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5. Human-Induced Pluripotent Stem Cell (iPSC)-Derived GABAergic Neuron Differentiation in Bipolar Disorder.

Author

Schill, Daniel J., Attili, Durga, DeLong, Cynthia J., McInnis, Melvin G., Johnson, Craig N., Murphy, Geoffrey G., and O'Shea, K. Sue

Subjects
INDUCED pluripotent stem cells, GABAERGIC neurons, PLURIPOTENT stem cells, GABA, STEM cells, INTERNEURONS, CHLORIDE channels
Abstract

Bipolar disorder (BP) is a recurring psychiatric condition characterized by alternating episodes of low energy (depressions) followed by manias (high energy). Cortical network activity produced by GABAergic interneurons may be critical in maintaining the balance in excitatory/inhibitory activity in the brain during development. Initially, GABAergic signaling is excitatory; with maturation, these cells undergo a functional switch that converts GABAA channels from depolarizing (excitatory) to hyperpolarizing (inhibitory), which is controlled by the intracellular concentration of two chloride transporters. The earliest, NKCC1, promotes chloride entry into the cell and depolarization, while the second (KCC2) stimulates movement of chloride from the neuron, hyperpolarizing it. Perturbations in the timing or expression of NKCC1/KCC2 may affect essential morphogenetic events including cell proliferation, migration, synaptogenesis and plasticity, and thereby the structure and function of the cortex. We derived induced pluripotent stem cells (iPSC) from BP patients and undiagnosed control (C) individuals, then modified a differentiation protocol to form GABAergic interneurons, harvesting cells at sequential stages of differentiation. qRT-PCR and RNA sequencing indicated that after six weeks of differentiation, controls transiently expressed high levels of NKCC1. Using multi-electrode array (MEA) analysis, we observed that BP neurons exhibit increased firing, network bursting and decreased synchrony compared to C. Understanding GABA signaling in differentiation may identify novel approaches and new targets for treatment of neuropsychiatric disorders such as BP. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Cohort Profile Update: The Heinz C. Prechter Longitudinal Study of Bipolar Disorder

Author

Yocum, Anastasia K, primary, Anderau, Steve, additional, Bertram, Holli, additional, Burgess, Helen J, additional, Cochran, Amy L, additional, Deldin, Patricia J, additional, Evans, Simon J, additional, Han, Peisong, additional, Jenkins, Paul M, additional, Kaur, Ravleen, additional, Langenecker, Scott A, additional, Marshall, David F, additional, Mower Provost, Emily, additional, Sue O’Shea, K, additional, Ryan, Kelly A, additional, Sperry, Sarah H, additional, Smith, Shawna N, additional, Tso, Ivy F, additional, Versha, Kritika M, additional, Wright, Brittany M, additional, Zöllner, Sebastian, additional, and McInnis, Melvin G, additional

Published
2023
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21. Chlorhexidine versus povidone–iodine skin antisepsis before upper limb surgery (CIPHUR) : an international multicentre prospective cohort study

Author

Wade, Ryckie G., Bourke, Gráinne, Wormald, Justin C. R., Totty, Joshua Philip, Stanley, Guy Henry Morton, Lewandowski, Andrew, Rakhra, Sandeep Singh, Gardiner, Matthew D., Bindra, R., Sher, M., Thomas, M., Morgan, S. D. J., Hwang, B., Santucci, W., Tran, P., Kopp, L., Kunc, V., Hamdi, A., Grieve, P. P., Mukhaizeem, S. A., Blake, K., Cuggy, C., Dolan, R., Downes, E., Geary, E., Ghadge, A., Gorman, P., Jonson, M., Jumper, N., Kelly, S., Leddy, L., McMahon, M. E., McNamee, C., Miller, P., Murphy, B., O'Halloran, L., O’Shea, K., Skeens, J., Staunton, S., Timon, F., Woods, J., Cortinovis, U., Sala, L., Zingarello, V., Jusoh, M. H., Sadagatullah, A. N., Georgieva, G., Pejkova, S., Nikolovska, B., Srbov, B., Hamid, H. K. S., Mustafa, M., Abdelrahman, M., Amin, S. M. M., Bhatti, D., Rahman, K. M. A., Jumabhoy, I., Kiely, J., Kieran, I., Lo, A. C. Q., Wong, K Y., Allan, A. Y., Armes, H., Horwitz, M. D., Ioannidi, L., Masterton, G., Chu, H., Talawadekar, G. D., Tong, K. S., Chan, M., Tredgett, M., Hardie, C., Powell-Smith, E., Gilham, N., Prokopenko, M., Ahmad, R., Davies, J., Zhen, S., Dargan, D., Pinder, R. M., Koziara, M., Martin, R., Reay, E., Cochrane, E., Elbatawy, A., Green, F., Griffiths, T., Higginbotham, G., Louette, S., McCauley, G., Natalwala, I., Salt, E., Ahmed, R., Goon, P., Manton, R., Segaren, N., Cheung, G., Mahoney, R., Sen, S., Clarkson, D., Collins, M., Bolt, A., Lokanathan, P., Ng, A., Jones, G., Jones, J. W. M., Kabariti, R., Rhee, S. J., Herron, J., Kay, A., Cheung, L. K., Thomson, D., Jugdey, R. S., Yoon, H., L, Z., Southgate, J., Brennan, C., Kiani, S., Zabaglo, M., Haider, Z. A., Poulter, R., Sheik-Ali, A., Watts, A., Jemec, B., Redgrave, N., Dupley, L., Greenhalgh, M., Vella, J., Harris, H., Robinson, A. V., Dupre, S., Teelucksingh, S., Gargan, A., Hettiaratchy, S., Jain, A., Kwasnicki, R., Lee, A., Thakkar, M., Berwick, D., Ismail, N., Mahdi, M., Rodrigues, Jeremy, Liew, C., Saadya, A., Clarkson, M., Brady, C., Harrison, R., Rayner, A., Nolan, G., Phillips, B., Madhusudan, N., and HASH(0x5651c97f7e70)

