37 results on '"Ortega DG"'
Search Results
2. Upconversion nanoparticle-assisted single-molecule assay for detecting circulating antigens of aggressive prostate cancer.
- Author
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Chen, Y, Shimoni, O, Huang, G, Wen, S, Liao, J, Duong, HTT, Maddahfar, M, Su, QP, Ortega, DG, Lu, Y, Campbell, DH, Walsh, BJ, Jin, D, Chen, Y, Shimoni, O, Huang, G, Wen, S, Liao, J, Duong, HTT, Maddahfar, M, Su, QP, Ortega, DG, Lu, Y, Campbell, DH, Walsh, BJ, and Jin, D
- Abstract
Sensitive and quantitative detection of molecular biomarkers is crucial for the early diagnosis of diseases like metabolic syndrome and cancer. Here we present a single-molecule sandwich immunoassay by imaging the number of single nanoparticles to diagnose aggressive prostate cancer. Our assay employed the photo-stable upconversion nanoparticles (UCNPs) as labels to detect the four types of circulating antigens in blood circulation, including glypican-1 (GPC-1), leptin, osteopontin (OPN), and vascular endothelial growth factor (VEGF), as their serum concentrations indicate aggressive prostate cancer. Under a wide-field microscope, a single UCNP doped with thousands of lanthanide ions can emit sufficiently bright anti-Stokes' luminescence to become quantitatively detectable. By counting every single streptavidin-functionalized UCNP which specifically labeled on each sandwich immune complex across multiple fields of views, we achieved the Limit of Detection (LOD) of 0.0123 ng/ml, 0.2711 ng/ml, 0.1238 ng/ml, and 0.0158 ng/ml for GPC-1, leptin, OPN and VEGF, respectively. The serum circulating level of GPC-1, leptin, OPN, and VEGF in a mixture of 10 healthy normal human serum was 25.17 ng/ml, 18.04 ng/ml, 11.34 ng/ml, and 1.55 ng/ml, which was within the assay dynamic detection range for each analyte. Moreover, a 20% increase of GPC-1 and OPN was observed by spiking the normal human serum with recombinant antigens to confirm the accuracy of the assay. We observed no cross-reactivity among the four biomarker analytes, which eliminates the false positives and enhances the detection accuracy. The developed single upconversion nanoparticle-assisted single-molecule assay suggests its potential in clinical usage for prostate cancer detection by monitoring tiny concentration differences in a panel of serum biomarkers.
- Published
- 2022
3. Disentangling single-cell omics representation with a power spectral density-based feature extraction.
- Author
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Zandavi, SM, Koch, FC, Vijayan, A, Zanini, F, Mora, FV, Ortega, DG, Vafaee, F, Zandavi, SM, Koch, FC, Vijayan, A, Zanini, F, Mora, FV, Ortega, DG, and Vafaee, F
- Abstract
Emerging single-cell technologies provide high-resolution measurements of distinct cellular modalities opening new avenues for generating detailed cellular atlases of many and diverse tissues. The high dimensionality, sparsity, and inaccuracy of single cell sequencing measurements, however, can obscure discriminatory information, mask cellular subtype variations and complicate downstream analyses which can limit our understanding of cell function and tissue heterogeneity. Here, we present a novel pre-processing method (scPSD) inspired by power spectral density analysis that enhances the accuracy for cell subtype separation from large-scale single-cell omics data. We comprehensively benchmarked our method on a wide range of single-cell RNA-sequencing datasets and showed that scPSD pre-processing, while being fast and scalable, significantly reduces data complexity, enhances cell-type separation, and enables rare cell identification. Additionally, we applied scPSD to transcriptomics and chromatin accessibility cell atlases and demonstrated its capacity to discriminate over 100 cell types across the whole organism and across different modalities of single-cell omics data.
- Published
- 2022
4. Upconversion nanoparticle-assisted single-molecule assay for detecting circulating antigens of aggressive prostate cancer
- Author
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Chen, Y, Shimoni, O, Huang, G, Wen, S, Liao, J, Duong, HTT, Maddahfar, M, Su, QP, Ortega, DG, Lu, Y, Campbell, DH, Walsh, BJ, and Jin, D
- Subjects
Leptin ,Male ,Vascular Endothelial Growth Factor A ,Immunology ,Humans ,Nanoparticles ,Prostatic Neoplasms ,0601 Biochemistry and Cell Biology ,Biomarkers - Abstract
Sensitive and quantitative detection of molecular biomarkers is crucial for the early diagnosis of diseases like metabolic syndrome and cancer. Here we present a single-molecule sandwich immunoassay by imaging the number of single nanoparticles to diagnose aggressive prostate cancer. Our assay employed the photo-stable upconversion nanoparticles (UCNPs) as labels to detect the four types of circulating antigens in blood circulation, including glypican-1 (GPC-1), leptin, osteopontin (OPN), and vascular endothelial growth factor (VEGF), as their serum concentrations indicate aggressive prostate cancer. Under a wide-field microscope, a single UCNP doped with thousands of lanthanide ions can emit sufficiently bright anti-Stokes' luminescence to become quantitatively detectable. By counting every single streptavidin-functionalized UCNP which specifically labeled on each sandwich immune complex across multiple fields of views, we achieved the Limit of Detection (LOD) of 0.0123 ng/ml, 0.2711 ng/ml, 0.1238 ng/ml, and 0.0158 ng/ml for GPC-1, leptin, OPN and VEGF, respectively. The serum circulating level of GPC-1, leptin, OPN, and VEGF in a mixture of 10 healthy normal human serum was 25.17 ng/ml, 18.04 ng/ml, 11.34 ng/ml, and 1.55 ng/ml, which was within the assay dynamic detection range for each analyte. Moreover, a 20% increase of GPC-1 and OPN was observed by spiking the normal human serum with recombinant antigens to confirm the accuracy of the assay. We observed no cross-reactivity among the four biomarker analytes, which eliminates the false positives and enhances the detection accuracy. The developed single upconversion nanoparticle-assisted single-molecule assay suggests its potential in clinical usage for prostate cancer detection by monitoring tiny concentration differences in a panel of serum biomarkers.
