography (CT)scans were reviewed. Imaging studies were reviewed for radiological signs suspicious of aspirations, conduit location, anastomotic site, and maximal intrathoracic diameter. Data regarding patients' complaints during clinic visits were also collected., Results: A total of 578 patients underwent esophagectomy during the study period. One-hundred twenty patients met the inclusion criteria. Median follow-up was 83.5 months. Cervical and intrathoracic anastomoses were performed in 103 and 17 patients, respectively. A higher rate of CT findings was found in postoperative imaging ( n = 51 [42.5%] vs. n = 13 [10.8%] respectively, p < 0.05). Most of these were found in the lower lobes (61%). A higher rate of lesions was found among patients in whom the conduit was bulging to the right hemithorax compared with totally mediastinal or completely in the right hemithorax (54.5 vs. 35.2% and 34.6%, respectively, p < 0.05). No correlation was found with conduit diameter or anastomotic site. These lesions were more prevalent among patients who complained of reflux or cough during meals (NS)., Conclusions: A significantly higher rate of new CT findings was found in postoperative imaging of this post-esophagectomy cohort, suggesting a high incidence of aspirations. The locations of the conduit, rather than anastomosis site, seem to play a role in the development of these findings. Further research is needed to evaluate the clinical significance of these findings., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme. All rights reserved.)
- Published
- 2021
- Full Text
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50. Streamlined Characterization of an Antibody-Drug Conjugate by Two-Dimensional and Four-Dimensional Liquid Chromatography/Mass Spectrometry.
- Author
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Goyon A, Kim M, Dai L, Cornell C, Jacobson F, Guillarme D, and Stella C
- Subjects
- Antibodies chemistry, Cysteine chemistry, Hydrogen-Ion Concentration, Hydrophobic and Hydrophilic Interactions, Immunoconjugates chemistry, Light, Oxidation-Reduction, Peptide Mapping, Proteolysis, Solutions, Trypsin chemistry, Antibodies analysis, Chromatography, High Pressure Liquid standards, Immunoconjugates analysis, Peptide Fragments analysis
- Abstract
This study describes the use of a multidimensional HPLC (2D and 4D) system for a faster and more effective characterization of an antibody-drug conjugate (ADC) product, compared to the standard off-line approach of fraction collection and off-line variant characterization. The size variants of an interchain cysteine-linked ADC were characterized to understand the effect of the different drug-to-antibody ratio (DAR) species on aggregate formation. For this purpose, the ADC product and a full panel of stressed samples were analyzed. The dimeric ADC species were baseline resolved from the main peak (Rs = 2.7) by UHP-SEC (ultra-high-performance size exclusion chromatography) under nondenaturing conditions using a buffered mobile phase containing 5% 2-propanol. A 2D-LC (SEC-HIC) method was then developed to compare the average DAR values of the main peak species vs the aggregates. A 4D-LC/MS method (SEC-reduction-digestion-RPHPLC) was also developed to determine levels of potential critical quality attributes (pCQAs) including aggregation, average DAR, oxidation, and deamidation, in a 2 h run. An average DAR value of 3.5-3.6 was found for the main peak using both 2D-LC and 4D-LC methods, and these values were consistent with DAR determined by the in-house reference hydrophobic interaction chromatography (HIC) method. The multidimensional LC approaches also showed an increase in the content of high-DAR species in the SEC fractions containing the aggregates. Overall the entire workflow of data acquisition is completed within a day using the multidimensional on-line approach, in comparison to multiple days required with the traditional off-line approaches.
- Published
- 2019
- Full Text
- View/download PDF
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