Subjects
Adult, AcademicSubjects/MED00910, Chlorhexidine, Bjs/2, Antisepsis, General Medicine, Upper Extremity, Preoperative Care, Humans, Original Article, Prospective Studies, AcademicSubjects/MED00010, Child, Povidone-Iodine, RA, RD
Abstract

Introduction Surgical site infection (SSI) is the most common and costly complication of surgery. International guidelines recommend topical alcoholic chlorhexidine (CHX) before surgery. However, upper limb surgeons continue to use other antiseptics, citing a lack of applicable evidence, and concerns related to open wounds and tourniquets. This study aimed to evaluate the safety and effectiveness of different topical antiseptics before upper limb surgery. Methods This international multicentre prospective cohort study recruited consecutive adults and children who underwent surgery distal to the shoulder joint. The intervention was use of CHX or povidone–iodine (PVI) antiseptics in either aqueous or alcoholic form. The primary outcome was SSI within 90 days. Mixed-effects time-to-event models were used to estimate the risk (hazard ratio (HR)) of SSI for patients undergoing elective and emergency upper limb surgery. Results A total of 2454 patients were included. The overall risk of SSI was 3.5 per cent. For elective upper limb surgery (1018 patients), alcoholic CHX appeared to be the most effective antiseptic, reducing the risk of SSI by 70 per cent (adjusted HR 0.30, 95 per cent c.i. 0.11 to 0.84), when compared with aqueous PVI. Concerning emergency upper limb surgery (1436 patients), aqueous PVI appeared to be the least effective antiseptic for preventing SSI; however, there was uncertainty in the estimates. No adverse events were reported. Conclusion The findings align with the global evidence base and international guidance, suggesting that alcoholic CHX should be used for skin antisepsis before clean (elective upper limb) surgery. For emergency (contaminated or dirty) upper limb surgery, the findings of this study were unclear and contradict the available evidence, concluding that further research is necessary., This international study recruited 2454 children and adults undergoing surgery on their upper limb (arm or hand), from 42 hospitals worldwide. The overall risk of infection after surgery was 3.5 per cent. Before planned (elective) surgery, if surgeons cleaned the skin with alcoholic chlorhexidine, then the risk of infection was reduced by 70 per cent.

Published
2021

23. Predicting the difficult laparoscopic cholecystectomy: development and validation of a pre-operative risk score using an objective operative difficulty grading system