- Published
- 2021
5. Mendelian randomisation study of smoking exposure in relation to breast cancer risk
- Author
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Park, HA, Neumeyer, S, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Augustinsson, A, Baten, A, Beane Freeman, LE, Becher, H, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bogdanova, NV, Bojesen, SE, Brauch, H, Brenner, H, Brucker, SY, Burwinkel, B, Campa, D, Canzian, F, Castelao, JE, Chanock, SJ, Chenevix-Trench, G, Clarke, CL, Børresen-Dale, A-L, Grenaker Alnæs, GI, Sahlberg, KK, Ottestad, L, Kåresen, R, Schlichting, E, Holmen, MM, Sauer, T, Haakensen, V, Engebråten, O, Naume, B, Fosså, A, Kiserud, CE, Reinertsen, KV, Helland, Å, Riis, M, Geisler, J, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Dörk, T, dos-Santos-Silva, I, Dwek, M, Eccles, DM, Eliassen, AH, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Flyger, H, Fritschi, L, García-Closas, M, García-Sáenz, JA, Gaudet, MM, Giles, GG, Glendon, G, Goldberg, MS, Goldgar, DE, González-Neira, A, Grip, M, Guénel, P, Hahnen, E, Haiman, CA, Håkansson, N, Hall, P, Hamann, U, Han, S, Harkness, EF, Hart, SN, He, W, Heemskerk-Gerritsen, BAM, Hopper, JL, Hunter, DJ, Clarke, C, Marsh, D, Scott, R, Baxter, R, Yip, D, Carpenter, J, Davis, A, Pathmanathan, N, Simpson, P, Graham, D, Sachchithananthan, M, Amor, D, Andrews, L, Antill, Y, Balleine, R, Beesley, J, Bennett, I, Bogwitz, M, Botes, L, Brennan, M, Brown, M, Buckley, M, Burke, J, Butow, P, Caldon, L, Campbell, I, Chauhan, D, Chauhan, M, Christian, A, Cohen, P, Colley, A, Crook, A, Cui, J, Cummings, M, Dawson, S-J, DeFazio, A, Delatycki, M, Dickson, R, Dixon, J, Edkins, T, Edwards, S, Farshid, G, Fellows, A, Fenton, G, Field, M, Flanagan, J, Fong, P, Forrest, L, Fox, S, French, J, Friedlander, M, Gaff, C, Gattas, M, George, P, Greening, S, Harris, M, Hart, S, Hayward, N, Hopper, J, Hoskins, C, Hunt, C, James, P, Jenkins, M, Kidd, A, Kirk, J, Koehler, J, Kollias, J, Lakhani, S, Lawrence, M, Lindeman, G, Lipton, L, Lobb, L, Mann, G, McLachlan, SA, Meiser, B, Milne, R, Nightingale, S, O’Connell, S, O’Sullivan, S, Ortega, DG, Pachter, N, Patterson, B, Pearn, A, Phillips, K, Pieper, E, Rickard, E, Robinson, B, Saleh, M, Salisbury, E, Saunders, C, Saunus, J, Scott, C, Sexton, A, Shelling, A, Southey, M, Spurdle, A, Taylor, J, Taylor, R, Thorne, H, Trainer, A, Tucker, K, Visvader, J, Walker, L, Williams, R, Winship, I, Young, MA, Jager, A, Jakubowska, A, John, EM, Jung, A, Kaaks, R, Kapoor, PM, Keeman, R, Khusnutdinova, E, Kitahara, CM, Koppert, LB, Koutros, S, Kristensen, VN, Kurian, AW, Lacey, J, Lambrechts, D, Le Marchand, L, Lo, W-Y, Lubiński, J, Mannermaa, A, Manoochehri, M, Margolin, S, Martinez, ME, Mavroudis, D, Meindl, A, Menon, U, Milne, RL, Muranen, TA, Nevanlinna, H, Newman, WG, Nordestgaard, BG, Offit, K, Olshan, AF, Olsson, H, Park-Simon, T-W, Peterlongo, P, Peto, J, Plaseska-Karanfilska, D, Presneau, N, Radice, P, Rennert, G, Rennert, HS, Romero, A, Saloustros, E, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Schoemaker, MJ, Schwentner, L, Shah, M, Shu, X-O, Simard, J, Smeets, A, Southey, MC, Spinelli, JJ, Stevens, V, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Tomlinson, I, Troester, MA, Truong, T, Vachon, CM, van Veen, EM, Vijai, J, Wang, S, Wendt, C, Winqvist, R, Wolk, A, Ziogas, A, Dunning, AM, Pharoah, PDP, Easton, DF, Zheng, W, Kraft, P, Chang-Claude, J, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Park, Hanla A. [0000-0001-8055-3729], Dennis, Joe [0000-0003-4591-1214], Augustinsson, Annelie [0000-0003-3415-0536], Brenner, Hermann [0000-0002-6129-1572], Canzian, Federico [0000-0002-4261-4583], Cox, Angela [0000-0002-5138-1099], Devilee, Peter [0000-0002-8023-2009], Fasching, Peter A. [0000-0003-4885-8471], Harkness, Elaine F. [0000-0001-6625-7739], Hart, Steven N. [0000-0001-7714-2734], Heemskerk-Gerritsen, Bernadette A. M. [0000-0002-9724-6693], Jakubowska, Anna [0000-0002-5650-0501], Kapoor, Pooja Middha [0000-0001-5503-8215], Kurian, Allison W. [0000-0002-6175-9470], Newman, William G. [0000-0002-6382-4678], Peterlongo, Paolo [0000-0001-6951-6855], Peto, Julian [0000-0002-1685-8912], Sawyer, Elinor J. [0000-0001-8285-4111], Scott, Christopher [0000-0003-1340-0647], Smeets, Ann [0000-0002-5091-6602], Tomlinson, Ian [0000-0003-3037-1470], Truong, Thérèse [0000-0002-2943-6786], Pharoah, Paul D. P. [0000-0001-8494-732X], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Oncology ,Medicin och hälsovetenskap ,Cancer Research ,Genotyping Techniques ,Breast Neoplasms ,Case-Control Studies ,Cigarette Smoking ,Female ,Genetic Pleiotropy ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Mendelian Randomization Analysis ,Polymorphism, Single Nucleotide ,ALCOHOL ,Medical and Health Sciences ,0302 clinical medicine ,Breast cancer ,Pleiotropy ,Epidemiology ,Medicine ,TOBACCO ,Breast Neoplasms/epidemiology ,Cigarette Smoking/adverse effects ,WOMEN ,ASSOCIATION ,Single Nucleotide ,3. Good health ,Substance abuse ,692/699/67/1347 ,030220 oncology & carcinogenesis ,Life Sciences & Biomedicine ,692/499 ,medicine.medical_specialty ,3122 Cancers ,Single-nucleotide polymorphism ,Article ,03 medical and health sciences ,Internal medicine ,ddc:610 ,Polymorphism ,Genetic association ,Science & Technology ,business.industry ,Cancer ,medicine.disease ,030104 developmental biology ,Clinical research ,Risk factors ,TISSUE ,INFERENCE ,CIGARETTE-SMOKING ,business - Abstract
Background Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. Methods We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. Results Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07–1.30, P = 0.11 × 10–2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78–1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. Conclusion Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.
- Published
- 2021
- Full Text
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6. Disentangling single-cell omics representation with a power spectral density-based feature extraction
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Zandavi, SM, Koch, F, Vijayan, A, Zanini, F, Mora, FV, Ortega, DG, Vafaee, F, Zandavi, SM, Koch, F, Vijayan, A, Zanini, F, Mora, FV, Ortega, DG, and Vafaee, F
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- 2021
7. Publisher Correction: Homologous recombination DNA repair defects in PALB2-associated breast cancers (npj Breast Cancer, (2019), 5, 1, (23), 10.1038/s41523-019-0115-9)
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Li, A, Geyer, FC, Blecua, P, Lee, JY, Selenica, P, Brown, DN, Pareja, F, Lee, SSK, Kumar, R, Rivera, B, Bi, R, Piscuoglio, S, Wen, HY, Lozada, JR, Gularte-Mérida, R, Cavallone, L, Aghmesheh, M, Amor, D, Andrews, L, Antill, Y, Balleine, R, Beesley, J, Blackburn, A, Bogwitz, M, Brown, M, Burgess, M, Burke, J, Butow, P, Caldon, L, Campbell, I, Christian, A, Clarke, C, Cohen, P, Crook, A, Cui, J, Cummings, M, Dawson, SJ, De Fazio, A, Delatycki, M, Dobrovic, A, Dudding, T, Duijf, P, Edkins, E, Edwards, S, Farshid, G, Fellows, A, Field, M, Flanagan, J, Fong, P, Forbes, J, Forrest, L, Fox, S, French, J, Friedlander, M, Ortega, DG, Gattas, M, Giles, G, Gill, G, Gleeson, M, Greening, S, Haan, E, Harris, M, Hayward, N, Hickie, I, Hopper, J, Hunt, C, James, P, Jenkins, M, Kefford, R, Kentwell, M, Kirk, J, Kollias, J, Lakhani, S, Lindeman, G, Lipton, L, Lobb, L, Lok, S, Macrea, F, Mann, G, Marsh, D, McLachlan, SA, Meiser, B, Milne, R, Nightingale, S, O’Connell, S, Pachter, N, Patterson, B, Phillips, K, Saleh, M, Salisbury, E, Saunders, C, Saunus, J, Scott, C, Scott, R, Sexton, A, Shelling, A, Simpson, P, Spigelman, A, Spurdle, M, and Stone, J
- Abstract
© 2019, The Author(s). In the original version of this paper, the link to the data record in the Data Availability Statement was incorrectly listed as https:// doi.org/10.6084/m9.figshare.8138912.44. The link has been corrected to https://doi.org/10.6084/m9.figshare.8138912. This has been corrected in the HTML and PDF versions of this article.