Author

Nassar, A. H. M., Hodson, J., H. J., Ng, Vohra, R. S., Katbeh, T., Zino, S., Griffiths, E. A., Kirkham, A. J., Pasquali, S., Marriott, P., Johnstone, M., Spreadborough, P., Alderson, D., Fenwick, S., Elmasry, M., Nunes, Q. M., Kennedy, D., Khan, R. B., Khan, M. A. S., Magee, C. J., Jones, S. M., Mason, D., Parappally, C. P., Mathur, P., Saunders, M., Jamel, S., Haque, S. U., Zafar, S., Shiwani, M. H., Samuel, N., Dar, F., Jackson, A., Lovett, B., Dindyal, S., Winter, H., Fletcher, T., Rahman, S., Wheatley, K., Nieto, T., Ayaani, S., Youssef, H., Nijjar, R. S., Watkin, H., Naumann, D., Emesih, S., Sarmah, P. B., Lee, K., Joji, N., Lambert, J., Heath, J., Teasdale, R. L., Weerasinghe, C., Needham, P. J., Welbourn, H., Forster, L., Finch, D., Blazeby, J. M., Robb, W., Mcnair, A. G. K., Hrycaiczuk, A., Charalabopoulos, A., Kadirkamanathan, S., Tang, C. -B., Jayanthi, N. V. G., Noor, N., Dobbins, B., Cockbain, A. J., Nilsen-Nunn, A., de Siqueira, J., Pellen, M., Cowley, J. B., W. -M., Ho, Miu, V., White, T. J., Hodgkins, K. A., Kinghorn, A., Tutton, M. G., Al-Abed, Y. A., Menzies, D., Ahmad, A., Reed, J., Khan, S., Monk, D., Vitone, L. J., Murtaza, G., Joel, A., Brennan, S., Shier, D., Zhang, C., Yoganathan, T., Robinson, S. J., Mccallum, I. J. D., Jones, M. J., Elsayed, M., Tuck, L., Wayman, J., Carney, K., Aroori, S., Hosie, K. B., Kimble, A., Bunting, D. M., Fawole, A. S., Basheer, M., Dave, R. V., Sarveswaran, J., Jones, E., Kendal, C., Tilston, M. P., Gough, M., Wallace, T., Singh, S., Mockford, J. D. K. A., Issa, E., Shah, N., Chauhan, N., Wilson, T. R., Forouzanfar, A., Wild, J. R. L., Nofal, E., Bunnell, C., Madbak, K., Rao, S. T. V., Devoto, L., Siddiqi, N., Khawaja, Z., Hewes, J. C., Gould, L., Chambers, A., Rodriguez, D. U., Sen, G., Robinson, S., Bartlett, F., Rae, D. M., Stevenson, T. E. J., Sarvananthan, K., Dwerryhouse, S. J., Higgs, S. M., Old, O. J., Hardy, T. J., Shah, R., Hornby, S. T., Keogh, K., Frank, L., Al-Akash, M., Upchurch, E. A., Frame, R. J., Hughes, M., Jelley, C., Weaver, S., Roy, S., Sillo, T. O., Galanopoulos, G., Cuming, T., Cunha, P., Tayeh, S., Kaptanis, S., Heshaishi, M., Eisawi, A., Abayomi, M., Ngu, W. S., Fleming, K., Bajwa, D. S., Chitre, V., Aryal, K., Ferris, P., Silva, M., Lammy, S., Mohamed, S., Khawaja, A., Hussain, A., Ghazanfar, M. A., Bellini, M. I., Ebdewi, H., Elshaer, M., Gravante, G., Drake, B., Ogedegbe, A., Mukherjee, D., Arhi, C., Giwa, L., Iqbal, N., Watson, N. F., Aggarwal, S. K., Orchard, P., Villatoro, E., Willson, P. D., Mok, K. W. J., Woodman, T., Deguara, J., Garcea, G., Babu, B. I., Dennison, A. R., Malde, D., Lloyd, D., Satheesan, S., Al-Taan, O., Boddy, A., Slavin, J. P., Jones, R. P., Ballance, L., Gerakopoulos, S., Jambulingam, P., Mansour, S., Sakai, N., Acharya, V., Sadat, M. M., Karim, L., Larkin, D., Amin, K., Khan, A., Law, J., Jamdar, S., Smith, S. R., Sampat, K., O'Shea, K. M., Manu, M., Asprou, F. M., Malik, N. S., Chang, J., Lewis, M., Roberts, G. P., Karavadra, B., Photi, E., Hewes, J., Rodriguez, D., O'Reilly, D. A., Rate, A. J., Sekhar, H., Henderson, L. T., Starmer, B. Z., Coe, P. O., Tolofari, S., Barrie, J., Bashir, G., Sloane, J., Madanipour, S., Halkias, C., Trevatt, A. E. J., Borowski, D. W., Hornsby, J., Courtney, M. J., Virupaksha, S., Seymour, K., Hawkins, H., Bawa, S., Gallagher, P. V., Reid, A., Wood, P., Finch, J. G., Guy Finch, J., Parmar, J., Stirland, E., Gardner-Thorpe, J., Al-Muhktar, A., Peterson, M., Majeed, A., Bajwa, F. M., Martin, J., Choy, A., Tsang, A., Pore, N., Andrew, D. R., Al-Khyatt, W., Taylor, C., Bhandari, S., Subramanium, D., Toh, S. K. C., Carter, N. C., Tate, S., Pearce, B., Wainwright, D., Mercer, S. J., Knight, B., Vijay, V., Alagaratnam, S., Sinha, S., El-Hasani, S. S., Hussain, A. A., Bhattacharya, V., Kansal, N., Fasih, T., Jackson, C., Siddiqui, M. N., Chishti, I. A., Fordham, I. J., Siddiqui, Z., Bausbacher, H., Geogloma, I., Gurung, K., Tsavellas, G., Basynat, P., Shrestha, A. K., Basu, S., Chhabra, A., Harilingam, M., Rabie, M., Akhtar, M., Kumar, P., Jafferbhoy, S. F., Hussain, N., Raza, S., Haque, M., Alam, I., Aseem, R., Patel, S., Asad, M., Booth, M. I., Ball, W. R., Wood, C. P. J., Pinho-Gomes, A. C., Kausar, A., Obeidallah, M. R., Varghase, J., Lodhia, J., Bradley, D., Rengifo, C., Lindsay, D., Gopalswamy, S., Finlay, I., Wardle, S., Bullen, N., Iftikhar, S. Y., Awan, A., Ahmed, J., Leeder, P., Fusai, G., Bond-Smith, G., Psica, A., Puri, Y., Hou, D., Noble, F., Szentpali, K., Broadhurst, J., Date, R., Hossack, M. R., Goh, Y. L., Turner, P., Shetty, V., Riera, M., Macano, C. A. W., Sukha, A., Preston, S. R., Hoban, J. R., Puntis, D. J., Williams, S. V., Krysztopik, R., Kynaston, J., Batt, J., Doe, M., Goscimski, A., Jones, G. H., Hall, C., Carty, N., Panteleimonitis, S., Gunasekera, R. T., Sheel, A. R. G., Lennon, H., Hindley, C., Reddy, M., Kenny, R., Elkheir, N., Mcglone, E. R., Rajaganeshan, R., Hancorn, K., Hargreaves, A., Prasad, R., Longbotham, D. A., Vijayanand, D., Wijetunga, I., Ziprin, P., Nicolay, C. R., Yeldham, G., Read, E., Gossage, J. A., Rolph, R. C., Ebied, H., Phull, M., Khan, M. A., Popplewell, M., Kyriakidis, D., Henley, N., Packer, J. R., Derbyshire, L., Porter, J., Appleton, S., Farouk, M., Basra, M., Jennings, N. A., Ali, S., Kanakala, V., Ali, H., Lane, R., Dickson-Lowe, R., Zarsadias, P., Mirza, D., Puig, S., Al Amari, K., Vijayan, D., Sutcliffe, R., Marudanayagam, R., Hamady, Z., Prasad, A. R., Patel, A., Durkin, D., Kaur, P., Bowen, L., Byrne, J. P., Pearson, K. L., Delisle, T. G., Davies, J., Tomlinson, M. A., Johnpulle, M. A., Slawinski, C., Macdonald, A., Nicholson, J., Newton, K., Mbuvi, J., Farooq, A., Mothe, B. S., Zafrani, Z., Brett, D., Francombe, J., Barnes, J., Cheung, M., Al-Bahrani, A. Z., Preziosi, G., Urbonas, T., Alberts, J., Mallik, M., Patel, K., Segaran, A., Doulias, T., Sufi, P. A., Yao, C., Pollock, S., Manzelli, A., Wajed, S., Kourkulos, M., Pezzuto, R., Wadley, M., Hamilton, E., Jaunoo, S., Padwick, R., Sayegh, M., Newton, R. C., Hebbar, M., Farag, S. F., Spearman, J., Hamdan, M. F., D'Costa, C., Blane, C., Giles, M., Peter, M. B., Hirst, N. A., Hossain, T., Pannu, A., El-Dhuwaib, Y., Morrison, T. E. M., Taylor, G. W., Thompson, R. L. E., Mccune, K., Loughlin, P., Lawther, R., Byrnes, C. K., Simpson, D. J., Mawhinney, A., Warren, C., Mckay, D., Mcilmunn, C., Martin, S., Macartney, M., Diamond, T., Davey, P., Jones, C., Clements, J. M., Digney, R., Chan, W. M., Mccain, S., Gull, S., Janeczko, A., Dorrian, E., Harris, A., Dawson, S., Johnston, D., Mcaree, B., Ghareeb, E., Thomas, G., Connelly, M., Mckenzie, S., Cieplucha, K., Spence, G., Campbell, W., Hooks, G., Bradley, N., Hill, A. D. K., Cassidy, J. T., Boland, M., Burke, P., Nally, D. M., Khogali, E., Shabo, W., Iskandar, E., Mcentee, G. P., O'Neill, M. A., Peirce, C., Lyons, E. M., O'Sullivan, A. W., Thakkar, R., Carroll, P., Ivanovski, I., Balfe, P., Lee, M., Winter, D. C., Kelly, M. E., Hoti, E., Maguire, D., Karunakaran, P., Geoghegan, J. G., Mcdermott, F., Martin, S. T., Cross, K. S., Cooke, F., Zeeshan, S., Murphy, J. O., Mealy, K., Mohan, H. M., Nedujchelyn, Y., Ullah, M. F., Ahmed, I., Giovinazzo, F., Milburn, J., Prince, S., Brooke, E., Buchan, J., Khalil, A. M., Vaughan, E. M., Ramage, M. I., Aldridge, R. C., Gibson, S., Nicholson, G. A., Vass, D. G., Grant, A. J., Holroyd, D. J., Jones, M. A., Sutton, C. M. L. R., O'Dwyer, P., Nilsson, F., Weber, B., Williamson, T. K., Lalla, K., Bryant, A., Carter, C. R., Forrest, C. R., Hunter, D. I., Nassar, A. H., Orizu, M. N., Knight, K., Qandeel, H., Suttie, S., Belding, R., Mcclarey, A., Boyd, A. T., Guthrie, G. J. K., Lim, P. J., Luhmann, A., Watson, A. J. M., Richards, C. H., Nicol, L., Madurska, M., Harrison, E., Boyce, K. M., Roebuck, A., Ferguson, G., Pati, P., Wilson, M. S. J., Dalgaty, F., Fothergill, L., Driscoll, P. J., Mozolowski, K. L., Banwell, V., Bennett, S. P., Rogers, P. N., Skelly, B. L., Rutherford, C. L., Mirza, A. K., Lazim, T., Lim, H. C. C., Duke, D., Ahmed, T., Beasley, W. D., Wilkinson, M. D., Maharaj, G., Malcolm, C., Brown, T. H., Al-Sarireh, B., Shingler, G. M., Mowbray, N., Radwan, R., Morcous, P., Wood, S., Kadhim, A., Stewart, D. J., Baker, A. L., Tanner, N., Shenoy, H., Hafiz, S., De Marchi, J. A., Singh-Ranger, D., Hisham, E., Ainley, P., O'Neill, S., Terrace, J., Napetti, S., Hopwood, B., Rhys, T., Downing, J., Kanavati, O., Coats, M., Aleksandrov, D., Kallaway, C., Yahya, S., Templeton, A., Trotter, M., Lo, C., Dhillon, A., Heywood, N., Aawsaj, Y., Hamdan, A., Reece-Bolton, O., Mcguigan, A., Shahin, Y., Aymon, Luther, A. A., Nicholson, J. A., Rajendran, I., Boal, M., and Ritchie, J.

Subjects
Adult, Male, operative difficulty, medicine.medical_specialty, medicine.medical_treatment, Difficulty grading, difficult cholecystectomy, predictive score, surgery, laparoscopic, cholecystectomy, Surgical planning, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Preoperative Care, Humans, Medicine, Laparoscopic cholecystectomy, Framingham Risk Score, business.industry, General surgery, Reproducibility of Results, Middle Aged, medicine.disease, Pre operative, Single surgeon, Cholecystectomy, Laparoscopic, ROC Curve, 030220 oncology & carcinogenesis, Multivariate Analysis, Cholecystitis, Female, 030211 gastroenterology & hepatology, Surgery, Cholecystectomy, business, Abdominal surgery
Abstract

The prediction of a difficult cholecystectomy has traditionally been based on certain pre-operative clinical and imaging factors. Most of the previous literature reported small patient cohorts and have not used an objective measure of operative difficulty. The aim of this study was to develop a pre-operative score to predict difficult cholecystectomy, as defined by a validated intra-operative difficulty grading scale. Two cohorts from prospectively maintained databases of patients who underwent laparoscopic cholecystectomy were analysed: the CholeS Study (8755 patients) and a single surgeon series (4089 patients). Factors potentially predictive of difficulty were correlated to the Nassar intra-operative difficulty scale. A multivariable binary logistic regression analysis was then used to identify factors that were independently associated with difficult laparoscopic cholecystectomy, defined as operative difficulty grades 3 to 5. The resulting model was then converted to a risk score, and validated on both internal and external datasets. Increasing age and ASA classification, male gender, diagnosis of CBD stone or cholecystitis, thick-walled gallbladders, CBD dilation, use of pre-operative ERCP and non-elective operations were found to be significant independent predictors of difficult cases. A risk score based on these factors returned an area under the ROC curve of 0.789 (95% CI 0.773–0.806, p

Published
2019
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30. Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells

Author

Garcia-Perez, Jose L., Morell, Maria, Scheys, Joshua O., Kulpa, Deanna A., Morell, Santiago, Carter, Christoph C., Hammer, Gary D., Collins, Kathleen L., O'Shea, K. Sue, Menendez, Pablo, and Moran, John V.

Subjects
Retrotransposons -- Health aspects -- Genetic aspects -- Research, Gene silencing -- Research -- Health aspects -- Genetic aspects, Genetic engineering -- Research -- Health aspects -- Genetic aspects, Cancer -- Genetic aspects, Cancer cells -- Genetic aspects -- Health aspects -- Research
Abstract

Long interspersed element-1 (LINE-1 or L1) retrotransposition continues to affect human genome evolution (1,2). Lis can retrotranspose in the germline, during early development and in select somatic cells (3-8); however, the host response to L1 retrotransposition remains largely unexplored. Here we show that reporter genes introduced into the genome of various human embryonic carcinoma-derived cell lines (ECs) by L1 retrotransposition are rapidly and efficiently silenced either during or immediately after their integration. Treating ECs with histone deacetylase inhibitors rapidly reverses this silencing, and chromatin immunoprecipitation experiments revealed that reactivation of the reporter gene was correlated with changes in chromatin status at the L1 integration site. Under our assay conditions, rapid silencing was also observed when reporter genes were delivered into ECs by mouse L1s and a zebrafish LINE-2 element, but not when similar reporter genes were delivered into ECs by Moloney murine leukaemia virus or human immunodeficiency virus, suggesting that these integration events are silenced by distinct mechanisms. Finally, we demonstrate that subjecting ECs to culture conditions that promote differentiation attenuates the silencing of reporter genes delivered by L1 retrotransposition, but that differentiation, in itself, is not sufficient to reactivate previously silenced reporter genes. Thus, our data indicate that ECs differ from many differentiated cells in their ability to silence reporter genes delivered by L1 retrotransposition., Human ECs have a transcription profile similar to human embryonic stem cells, and have been used as a model of early human development (9). Previous studies demonstrated that human L1s [...]

Published
2010
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31. L1 retrotransposition in human neural progenitor cells

Author

Coufal, Nicole G., Garcia-Perez, Jose L., Peng, Grace E., Yeo, Gene W., Mu, Yangling, Lovci, Michael T., Morell, Maria, O'Shea, K. Sue, Moran, John V., and Gage, Fred H.

Subjects
DNA -- Research -- Physiological aspects, Nervous system -- Research -- Physiological aspects, Cell culture -- Research -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation, Physiological aspects, Research
Abstract

Long interspersed element 1 (LINE-1 or L1) retrotransposons have markedly affected the human genome. L1s must retrotranspose in the germ line or during early development to ensure their evolutionary success, yet the extent to which this process affects somatic cells is poorly understood. We previously demonstrated that engineered human L1s can retrotranspose in adult rat hippocampus progenitor cells in vitro and in the mouse brain in vivo (1). Here we demonstrate that neural progenitor cells isolated from human fetal brain and derived from human embryonic stem cells support the retrotransposition of engineered human L1s in vitro. Furthermore, we developed a quantitative multiplex polymerase chain reaction that detected an increase in the copy number of endogenous L1s in the hippocampus, and in several regions of adult human brains, when compared to the copy number of endogenous L1s in heart or liver genomic DNAs from the same donor. These data suggest that de novo L1 retrotransposition events may occur in the human brain and, in principle, have the potential to contribute to individual somatic mosaicism., The human nervous system is complex, containing approximately [10.sup.5] synapses with a vast diversity of neuronal cell types and connections that are influenced by complex and incompletely understood environmental and [...]