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- 2019
8. Development and validation of a targeted gene sequencing panel for application to disparate cancers
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McCabe, MJ, Gauthier, MEA, Chan, CL, Thompson, TJ, De Sousa, SMC, Puttick, C, Grady, JP, Gayevskiy, V, Tao, J, Ying, K, Cipponi, A, Deng, N, Swarbrick, A, Thomas, ML, Lord, RV, Johns, AL, Kohonen-Corish, M, O’Toole, SA, Clark, J, Mueller, SA, Gupta, R, McCormack, AI, Dinger, ME, Cowley, MJ, Aghmesheh, M, Amor, D, Andrews, L, Antill, Y, Armitage, S, Arnold, L, Balleine, R, Bastick, P, Beesley, J, Beilby, J, Bennett, I, Blackburn, A, Bogwitz, M, Botes, L, Brennan, M, Brown, M, Buckley, M, Burgess, M, Burke, J, Butow, P, Caldon, L, Callen, D, Campbell, I, Chauhan, D, Chauhan, M, Chenevix-Trench, G, Christian, A, Clarke, C, Cohen, P, Colley, A, Crook, A, Cui, J, Culling, B, Cummings, M, Dawson, SJ, deFazio, A, Delatycki, M, Dickson, R, Dixon, J, Dobrovic, A, Dudding, T, Edkins, T, Edwards, S, Eisenbruch, M, Farshid, G, Fellows, A, Fenton, G, Field, M, Flanagan, J, Fong, P, Forrest, L, Fox, S, French, J, Friedlander, M, Gaff, C, Ortega, DG, Gattas, M, George, P, Giles, G, Gill, G, Greening, S, Haan, E, Harris, M, Hart, S, Hayward, N, Heiniger, L, Hopper, J, Hunt, C, James, P, Jenkins, M, Kefford, R, Kidd, A, Kirk, J, Koehler, J, Kollias, J, and Lakhani, S
- Abstract
© 2019, The Author(s). Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy.
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- 2019
9. Homologous recombination DNA repair defects in PALB2-associated breast cancers
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Li, A, Geyer, FC, Blecua, P, Lee, JY, Selenica, P, Brown, DN, Pareja, F, Lee, SSK, Kumar, R, Rivera, B, Bi, R, Piscuoglio, S, Wen, HY, Lozada, JR, Gularte-Mérida, R, Cavallone, L, Aghmesheh, M, Amor, D, Andrews, L, Antill, Y, Balleine, R, Beesley, J, Blackburn, A, Bogwitz, M, Brown, M, Burgess, M, Burke, J, Butow, P, Caldon, L, Campbell, I, Christian, A, Clarke, C, Cohen, P, Crook, A, Cui, J, Cummings, M, Dawson, SJ, De Fazio, A, Delatycki, M, Dobrovic, A, Dudding, T, Duijf, P, Edkins, E, Edwards, S, Farshid, G, Fellows, A, Field, M, Flanagan, J, Fong, P, Forbes, J, Forrest, L, Fox, S, French, J, Friedlander, M, Ortega, DG, Gattas, M, Giles, G, Gill, G, Gleeson, M, Greening, S, Haan, E, Harris, M, Hayward, N, Hickie, I, Hopper, J, Hunt, C, James, P, Jenkins, M, Kefford, R, Kentwell, M, Kirk, J, Kollias, J, Lakhani, S, Lindeman, G, Lipton, L, Lobb, L, Lok, S, Macrea, F, Mann, G, Marsh, D, McLachlan, SA, Meiser, B, Milne, R, Nightingale, S, O’Connell, S, Pachter, N, Patterson, B, Phillips, K, Saleh, M, Salisbury, E, Saunders, C, Saunus, J, Scott, C, Scott, R, Sexton, A, Shelling, A, Simpson, P, Spigelman, A, Spurdle, M, and Stone, J
- Abstract
© 2019, The Author(s). Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD.
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- 2019
10. Homologous recombination DNA repair defects in PALB2-associated breast cancers (vol 5, 23, 2019)
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Li, A, Geyer, FC, Blecua, P, Lee, JY, Selenica, P, Brown, DN, Pareja, F, Lee, SSK, Kumar, R, Rivera, B, Bi, R, Piscuoglio, S, Wen, HY, Lozada, JR, Gularte-Merida, R, Cavallone, L, Rezoug, Z, Tu, N-D, Peterlongo, P, Tondini, C, Terkelsen, T, Ronlund, K, Boonen, SE, Mannerma, A, Winqvist, R, Janatova, M, Rajadurai, P, Xia, B, Norton, L, Robson, ME, Ng, P-S, Looi, L-M, Southey, MC, Weigelt, B, Soo-Hwang, T, Tischkowitz, M, Foulkes, WD, Reis-Filho, JS, Aghmesheh, M, Amor, D, Andrews, L, Antill, Y, Balleine, R, Beesley, J, Blackburn, A, Bogwitz, M, Brown, M, Burgess, M, Burke, J, Butow, P, Caldon, L, Campbell, I, Christian, A, Clarke, C, Cohen, P, Crook, A, Cui, J, Cummings, M, Dawson, S-J, De Fazio, A, Delatycki, M, Dobrovic, A, Dudding, T, Duijf, P, Edkins, E, Edwards, S, Farshid, G, Fellows, A, Field, M, Flanagan, J, Fong, P, Forbes, J, Forrest, L, Fox, S, French, J, Friedlander, M, Ortega, DG, Gattas, M, Giles, G, Gill, G, Gleeson, M, Greening, S, Haan, E, Harris, M, Hayward, N, Hickie, I, Hopper, J, Hunt, C, James, P, Jenkins, M, Kefford, R, Kentwell, M, Kirk, J, Kollias, J, Lakhani, S, Lindeman, G, Lipton, L, Lobb, L, Lok, S, Macrea, F, Mann, G, Marsh, D, McLachlan, S-A, Meiser, B, Milne, R, Nightingale, S, O'Connell, S, Pachter, N, Patterson, B, Phillips, K, Saleh, M, Salisbury, E, Saunders, C, Saunus, J, Scott, C, Scott, R, Sexton, A, Shelling, A, Simpson, P, Spigelman, A, Spurdle, M, Stone, J, Taylor, J, Thorne, H, Trainer, A, Trench, G, Tucker, K, Visvader, J, Walker, L, Wallis, M, Williams, R, Winship, I, Wu, K, Young, MA, Li, A, Geyer, FC, Blecua, P, Lee, JY, Selenica, P, Brown, DN, Pareja, F, Lee, SSK, Kumar, R, Rivera, B, Bi, R, Piscuoglio, S, Wen, HY, Lozada, JR, Gularte-Merida, R, Cavallone, L, Rezoug, Z, Tu, N-D, Peterlongo, P, Tondini, C, Terkelsen, T, Ronlund, K, Boonen, SE, Mannerma, A, Winqvist, R, Janatova, M, Rajadurai, P, Xia, B, Norton, L, Robson, ME, Ng, P-S, Looi, L-M, Southey, MC, Weigelt, B, Soo-Hwang, T, Tischkowitz, M, Foulkes, WD, Reis-Filho, JS, Aghmesheh, M, Amor, D, Andrews, L, Antill, Y, Balleine, R, Beesley, J, Blackburn, A, Bogwitz, M, Brown, M, Burgess, M, Burke, J, Butow, P, Caldon, L, Campbell, I, Christian, A, Clarke, C, Cohen, P, Crook, A, Cui, J, Cummings, M, Dawson, S-J, De Fazio, A, Delatycki, M, Dobrovic, A, Dudding, T, Duijf, P, Edkins, E, Edwards, S, Farshid, G, Fellows, A, Field, M, Flanagan, J, Fong, P, Forbes, J, Forrest, L, Fox, S, French, J, Friedlander, M, Ortega, DG, Gattas, M, Giles, G, Gill, G, Gleeson, M, Greening, S, Haan, E, Harris, M, Hayward, N, Hickie, I, Hopper, J, Hunt, C, James, P, Jenkins, M, Kefford, R, Kentwell, M, Kirk, J, Kollias, J, Lakhani, S, Lindeman, G, Lipton, L, Lobb, L, Lok, S, Macrea, F, Mann, G, Marsh, D, McLachlan, S-A, Meiser, B, Milne, R, Nightingale, S, O'Connell, S, Pachter, N, Patterson, B, Phillips, K, Saleh, M, Salisbury, E, Saunders, C, Saunus, J, Scott, C, Scott, R, Sexton, A, Shelling, A, Simpson, P, Spigelman, A, Spurdle, M, Stone, J, Taylor, J, Thorne, H, Trainer, A, Trench, G, Tucker, K, Visvader, J, Walker, L, Wallis, M, Williams, R, Winship, I, Wu, K, and Young, MA
- Abstract
[This corrects the article DOI: 10.1038/s41523-019-0115-9.].