Published
2009

32. Same data, different conclusions: Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis

Author

Schweinsberg, M., Feldman, M., Staub, N., van den Akker, O.R., van Aert, R.C.M., van Assen, M.A.L.M., Liu, Y., Althoff, T., Heer, J., Kale, A., Mohamed, Z., Amireh, H., Venkatesh Prasad, V., Bernstein, A., Robinson, E., Snellman, K., Sommer, S.A., Otner, S.M.G., Robinson, D.A., Madan, N., Silberzahn, R., Goldstein, P., Tierney, W., Murase, T., Mandl, B., Viganola, D., Strobl, C., Schaumans, C.B.C., Kelchtermans, S., Naseeb, C., Mason Garrison, S., Yarkoni, T., Richard Chan, C. S., Adie, P., Alaburda, P., Albers, C., Alspaugh, S., Alstott, J., Nelson, A.A., Ariño de la Rubia, E., Arzi, A., Bahník, Š., Baik, J., Winther Balling, L., Banker, S., Baranger, D.A.A., Barr, D.J., Barros-Rivera, B., Bauer, M., Blaise, E., Boelen, L., Bohle Carbonell, K., Briers, R.A., Burkhard, O., Canela, M.A., Castrillo, L., Catlett, T., Chen, O., Clark, M., Cohn, B., Coppock, A., Cugueró-Escofet, N., Curran, P.G., Cyrus-Lai, W., Dai, D., Valentino Dalla Riva, G., Danielsson, H., Russo, R.d.F.S.M., de Silva, N., Derungs, C., Dondelinger, F., Duarte de Souza, C., Tyson Dube, B., Dubova, M., Dunn, B.M., Edelsbrunner, P.A., Finley, S., Fox, N., Gnambs, T., Gong, Y., Grand, E., Greenawalt, B., Han, D., Hanel, P.H.P., Hong, A.B., Hood, D., Hsueh, J., Huang, L., Hui, K.N., Hultman, K.A., Javaid, A., Ji Jiang, L., Jong, J., Kamdar, J., Kane, D., Kappler, G., Kaszubowski, E., Kavanagh, C.M., Khabsa, M., Kleinberg, B., Kouros, J., Krause, H., Krypotos, A.M., Lavbič, D., Ling Lee, R., Leffel, T., Yang Lim, W., Liverani, S., Loh, B., Lønsmann, D., Wei Low, J., Lu, A., MacDonald, K., Madan, C.R., Hjorth Madsen, L., Maimone, C., Mangold, A., Marshall, A., Matskewich, H.E., Mavon, K., McLain, K.L., McNamara, A.A., McNeill, M., Mertens, U., Miller, D., Moore, B., Moore, A., Nantz, E., Nasrullah, Z., Nejkovic, V., Nell, C.S., Nilsonne, G., Nolan, R., O'Brien, C.E., O'Neill, P., O'Shea, K., Olita, T., Otterbacher, J., Palsetia, D., Pereira, B., Pozdniakov, I., Protzko, J., Reyt, J.N., Riddle, T., (Akmal) Ridhwan Omar Ali, A., Ropovik, I., Rosenberg, J.M., Rothen, S., Schulte-Mecklenbeck, M., Sharma, N., Shotwell, G., Skarzynski, M., Stedden, W., Stodden, V., Stoffel, M.A., Stoltzman, S., Subbaiah, S., Tatman, R., Thibodeau, P.H., Tomkins, S., Valdivia, A., Druijff-van de Woestijne, G.B., Viana, L., Villesèche, F., Wadsworth, W.D., Wanders, F., Watts, K., Wells, J.D., Whelpley, C.E., Won, A., Wu, L., Yip, A., Youngflesh, C., Yu, J.C., Zandian, A., Zhang, L., Zibman, C., Uhlmann, E.L., Social Networks, Solidarity and Inequality, Leerstoel Buskens, Structural geology and EM, Experimental psychopathology, Leerstoel Engelhard, Department of Methodology and Statistics, Tilburg Experience Sampling Center (TESC), University of Zurich, Schweinsberg, Martin, Psychometrics and Statistics, Social Networks, Solidarity and Inequality, Leerstoel Buskens, Structural geology and EM, Experimental psychopathology, and Leerstoel Engelhard

Subjects
Organizational Behavior and Human Resource Management, TRANSPARENCY, 10009 Department of Informatics, Sample (statistics), 000 Computer science, knowledge & systems, 1407 Organizational Behavior and Human Resource Management, Scientific robustness, 3202 Applied Psychology, Scientific transparency, REPRODUCIBILITY, 650 Management & public relations, medicine, Econometrics, MANAGEMENT, QUALITY, business, Robustness (economics), Research question, Verbosity, CRISIS, Applied Psychology, Analysis-contingent results, Operationalization, Psykologi (exklusive tillämpad psykologi), 11476 Digital Society Initiative, AVAILABILITY, Researcher degrees of freedom, SCIENCE, cs_r, SOCIAL-PSYCHOLOGY, Crowdsourcing data analysis, Research reliability, Psychology (excluding Applied Psychology), Open data, Ranking, Transparency (graphic), REPLICABILITY, REPLICATION, medicine.symptom, Psychology
Abstract

The project was funded by a research grant from INSEAD and was also supported by the Swiss National Science Foundation under grant number 143411., In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists’ gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for organizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed., INSEAD, Swiss National Science Foundation (SNSF) European Commission 143411

Published
2021
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33. Same data, different conclusions: Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis

Author

Social Networks, Solidarity and Inequality, Leerstoel Buskens, Structural geology and EM, Experimental psychopathology, Leerstoel Engelhard, Schweinsberg, M., Feldman, M., Staub, N., van den Akker, O.R., van Aert, R.C.M., van Assen, M.A.L.M., Liu, Y., Althoff, T., Heer, J., Kale, A., Mohamed, Z., Amireh, H., Venkatesh Prasad, V., Bernstein, A., Robinson, E., Snellman, K., Sommer, S.A., Otner, S.M.G., Robinson, D.A., Madan, N., Silberzahn, R., Goldstein, P., Tierney, W., Murase, T., Mandl, B., Viganola, D., Strobl, C., Schaumans, C.B.C., Kelchtermans, S., Naseeb, C., Mason Garrison, S., Yarkoni, T., Richard Chan, C. S., Adie, P., Alaburda, P., Albers, C., Alspaugh, S., Alstott, J., Nelson, A.A., Ariño de la Rubia, E., Arzi, A., Bahník, Š., Baik, J., Winther Balling, L., Banker, S., Baranger, D.A.A., Barr, D.J., Barros-Rivera, B., Bauer, M., Blaise, E., Boelen, L., Bohle Carbonell, K., Briers, R.A., Burkhard, O., Canela, M.A., Castrillo, L., Catlett, T., Chen, O., Clark, M., Cohn, B., Coppock, A., Cugueró-Escofet, N., Curran, P.G., Cyrus-Lai, W., Dai, D., Valentino Dalla Riva, G., Danielsson, H., Russo, R.d.F.S.M., de Silva, N., Derungs, C., Dondelinger, F., Duarte de Souza, C., Tyson Dube, B., Dubova, M., Dunn, B.M., Edelsbrunner, P.A., Finley, S., Fox, N., Gnambs, T., Gong, Y., Grand, E., Greenawalt, B., Han, D., Hanel, P.H.P., Hong, A.B., Hood, D., Hsueh, J., Huang, L., Hui, K.N., Hultman, K.A., Javaid, A., Ji Jiang, L., Jong, J., Kamdar, J., Kane, D., Kappler, G., Kaszubowski, E., Kavanagh, C.M., Khabsa, M., Kleinberg, B., Kouros, J., Krause, H., Krypotos, A.M., Lavbič, D., Ling Lee, R., Leffel, T., Yang Lim, W., Liverani, S., Loh, B., Lønsmann, D., Wei Low, J., Lu, A., MacDonald, K., Madan, C.R., Hjorth Madsen, L., Maimone, C., Mangold, A., Marshall, A., Matskewich, H.E., Mavon, K., McLain, K.L., McNamara, A.A., McNeill, M., Mertens, U., Miller, D., Moore, B., Moore, A., Nantz, E., Nasrullah, Z., Nejkovic, V., Nell, C.S., Nilsonne, G., Nolan, R., O'Brien, C.E., O'Neill, P., O'Shea, K., Olita, T., Otterbacher, J., Palsetia, D., Pereira, B., Pozdniakov, I., Protzko, J., Reyt, J.N., Riddle, T., (Akmal) Ridhwan Omar Ali, A., Ropovik, I., Rosenberg, J.M., Rothen, S., Schulte-Mecklenbeck, M., Sharma, N., Shotwell, G., Skarzynski, M., Stedden, W., Stodden, V., Stoffel, M.A., Stoltzman, S., Subbaiah, S., Tatman, R., Thibodeau, P.H., Tomkins, S., Valdivia, A., Druijff-van de Woestijne, G.B., Viana, L., Villesèche, F., Wadsworth, W.D., Wanders, F., Watts, K., Wells, J.D., Whelpley, C.E., Won, A., Wu, L., Yip, A., Youngflesh, C., Yu, J.C., Zandian, A., Zhang, L., Zibman, C., Uhlmann, E.L., Social Networks, Solidarity and Inequality, Leerstoel Buskens, Structural geology and EM, Experimental psychopathology, Leerstoel Engelhard, Schweinsberg, M., Feldman, M., Staub, N., van den Akker, O.R., van Aert, R.C.M., van Assen, M.A.L.M., Liu, Y., Althoff, T., Heer, J., Kale, A., Mohamed, Z., Amireh, H., Venkatesh Prasad, V., Bernstein, A., Robinson, E., Snellman, K., Sommer, S.A., Otner, S.M.G., Robinson, D.A., Madan, N., Silberzahn, R., Goldstein, P., Tierney, W., Murase, T., Mandl, B., Viganola, D., Strobl, C., Schaumans, C.B.C., Kelchtermans, S., Naseeb, C., Mason Garrison, S., Yarkoni, T., Richard Chan, C. S., Adie, P., Alaburda, P., Albers, C., Alspaugh, S., Alstott, J., Nelson, A.A., Ariño de la Rubia, E., Arzi, A., Bahník, Š., Baik, J., Winther Balling, L., Banker, S., Baranger, D.A.A., Barr, D.J., Barros-Rivera, B., Bauer, M., Blaise, E., Boelen, L., Bohle Carbonell, K., Briers, R.A., Burkhard, O., Canela, M.A., Castrillo, L., Catlett, T., Chen, O., Clark, M., Cohn, B., Coppock, A., Cugueró-Escofet, N., Curran, P.G., Cyrus-Lai, W., Dai, D., Valentino Dalla Riva, G., Danielsson, H., Russo, R.d.F.S.M., de Silva, N., Derungs, C., Dondelinger, F., Duarte de Souza, C., Tyson Dube, B., Dubova, M., Dunn, B.M., Edelsbrunner, P.A., Finley, S., Fox, N., Gnambs, T., Gong, Y., Grand, E., Greenawalt, B., Han, D., Hanel, P.H.P., Hong, A.B., Hood, D., Hsueh, J., Huang, L., Hui, K.N., Hultman, K.A., Javaid, A., Ji Jiang, L., Jong, J., Kamdar, J., Kane, D., Kappler, G., Kaszubowski, E., Kavanagh, C.M., Khabsa, M., Kleinberg, B., Kouros, J., Krause, H., Krypotos, A.M., Lavbič, D., Ling Lee, R., Leffel, T., Yang Lim, W., Liverani, S., Loh, B., Lønsmann, D., Wei Low, J., Lu, A., MacDonald, K., Madan, C.R., Hjorth Madsen, L., Maimone, C., Mangold, A., Marshall, A., Matskewich, H.E., Mavon, K., McLain, K.L., McNamara, A.A., McNeill, M., Mertens, U., Miller, D., Moore, B., Moore, A., Nantz, E., Nasrullah, Z., Nejkovic, V., Nell, C.S., Nilsonne, G., Nolan, R., O'Brien, C.E., O'Neill, P., O'Shea, K., Olita, T., Otterbacher, J., Palsetia, D., Pereira, B., Pozdniakov, I., Protzko, J., Reyt, J.N., Riddle, T., (Akmal) Ridhwan Omar Ali, A., Ropovik, I., Rosenberg, J.M., Rothen, S., Schulte-Mecklenbeck, M., Sharma, N., Shotwell, G., Skarzynski, M., Stedden, W., Stodden, V., Stoffel, M.A., Stoltzman, S., Subbaiah, S., Tatman, R., Thibodeau, P.H., Tomkins, S., Valdivia, A., Druijff-van de Woestijne, G.B., Viana, L., Villesèche, F., Wadsworth, W.D., Wanders, F., Watts, K., Wells, J.D., Whelpley, C.E., Won, A., Wu, L., Yip, A., Youngflesh, C., Yu, J.C., Zandian, A., Zhang, L., Zibman, C., and Uhlmann, E.L.