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- 2019
11. Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes
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Mavaddat, N, Michailidou, K, Dennis, J, Lush, M, Fachal, L, Lee, A, Tyrer, JP, Chen, T-H, Wang, Q, Bolla, MK, Yang, X, Adank, MA, Ahearn, T, Aittomaki, K, Allen, J, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Auer, PL, Auvinen, P, Barrdahl, M, Freeman, LEB, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bernstein, L, Blomqvist, C, Bogdanova, N, Bojesen, SE, Bonanni, B, Borresen-Dale, A-L, Brauch, H, Bremer, M, Brenner, H, Brentnall, A, Brock, IW, Brooks-Wilson, A, Brucker, SY, Bruening, T, Burwinkel, B, Campa, D, Carter, BD, Castelao, JE, Chanock, SJ, Chlebowski, R, Christiansen, H, Clarke, CL, Collee, JM, Cordina-Duverger, E, Cornelissen, S, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Doerk, T, dos-Santos-Silva, I, Dumont, M, Durcan, L, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Ellberg, C, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Fletcher, O, Flyger, H, Foersti, A, Fritschi, L, Gabrielson, M, Gago-Dominguez, M, Gapstur, SM, Garcia-Saenz, JA, Gaudet, MM, Georgoulias, V, Giles, GG, Gilyazova, IR, Glendon, G, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Alnaes, GIG, Grip, M, Gronwald, J, Grundy, A, Guenel, P, Haeberle, L, Hahnen, E, Haiman, CA, Hakansson, N, Hamann, U, Hankinson, SE, Harkness, EF, Hart, SN, He, W, Hein, A, Heyworth, J, Hillemanns, P, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Howell, A, Huang, G, Humphreys, K, Hunter, DJ, Jakimovska, M, Jakubowska, A, Janni, W, John, EM, Johnson, N, Jones, ME, Jukkola-Vuorinen, A, Jung, A, Kaaks, R, Kaczmarek, K, Kataja, V, Keeman, R, Kerin, MJ, Khusnutdinova, E, Kiiski, J, Knight, JA, Ko, Y-D, Kosma, V-M, Koutros, S, Kristensen, VN, Kruger, U, Kuehl, T, Lambrechts, D, Le Marchand, L, Lee, E, Lejbkowicz, F, Lilyquist, J, Lindblom, A, Lindstrom, S, Lissowska, J, Lo, W-Y, Loibl, S, Long, J, Lubinski, J, Lux, MP, MacInnis, RJ, Maishman, T, Makalic, E, Kostovska, IM, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Martinez, ME, Mavroudis, D, McLean, C, Meindl, A, Menon, U, Middha, P, Miller, N, Moreno, F, Mulligan, AM, Mulot, C, Munoz-Garzon, VM, Neuhausen, SL, Nevanlinna, H, Neven, P, Newman, WG, Nielsen, SF, Nordestgaard, BG, Norman, A, Offit, K, Olson, JE, Olsson, H, Orr, N, Pankratz, VS, Park-Simon, T-W, Perez, JIA, Perez-Barrios, C, Peterlongo, P, Peto, J, Pinchev, M, Plaseska-Karanfilska, D, Polley, EC, Prentice, R, Presneau, N, Prokofyeva, D, Purrington, K, Pylkas, K, Rack, B, Radice, P, Rau-Murthy, R, Rennert, G, Rennert, HS, Rhenius, V, Robson, M, Romero, A, Ruddy, KJ, Ruebner, M, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmidt, DF, Schmutzler, RK, Schneeweiss, A, Schoemaker, MJ, Schumacher, F, Schuermann, P, Schwentner, L, Scott, C, Scott, RJ, Seynaeve, C, Shah, M, Sherman, ME, Shrubsole, MJ, Shu, X-O, Slager, S, Smeets, A, Sohn, C, Soucy, P, Southey, MC, Spinelli, JJ, Stegmaier, C, Stone, J, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Thoene, K, Tollenaar, RAEM, Tomlinson, I, Truong, T, Tzardi, M, Ulmer, H-U, Untch, M, Vachon, CM, van Veen, EM, Vijai, J, Weinberg, CR, Wendt, C, Whittemore, AS, Wildiers, H, Willett, W, Winqvist, R, Wolk, A, Yang, XR, Yannoukakos, D, Zhang, Y, Zheng, W, Ziogas, A, Clarke, C, Balleine, R, Baxter, R, Braye, S, Carpenter, J, Dahlstrom, J, Forbes, J, Lee, CS, Marsh, D, Morey, A, Pathmanathan, N, Scott, R, Simpson, P, Spigelman, A, Wilcken, N, Yip, D, Zeps, N, Sexton, A, Dobrovic, A, Christian, A, Trainer, A, Fellows, A, Shelling, A, De Fazio, A, Blackburn, A, Crook, A, Meiser, B, Patterson, B, Saunders, C, Hunt, C, Amor, D, Ortega, DG, Edkins, E, Salisbury, E, Haan, E, Macrea, F, Farshid, G, Lindeman, G, Trench, G, Mann, G, Giles, G, Gill, G, Thorne, H, Campbell, I, Hickie, I, Caldon, L, Winship, I, Cui, J, Flanagan, J, Kollias, J, Visvader, J, Taylor, J, Burke, J, Saunus, J, Forbs, J, Hopper, J, Beesley, J, Kirk, J, French, J, Tucker, K, Wu, K, Phillips, K, Forrest, L, Lipton, L, Andrews, L, Lobb, L, Walker, L, Kentwell, M, Spurdle, M, Cummings, M, Gleeson, M, Harris, M, Jenkins, M, Young, MA, Delatycki, M, Wallis, M, Burgess, M, Brown, M, Southey, M, Bogwitz, M, Field, M, Friedlander, M, Gattas, M, Saleh, M, Aghmesheh, M, Hayward, N, Pachter, N, Cohen, P, Duijf, P, James, P, Fong, P, Butow, P, Williams, R, Kefford, R, Simard, J, Balleine, R-M, Dawson, S-J, Lok, S, O'connell, S, Greening, S, Nightingale, S, Edwards, S, Fox, S, McLachlan, S-A, Lakhani, S, Dudding, T, Antill, Y, Sahlberg, KK, Ottestad, L, Karesen, R, Schlichting, E, Holmen, MM, Sauer, T, Haakensen, V, Engebraten, O, Naume, B, Fossa, A, Kiserud, CE, Reinertsen, K, Helland, A, Riis, M, Geisler, J, Dunning, AM, Thompson, DJ, Chenevix-Trench, G, Chang-Claude, J, Schmidt, MK, Hall, P, Milne, RL, Pharoah, PDP, Antoniou, AC, Chatterjee, N, Kraft, P, Garcia-Closas, M, Easton, DF, Mavaddat, N, Michailidou, K, Dennis, J, Lush, M, Fachal, L, Lee, A, Tyrer, JP, Chen, T-H, Wang, Q, Bolla, MK, Yang, X, Adank, MA, Ahearn, T, Aittomaki, K, Allen, J, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Auer, PL, Auvinen, P, Barrdahl, M, Freeman, LEB, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bernstein, L, Blomqvist, C, Bogdanova, N, Bojesen, SE, Bonanni, B, Borresen-Dale, A-L, Brauch, H, Bremer, M, Brenner, H, Brentnall, A, Brock, IW, Brooks-Wilson, A, Brucker, SY, Bruening, T, Burwinkel, B, Campa, D, Carter, BD, Castelao, JE, Chanock, SJ, Chlebowski, R, Christiansen, H, Clarke, CL, Collee, JM, Cordina-Duverger, E, Cornelissen, S, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Doerk, T, dos-Santos-Silva, I, Dumont, M, Durcan, L, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Ellberg, C, Engel, C, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Fletcher, O, Flyger, H, Foersti, A, Fritschi, L, Gabrielson, M, Gago-Dominguez, M, Gapstur, SM, Garcia-Saenz, JA, Gaudet, MM, Georgoulias, V, Giles, GG, Gilyazova, IR, Glendon, G, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Alnaes, GIG, Grip, M, Gronwald, J, Grundy, A, Guenel, P, Haeberle, L, Hahnen, E, Haiman, CA, Hakansson, N, Hamann, U, Hankinson, SE, Harkness, EF, Hart, SN, He, W, Hein, A, Heyworth, J, Hillemanns, P, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Howell, A, Huang, G, Humphreys, K, Hunter, DJ, Jakimovska, M, Jakubowska, A, Janni, W, John, EM, Johnson, N, Jones, ME, Jukkola-Vuorinen, A, Jung, A, Kaaks, R, Kaczmarek, K, Kataja, V, Keeman, R, Kerin, MJ, Khusnutdinova, E, Kiiski, J, Knight, JA, Ko, Y-D, Kosma, V-M, Koutros, S, Kristensen, VN, Kruger, U, Kuehl, T, Lambrechts, D, Le