Published
2021

34. Practices that Prevent the Formation of Cyanobacterial Blooms in Water Resources and Remove Cyanotoxins During Physical Treatment of Drinking Water

Author

Antoniou, M.G., primary, de La Cruz, A.A., additional, Pelaez, M.A., additional, Han, C., additional, He, X., additional, Dionysiou, D.D., additional, Song, W., additional, O'Shea, K., additional, Ho, L., additional, Newcombe, G., additional, Dixon, M.B., additional, Teixeira, M.R., additional, Triantis, T.M., additional, Hiskia, A., additional, Kaloudis, T., additional, Balasubramanian, R., additional, Pavagadhi, S., additional, and Sharma, V.K., additional

Published
2014
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36. Noggin and chordin have distinct activities in promoting lineage commitment of mouse embryonic stem (ES) Cells

Author

Gratsch, Theresa E. and O'Shea, K. Sue

Subjects
Embryology -- Research, Stem cells -- Research, Cell differentiation -- Physiological aspects, Neurons -- Physiological aspects, Biological sciences
Abstract

To examine the role of secreted signaling molecules and neurogenic genes in early development, we have developed a culture system for the controlled differentiation of mouse embryonic stem (ES) cells. In the current investigation, two of the earliest identified BMP antagonists/neural-inducing factors, noggin and chordin, were expressed in pluripotent mouse ES cells. Neurons were present as early as 24 h following transfection of ES cells with a pCS2/noggin expression plasmid, with differentiation peaking at 72 h. With neuronal differentiation, stem cell marker genes were down-regulated and neural determination genes expressed. Coculture experiments and exposure to noggin-conditioned medium produced similar neuronal differentiation of control ES cells, while addition of BMP-4 to noggin expressants strikingly inhibited neuronal differentiation. Transfection of ES cells with a pCS2/chordin expression vector or exposure to chordin-conditioned medium produced a more complex pattern of differentiation; ES cells formed neurons, mesenchymal cells as well as N-CAM-positive, nestin-positive neuroepithelial progenitors. These data suggest that, consistent with their different expression fields, noggin and chordin may play distinct roles in patterning the early mouse embryo. Key Words: BMP; differentiation; induction; neuron; nervous system; node; transfection.

Published
2002

44. Sacrococcygeal teratomas: midline reconstruction improves cosmesis without compromising outcomes.

Author

O'Shea, K. M., Sanders, E., Farrelly, P. J., Wilkinson, D. J., Minshull, K., and Craigie, R. J.

Subjects
SCARS, PSYCHOLOGICAL adjustment testing, PATIENT satisfaction, DISEASES, TERATOMA, BACK, PELVIC tumors
Abstract

Aim: Several studies have addressed the long-term functional, psychosexual and psychosocial outcomes following sacrococcygeal teratoma (SCT) excision. It is well reported that the classical chevron incision and reconstruction can leave a cosmetically unsatisfactory result; however, there is little in the literature focussed on improving this outcome. In our institution the preference is to perform a midline reconstruction, where possible, this is felt to improve appearance without compromising the oncological or functional outcome. The aim of this study was to evaluate patient-perceived cosmetic outcomes of the midline reconstruction.Methods: All patients undergoing surgery for SCT between 2007 and 2020 were included in the study. Patient demographics, operation type, functional outcome and recurrence were all recorded. The primary outcome measure was patient/parent satisfaction with the cosmetic appearance. This was assessed using both qualitative and quantitative methodologies. Following ethical approval parents were asked questions from two existing validated patient outcome questionnaires: "Patient and Observer Scar Assessment Scale" (POSAS) v2.0 and the "Patient Scar Assessment Questionnaire".Results: Thirty-two patients underwent surgery at our institution for SCT during the study period. Twenty-four had a posterior approach with midline reconstruction, two laparotomy and excision (excluded from this study) and six had a combined approach. Median follow-up was 35 months (8.5-96 months). There were no recurrences. 4/30 (13%) have persistent urological symptoms, and 1/30 (3%) has constipation requiring bowel management. Questionnaires were sent to 26/30 families with a 77% return rate. Median total score was 11 (7.4-17.5) on a 60-point scale (6, as normal skin, 60, worst imaginable scar). Twenty (95%) reported that the scar never affects the child's activities and 15 (71%) said they are "not at all" conscious of the scar.Conclusion: Scars can lead to an array of cosmetic, functional, and psychological consequences and as such consideration needs to be given to scarring following surgery for sacrococcygeal teratomas. This study demonstrates that a midline reconstruction produces a cosmetically favourable outcome. We, therefore, recommend where appropriate a midline reconstruction should be considered for SCT. [ABSTRACT FROM AUTHOR]

Published
2022
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