Marchand, L, Lee, E, Lejbkowicz, F, Lilyquist, J, Lindblom, A, Lindstrom, S, Lissowska, J, Lo, W-Y, Loibl, S, Long, J, Lubinski, J, Lux, MP, MacInnis, RJ, Maishman, T, Makalic, E, Kostovska, IM, Mannermaa, A, Manoukian, S, Margolin, S, Martens, JWM, Martinez, ME, Mavroudis, D, McLean, C, Meindl, A, Menon, U, Middha, P, Miller, N, Moreno, F, Mulligan, AM, Mulot, C, Munoz-Garzon, VM, Neuhausen, SL, Nevanlinna, H, Neven, P, Newman, WG, Nielsen, SF, Nordestgaard, BG, Norman, A, Offit, K, Olson, JE, Olsson, H, Orr, N, Pankratz, VS, Park-Simon, T-W, Perez, JIA, Perez-Barrios, C, Peterlongo, P, Peto, J, Pinchev, M, Plaseska-Karanfilska, D, Polley, EC, Prentice, R, Presneau, N, Prokofyeva, D, Purrington, K, Pylkas, K, Rack, B, Radice, P, Rau-Murthy, R, Rennert, G, Rennert, HS, Rhenius, V, Robson, M, Romero, A, Ruddy, KJ, Ruebner, M, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmidt, DF, Schmutzler, RK, Schneeweiss, A, Schoemaker, MJ, Schumacher, F, Schuermann, P, Schwentner, L, Scott, C, Scott, RJ, Seynaeve, C, Shah, M, Sherman, ME, Shrubsole, MJ, Shu, X-O, Slager, S, Smeets, A, Sohn, C, Soucy, P, Southey, MC, Spinelli, JJ, Stegmaier, C, Stone, J, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Taylor, JA, Terry, MB, Thoene, K, Tollenaar, RAEM, Tomlinson, I, Truong, T, Tzardi, M, Ulmer, H-U, Untch, M, Vachon, CM, van Veen, EM, Vijai, J, Weinberg, CR, Wendt, C, Whittemore, AS, Wildiers, H, Willett, W, Winqvist, R, Wolk, A, Yang, XR, Yannoukakos, D, Zhang, Y, Zheng, W, Ziogas, A, Clarke, C, Balleine, R, Baxter, R, Braye, S, Carpenter, J, Dahlstrom, J, Forbes, J, Lee, CS, Marsh, D, Morey, A, Pathmanathan, N, Scott, R, Simpson, P, Spigelman, A, Wilcken, N, Yip, D, Zeps, N, Sexton, A, Dobrovic, A, Christian, A, Trainer, A, Fellows, A, Shelling, A, De Fazio, A, Blackburn, A, Crook, A, Meiser, B, Patterson, B, Saunders, C, Hunt, C, Amor, D, Ortega, DG, Edkins, E, Salisbury, E, Haan, E, Macrea, F, Farshid, G, Lindeman, G, Trench, G, Mann, G, Giles, G, Gill, G, Thorne, H, Campbell, I, Hickie, I, Caldon, L, Winship, I, Cui, J, Flanagan, J, Kollias, J, Visvader, J, Taylor, J, Burke, J, Saunus, J, Forbs, J, Hopper, J, Beesley, J, Kirk, J, French, J, Tucker, K, Wu, K, Phillips, K, Forrest, L, Lipton, L, Andrews, L, Lobb, L, Walker, L, Kentwell, M, Spurdle, M, Cummings, M, Gleeson, M, Harris, M, Jenkins, M, Young, MA, Delatycki, M, Wallis, M, Burgess, M, Brown, M, Southey, M, Bogwitz, M, Field, M, Friedlander, M, Gattas, M, Saleh, M, Aghmesheh, M, Hayward, N, Pachter, N, Cohen, P, Duijf, P, James, P, Fong, P, Butow, P, Williams, R, Kefford, R, Simard, J, Balleine, R-M, Dawson, S-J, Lok, S, O'connell, S, Greening, S, Nightingale, S, Edwards, S, Fox, S, McLachlan, S-A, Lakhani, S, Dudding, T, Antill, Y, Sahlberg, KK, Ottestad, L, Karesen, R, Schlichting, E, Holmen, MM, Sauer, T, Haakensen, V, Engebraten, O, Naume, B, Fossa, A, Kiserud, CE, Reinertsen, K, Helland, A, Riis, M, Geisler, J, Dunning, AM, Thompson, DJ, Chenevix-Trench, G, Chang-Claude, J, Schmidt, MK, Hall, P, Milne, RL, Pharoah, PDP, Antoniou, AC, Chatterjee, N, Kraft, P, Garcia-Closas, M, and Easton, DF
- Abstract
Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.
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- 2019
12. Adalimumab as first-line anti-TNF treatment in pediatric Crohn's disease
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Martín-de-Carpi J, Navas-Lopez, V, Navalon-Rubio, M, Llerena-Santa-Cruz, E, Ortega, DG, Varea V, and Sierra-Salinas, C
- Published
- 2014
13. Manuscript Clarification.
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Ortega DG and Housh TJ
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- 2025
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14. Cross-Validation of Equations for Estimating 1 Repetition Maximum From Repetitions to Failure for the Bench Press and Leg Extension.
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Roberts TD, Smith RW, Arnett JE, Ortega DG, Schmidt RJ, and Housh TJ
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- Humans, Male, Young Adult, Muscle, Skeletal physiology, Reproducibility of Results, Weight Lifting physiology, Muscle Strength physiology, Leg physiology, Resistance Training methods
- Abstract
Abstract: Roberts, TD, Smith, RW, Arnett, JE, Ortega, DG, Schmidt, RJ, and Housh, TJ. Cross-validation of equations for estimating 1 repetition maximum from repetitions to failure for the bench press and leg extension. J Strength Cond Res 39(2): e96-e105, 2025-Eighteen previously published equations (EQs) that estimate 1 repetition maximum (1RM) from repetitions to failure (RTF) were cross-validated for the bench press (BP) and leg extension (LE) movements. Forty-three recreationally active men (age: 20.58 ± 1.47 years; body mass [BM]: 81.66 ± 13.65 kg) completed a 1RM test and RTF at 80% of the 1RM test for the LE, and 39 of the 43 men (age: 20.61 ± 1.48 years; BM: 83.58 ± 12.73 kg) completed the same tests for the BP. The EQs were categorized as generic (the source did not indicate its applicability for a specific movement) or movement-specific (BP-specific and LE-specific EQs). The generic EQs were cross-validated for both movements, whereas the BP-specific and LE-specific EQs were cross-validated for their respective movements only. The cross-validation criteria included calculations of the constant error (CE) (mean differences between estimated and measured 1RM), Pearson Correlation Coefficient, standard error of the estimate, and total error. The level of significance was set at p ≤ 0.05. After the initial cross-validation analyses of the previously published EQs, the most accurate EQs were modified by subtracting their cross-validation CE from the original EQ to improve their accuracy for estimating BP and LE 1RM by eliminating systematic error. The modified EQs were then cross-validated using the same statistical procedures. Based on the cross-validation analyses, we recommend the following EQs: BP 1RM = (RTF 0.1 × weight) + 1.49 and LE 1RM = (RTF 0.1 × weight) + 1.06 using weights that result in 4-10 RTF., (Copyright © 2024 National Strength and Conditioning Association.)
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- 2025
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15. Perceived Factors That Contributed to Task Termination during Fatiguing Tasks Anchored to Perceptual Intensities.
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Ortega DG, Smith RW, Arnett JE, Neltner TJ, Roberts TD, Schmidt RJ, and Housh TJ
- Abstract
This study examined the effects of sustained, isometric forearm flexion tasks anchored to ratings of perceived exertion of 2 (RPE2
FT ) and 8 (RPE8FT ) on the patterns of fatigue-induced changes in torque and neuromuscular responses, time to task failure (TTF), performance fatigability (% decline in maximal voluntary isometric contraction [MVIC]), and perceived factors that contributed to task termination. Twelve men (mean ± SD: age = 20.9 ± 2.2 yrs) performed MVICs before and after the tasks and completed post-test questionnaires (PTQ). Data were analyzed using polynomial regression analyses, dependent t -tests, Spearman's rank order correlations, and Wilcoxon signed rank tests. The RPE8FT had greater ( p < 0.001) performance fatigability than the RPE2FT , despite no difference ( p > 0.05) in TTF. During both tasks, there were significant ( p ≤ 0.05) composite linear decreases for torque, electromyographic amplitude, and neuromuscular efficiency, and substantial individual variability in the neuromuscular responses. There were no significant ( p > 0.05) associations among the perceived factors and TTF or performance fatigability. Thus, there were RPE-specific differences in performance fatigability, but not TTF or the composite patterns of changes in torque and neuromuscular responses. In addition, in most cases, the individual neuromuscular, but not torque, patterns of responses were RPE-specific. Furthermore, the perceived factors assessed by the PTQ were not related to TTF or performance fatigability.- Published
- 2024
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16. Advancements and challenges in developing in vivo CAR T cell therapies for cancer treatment.
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Bui TA, Mei H, Sang R, Ortega DG, and Deng W
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- Humans, Animals, Genetic Vectors genetics, Genetic Vectors administration & dosage, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell immunology, Neoplasms therapy, Neoplasms immunology, Neoplasms genetics, Immunotherapy, Adoptive methods, Receptors, Chimeric Antigen genetics, Receptors, Chimeric Antigen immunology, T-Lymphocytes immunology, T-Lymphocytes metabolism
- Abstract
The Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a ground-breaking immunotherapeutic approach in cancer treatment. To overcome the complexity and high manufacturing cost associated with current ex vivo CAR T cell therapy products, alternative strategies to produce CAR T cells directly in the body have been developed in recent years. These strategies involve the direct infusion of CAR genes via engineered nanocarriers or viral vectors to generate CAR T cells in situ. This review offers a comprehensive overview of recent advancements in the development of T cell-targeted CAR generation in situ. Additionally, it identifies the challenges associated with in vivo CAR T method and potential strategies to overcome these issues., Competing Interests: Declaration of interests The authors report no conflicts of interest in this work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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17. Are performance and perceived fatigability dependent on the anchor scheme of fatiguing isometric tasks in men?
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Ortega DG, Smith RW, Arnett JE, Neltner TJ, Schmidt RJ, Johnson GO, and Housh TJ
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- Humans, Male, Young Adult, Torque, Forearm physiology, Perception physiology, Adult, Muscle, Skeletal physiology, Muscle Fatigue physiology, Isometric Contraction physiology, Electromyography, Physical Exertion physiology
- Abstract
Background: Ratings of perceived exertion (RPE) can be used to regulate exercise intensity. This study examined the effect of anchor scheme on performance fatigability and neuromuscular responses following fatiguing forearm flexion tasks., Methods: Twelve men (age 20.9±2.2 years; height 179.8±5.3 cm; body mass 80.2±9.9 kg) performed sustained, isometric forearm flexion tasks to failure anchored to RPE=6 (RPEFT) and the torque (TRQFT) that corresponded to RPE=6. Pre-test and post-test maximal voluntary isometric contractions (MVIC) were performed to quantify changes in the amplitude (AMP) and mean power frequency (MPF) of the electromyographic (EMG) and mechanomyographic (MMG) signals. Neuromuscular efficiency (NME) was calculated by dividing normalized torque by normalized EMG AMP. A dependent t-test was used to assess the mean difference for time to task failure (TTF). Repeated measures ANOVAs were used to compare mean differences for performance fatigability and normalized neuromuscular parameters., Results: The RPEFT had a greater TTF than the TRQFT (P<0.001). MVIC and NME decreased from pre-test to post-test following the RPEFT and TRQFT (P<0.05) with no differences between anchor schemes. Following the TRQFT, normalized EMG MPF decreased from pre-test to post-test (P=0.004). Following the RPEFT, normalized MMG MPF increased from pre-test to post-test (P=0.021). There were no changes in normalized EMG AMP or MMG AMP (P>0.05)., Conclusions: These findings indicated anchor scheme-specific neuromuscular responses and TTF, despite no difference in performance fatigability. Furthermore, performance fatigability was likely due to peripheral fatigue (based on normalized EMG MPF and NME) following the TRQFT, but peripheral and central fatigue (based on normalized MMG MPF and NME) following the RPEFT.
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- 2024
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18. The effects of sustained, low- and high-intensity isometric tasks on performance fatigability and the perceived responses that contributed to task termination.
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Smith RW, Ortega DG, Arnett JE, Neltner TJ, Schmidt RJ, Johnson GO, Weir JP, and Housh TJ
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- Humans, Male, Young Adult, Muscle, Skeletal physiology, Perception physiology, Adult, Torque, Muscle Fatigue physiology, Isometric Contraction physiology, Physical Exertion physiology
- Abstract
Purpose: The present study examined the effects of sustained, isometric low- versus high-intensity tasks on time to task failure (TTF), performance fatigability (PF), ratings of perceived exertion (RPE), and the perceived causes of task termination from a post-test questionnaire (PTQ)., Methods: Ten men (mean ± SD: age = 21.1 ± 2.3 years; height = 180.2 ± 5.7 cm; body mass = 79.5 ± 8.8 kg) performed maximal voluntary isometric contractions (MVICs) before and after fatiguing, isometric forearm flexion tasks anchored to the torque corresponding to RPE values of 2 (TRQ2FT = 23.8 ± 7.1 N·m) and 8 (TRQ8FT = 60.9 ± 11.4 N·m). In addition, the subjects completed a PTQ which surveyed whether the perceived sensations of fatigue or pain, and/or the psychological factors of loss of focus and motivation contributed to the decision to terminate the task. Repeated measures ANOVAs, Wilcoxon-Signed Rank tests, and Spearman's Rank-Order Correlations were used to analyze the data., Results: Across the fatiguing tasks, there were similar decreases in MVIC torque (95.2 ± 20.3 vs. 68.9 ± 15.6 N·m; p < 0.001) and RPE values (p = 0.122) at task failure for TRQ2FT (7.4 ± 2.7) and TRQ8FT (8.9 ± 1.0), but a longer (p = 0.005) TTF for the TRQ2FT (245.0 ± 177.0 s) than TRQ8FT (36.8 ± 11.1 s)., Conclusions: Despite reaching task failure, the subjects were able to perform MVICs that were 100-300% greater than the target torque values within seconds of terminating the tasks. Thus, we hypothesized that task failure was not caused by an inability to produce sufficient torque to sustain the tasks, but rather an unwillingness to continue the task., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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19. The Effects of Anchoring a Fatiguing Forearm Flexion Task to a High vs. Low Rating of Perceived Exertion on Torque and Neuromuscular Responses.
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Ortega DG, Housh TJ, Smith RW, Arnett JE, Neltner TJ, Schmidt RJ, and Johnson GO
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- Humans, Male, Young Adult, Perception physiology, Adult, Torque, Forearm physiology, Electromyography, Isometric Contraction physiology, Physical Exertion physiology, Muscle Fatigue physiology, Muscle, Skeletal physiology
- Abstract
Abstract: Ortega, DG, Housh, TJ, Smith, RW, Arnett, JE, Neltner, TJ, Schmidt, RJ, and Johnson, GO. The effects of anchoring a fatiguing forearm flexion task to a high versus low rating of perceived exertion on torque and neuromuscular responses. J Strength Cond Res 38(5): e219-e225, 2024-This study examined the torque and neuromuscular responses following sustained, isometric, forearm flexion tasks anchored to 2 ratings of perceived exertion (RPE). Nine men (mean ± SD: age = 21.0 ± 2.4 years; height = 179.5 ± 5.1 cm; body mass = 79.6 ± 11.4 kg) completed maximal voluntary isometric contractions (MVIC) before and after sustained, isometric, forearm flexion tasks to failure anchored to RPE = 2 and RPE = 8. The amplitude (AMP) and mean power frequency (MPF) of the electromyographic (EMG) signal were recorded from the biceps brachii. Normalized torque was divided by normalized EMG AMP to calculate neuromuscular efficiency (NME). A dependent t-test was used to assess the mean difference for time to task failure (TTF). Repeated-measures analysis of variances was used to compare mean differences for MVIC and normalized neuromuscular parameters. There was no significant difference in TTF between RPE = 2 and RPE = 8 (p = 0.713). The MVIC decreased from pretest to posttest at RPE = 2 (p = 0.009) and RPE = 8 (p = 0.003), and posttest MVIC at RPE = 8 was less than that at RPE = 2 (p < 0.001). In addition, NME decreased from pretest to posttest (p = 0.008). There was no change in normalized EMG AMP or EMG MPF (p > 0.05). The current findings indicated that torque responses were intensity specific, but TTF and neuromuscular responses were not. Furthermore, normalized EMG AMP and EMG MPF remained unchanged but NME decreased, likely due to peripheral fatigue and excitation-contraction coupling failure. Thus, this study provides information regarding the neuromuscular responses and mechanisms of fatigue associated with tasks anchored to RPE, which adds to the foundational understanding of the relationship between resistance exercise and the perception of fatigue., (Copyright © 2023 National Strength and Conditioning Association.)
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- 2024
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20. Sitting Less, Recovering Faster: Investigating the Relationship between Daily Sitting Time and Muscle Recovery following Intense Exercise: A Pilot Study.
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Rodden J, Ortega DG, and Costa PB
- Abstract
(1) There is growing concern surrounding the adverse effects of prolonged sitting on health, yet its impact on post-exercise recovery remains relatively unexplored. This study aimed to better understand the potential influence of habitual prolonged sitting on recovery time and the unfavorable impact prolonged sitting may have on time to recovery, as assessed by muscle damage and inflammatory markers and an isokinetic dynamometer. (2) Nine college-age men (mean age ± SD = 22.1 ± 3.1 years, body mass = 80.9 ± 15.7 kg, height = 171 ± 9.0 cm, Body Mass Index (BMI) = 27.6 ± 4.9 kg·m
2 ) participated in an exhaustive exercise protocol. Creatine Kinase (CK), Myoglobin (Mb), C-Reactive Protein (CRP), White Blood Cell Count (WBC), Peak Torque (PT), and muscle soreness were measured at baseline and 0, 24, 48, and 72 h post-exercise. Dietary and exercise logs were maintained during the 5-day testing procedure. (3) No significant differences were observed in muscle damage markers (CK [ p = 0.068] and Mb [ p = 0.128]), inflammatory markers (CRP [ p = 0.814] and WBC [ p = 0.140]), or PT [ p = 0.255]) at any time point. However, a significant positive correlation was found between daily sitting time and the percent increase in CK concentration from 0 h to 72 h ( r = 0.738, p = 0.023). Strong correlations were also noted between prolonged sitting and percent change in Mb concentration at 48 h ( r = 0.71, p = 0.033) and 72 h ( r = 0.889, p = 0.001). There was a significant two-way interaction for time × velocity ( p = 0.043) for PT with a simple main effect for time at 60°·s-1 ( p = 0.038). No significant associations were detected between daily carbohydrate or protein intake and recovery markers ( p > 0.05). (4) The findings suggest minimizing daily sitting time may expedite and potentially aid muscle recovery after an intense exercise bout, although further research is warranted to validate these findings.- Published
- 2024
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21. Effects of a Sustained, Isometric Forearm Flexion Task to Failure on Torque and Neuromuscular Responses at 3 Elbow Joint Angles.
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Ortega DG, Housh TJ, Smith RW, Arnett JE, Neltner TJ, Anders JPV, Schmidt RJ, and Johnson GO
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- Humans, Female, Adolescent, Young Adult, Adult, Forearm, Torque, Muscle, Skeletal physiology, Isometric Contraction physiology, Electromyography methods, Elbow Joint
- Abstract
Abstract: Ortega, DG, Housh, TJ, Smith, RW, Arnett, JE, Neltner, TJ, Anders, JPV, Schmidt, RJ, and Johnson, GO. The effects of a sustained, isometric forearm flexion task to failure on torque and neuromuscular responses at 3 elbow joint angles. J Strength Cond Res 38(1): e25-e33, 2024-This study examined the effects of a sustained, isometric forearm flexion task anchored to torque to task failure on maximal voluntary isometric contraction (MVIC) and neuromuscular responses at 3 elbow joint angles. Eleven women (mean ± SD: age = 20.8 ± 2.7 years, height = 169.3 ± 7.4 cm, body mass = 67.7 ± 6.9 kg) performed two 3s forearm flexion MVICs at elbow joint angles (JAs) of 75°, 100°, and 125° before and after a sustained, isometric forearm flexion task to failure at a fatiguing joint angle of 100° anchored to a torque value that corresponded to a rating of perceived exertion of 8 (RPE = 8). The amplitude (AMP) and mean power frequency (MPF) of the electromyographic (EMG) and mechanomyographic (MMG) signals were recorded from the biceps brachii. Repeated-measures ANOVAs were used to compare mean differences for MVIC and neuromuscular parameters. Collapsed across JAs, MVIC (p < 0.001) and EMG MPF (p = 0.006) pretest values were greater than posttest values. Collapsed across time, EMG MPF at JA75 was greater than JA100 (p < 0.001) and JA125 (p < 0.001), and JA100 was greater (p = 0.007) than JA125. For EMG AMP, there was a fatigue-induced decrease at JA75 (p = 0.003). For neuromuscular efficiency (NME = normalized torque/normalized EMG AMP), there were decreases from pretest to posttest at JA100 (p = 0.002) and JA125 (p = 0.008). There were no significant interactions or main effects for MMG AMP and MMG MPF. From these findings, it was hypothesized that the decline in MVICs at JA75, JA100, and JA125 was due to fatigue-induced metabolic perturbations that resulted in JA-specific neuromuscular responses. Thus, neuromuscular parameters may provide insight into the JA-specific mechanisms of fatigue., (Copyright © 2023 National Strength and Conditioning Association.)
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- 2024
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22. Effects of High-Intensity, Eccentric-Only Muscle Actions on Serum Biomarkers of Collagen Degradation and Synthesis.
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Neltner TJ, Sahoo PK, Smith RW, Anders JPV, Arnett JE, Ortega DG, Schmidt RJ, Johnson GO, Natarajan SK, and Housh TJ
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- Male, Humans, Young Adult, Adult, Biomarkers, Collagen, Muscles, Exercise, Myalgia
- Abstract
Abstract: Neltner, TJ, Sahoo, PK, Smith, RW, Anders, JPV, Arnett, JE, Ortega, DG, Schmidt, RJ, Johnson, GO, Natarajan, SK, and Housh, TJ. Effects of high-intensity, eccentric-only muscle actions on serum biomarkers of collagen degradation and synthesis. J Strength Cond Res 37(9): 1729-1737, 2023-The purpose of this study was to examine the effects of high-intensity, eccentric-only muscle actions of the leg extensors on (a) serum biomarkers of collagen degradation (hydroxyproline [HYP] and C-terminal telopeptide of type I collagen [C1M]) and synthesis (pro-c1α1) and (b) the time course of changes in maximal voluntary isometric contraction (MVIC) and ratings of muscle soreness after the eccentric-only exercise bout. Twenty-five recreationally active men (mean ± SD: age = 21.2 ± 2.0 years) completed 5 sets of 10 bilateral, eccentric-only dynamic constant external resistance muscle actions of the leg extensors at a load of 110% of their concentric leg extension 1 repetition maximum. Analysis of variances (p < 0.05) and a priori planned pairwise comparisons using Bonferroni corrected (p < 0.0167) paired t tests were used to examine mean changes in blood biomarkers from baseline to 48 hours postexercise as well as in MVIC and soreness ratings immediately, 24 hours, and 48 hours postexercise. There were increases in HYP (3.41 ± 2.37 to 12.37 ± 8.11 μg·ml-1; p < 0.001) and C1M (2.50 ± 1.05 to 5.64 ± 4.89 μg·L-1; p = 0.003) from preexercise to 48 hours postexercise, but no change in pro-c1α1. Maximal voluntary isometric contraction declined immediately after the exercise bout (450.44 ± 72.80 to 424.48 ± 66.67 N·m; p = 0.002) but recovered 24 hours later, whereas soreness was elevated immediately (6.56 ± 1.58; p < 0.001), 24 hours (3.52 ± 1.53; p < 0.001), and 48 hours (2.60 ± 1.32; p = 0.001) postexercise. The eccentric-only exercise bout induced increases in collagen degradation but had no effect on collagen synthesis. These findings provide information for clinicians to consider when prescribing exercise after an acute injury or surgery., (Copyright © 2023 National Strength and Conditioning Association.)
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- 2023
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23. Performance Fatigability and Neuromuscular Responses Are Not Joint Angle Specific Following a Sustained Isometric Forearm Flexion Task Anchored to a High Perceptual Intensity in Women.
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Arnett JE, Smith RW, Neltner TJ, Anders JPV, Ortega DG, Housh TJ, Schmidt RJ, and Johnson GO
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- Female, Humans, Adolescent, Young Adult, Adult, Isometric Contraction, Torque, Forearm, Upper Extremity
- Abstract
Objectives: To examine the effects of joint angle (JA) on maximal voluntary isometric contractions (MVIC) and neuromuscular responses following a sustained, isometric forearm flexion task anchored to a rating of perceived exertion (RPE) of 8 (RPE=8)., Methods: Nine women (age: 20.7±2.9 yrs; height: 168.8±7.2 cm; body mass: 66.3±6.8 kg) performed 2,3s forearm flexion MVICs at JAs of 75°, 100°, and 125° prior to and following a sustained, isometric forearm flexion task anchored to RPE=8 to task failure (torque reduced to zero) at JA100. Electromyographic (EMG) and mechanomyographic (MMG) signals were recorded from the biceps brachii., Results: The MVIC at JA100 (collapsed across Time) was significantly greater (p<0.05) than JA75 and JA125. The pre-test MVIC was significantly greater (p<0.001) than the post-test. For EMG amplitude (AMP) and EMG mean power frequency (MPF), pre-test values were significantly greater (p<0.05) than the post-test values, with no differences between JAs. For MMG AMP and MMG MPF, there were no significant (p>0.05) differences between Time or JAs. Pre-test neuromuscular efficiency (normalized MVIC/normalized EMG AMP) was significantly greater (p=0.005) than post-test., Conclusion: Following a sustained, isometric forearm flexion task anchored to RPE=8 at JA100, the fatigue-induced MVIC and neuromuscular responses were not affected by JA., Competing Interests: The authors have no conflict of interest.
- Published
- 2023
24. Effects of a Tart Cherry Supplement on Recovery from Exhaustive Exercise.
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Ortega DG, Coburn JW, Galpin AJ, and Costa PB
- Abstract
The aim of this study was to investigate the effects of a tart cherry supplement on recovery from exercise-induced muscle damage. Seventeen recreationally active women (mean age ± SD = 22.2 ± 3.3 years, height = 162.0 ± 6.0 cm, body mass = 65.1 ± 11.1 kg, BMI = 24.7 ± 3.5 kg·m
2 ) supplemented with 1000 mg of concentrated tart cherry or a placebo for eight consecutive days. An overload protocol of 8 sets of 10 repetitions of maximal effort concentric and eccentric muscle actions of the leg extensors at a velocity of 60°·s-1 was performed on the fourth day of supplementation. Testing sessions consisted of a muscle function test (MFT) to examine pre- and post-testing peak torque, peak power, total work, time-to-peak torque, mean power, muscle activation of the quadriceps, and muscle soreness at baseline and post-testing at 0 h, 24 h, 48 h, and 72 h. A second trial of testing was repeated two weeks later using the opposite supplement to the one assigned for the first trial. No significant interaction for time × condition × velocity ( p = 0.916) and no significant main effect for condition ( p = 0.557) were demonstrated for peak torque. However, there were main effects for time and velocity for concentric quadriceps peak torque ( p < 0.001). For muscle soreness, there was no two-way interaction for time x condition ( p > 0.05) and no main effect for condition ( p > 0.05), but there was a main effect for time ( p < 0.001). In conclusion, a tart cherry supplement did not attenuate losses in isokinetic muscle peak torque, peak power, total work, time-to-peak torque, muscle soreness, or quadriceps muscle activation.- Published
- 2023
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25. Fatiguing Joint Angle Does Not Influence Torque and Neuromuscular Responses Following Sustained, Isometric Forearm Flexion Tasks Anchored to Perceptual Intensity in Men.
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Ortega DG, Housh TJ, Smith RW, Arnett JE, Neltner TJ, Anders JPV, Schmidt RJ, and Johnson GO
- Abstract
This study examined the effects of joint angle (JA) on maximal voluntary isometric contraction (MVIC) and neuromuscular responses following fatiguing tasks anchored to RPE. Nine men (mean ± SD: age = 20.7 ± 1.2 yrs) performed forearm flexion MVICs at elbow JAs of 75° and 125° before and after sustained, isometric forearm flexion tasks to failure at fatiguing joint angles (FJA) of 75° and 125° anchored to RPE = 8. The amplitude and frequency of the electromyographic and mechanomyographic signals were recorded. Neuromuscular efficiency was calculated by dividing normalized torque by normalized electromyographic amplitude. A dependent t -test was used to assess the mean difference for time to task failure (TTF) between FJA. Repeated measure ANOVAs were used to assess mean differences for pre-test to post-test MVIC and neuromuscular responses. There was no significant difference between FJA for TTF ( p = 0.223). The MVIC (collapsed across FJA and MVIC JA) decreased from pre-test to post-test (51.1 ± 5.0 vs. 45.3 ± 5.6 Nm, p < 0.001). Normalized neuromuscular parameters remained unchanged ( p > 0.05). The FJA resulted in similar torque and neuromuscular responses, and the decreases in MVIC were not tracked by changes in the neuromuscular parameters. Thus, the neuromuscular parameters were not sensitive to fatigue, and pre-test to post-test measures may be compared between different FJA.
- Published
- 2023
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26. Utilizing the RPE-Clamp model to examine interactions among factors associated with perceived fatigability and performance fatigability in women and men.
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Smith RW, Housh TJ, Arnett JE, Anders JPV, Neltner TJ, Ortega DG, Schmidt RJ, and Johnson GO
- Subjects
- Male, Adult, Humans, Female, Electromyography, Upper Extremity, Isometric Contraction physiology, Torque, Muscle, Skeletal physiology, Muscle Fatigue physiology
- Abstract
Purpose: The purpose of the present study was to examine the interactions between perceived fatigability and performance fatigability in women and men by utilizing the RPE-Clamp model to assess the fatigue-induced effects of a sustained, isometric forearm flexion task anchored to RPE = 8 on time to task failure (TTF), torque, and neuromuscular responses., Methods: Twenty adults (10 men and 10 women) performed two, 3 s forearm flexion maximal voluntary isometric contractions (MVICs) followed by a sustained, isometric forearm flexion task anchored to RPE = 8 using the OMNI-RES (0-10) scale at an elbow joint angle of 100°. Electromyographic amplitude (EMG AMP) was recorded from the biceps brachii. Torque and EMG AMP values resulting from the sustained task were normalized to the pretest MVIC. Neuromuscular efficiency was defined as NME = normalized torque/normalized EMG AMP. Mixed factorial ANOVAs and Bonferroni corrected dependent t tests and independent t tests were used to examine differences across time and between sex for torque and neuromuscular parameters., Results: There were no differences between the women and men for the fatigue-induced decreases in torque, EMG AMP, or NME, and the mean decreases (collapsed across sex) were 50.3 ± 8.6 to 2.8 ± 2.9% MVIC, 54.7 ± 12.0 to 19.6 ± 5.3% MVIC, and 0.94 ± 0.19 to 0.34 ± 0.16, respectively. Furthermore, there were no differences between the women and men for TTF (251.8 ± 74.1 vs. 258.7 ± 77.9 s)., Conclusion: The results suggested that the voluntary reductions in torque to maintain RPE and the decreases in NME were likely due to group III/IV afferent feedback from peripheral fatigue that resulted in excitation-contraction coupling failure., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2023
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27. Robotic Simultaneous Repair of Rectovesical Fistula With Vesicourethral Anastomotic Stricture after Radical Prostatectomy: Step-by-Step Technique and Outcomes.
- Author
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Sayegh AS, La Riva A, Perez LC, Medina LG, Poncel J, Ortega DG, Lizana MA, Forsyth E, and Sotelo R
- Subjects
- Male, Humans, Aged, Constriction, Pathologic etiology, Constriction, Pathologic surgery, Retrospective Studies, Anastomosis, Surgical adverse effects, Prostatectomy adverse effects, Prostatectomy methods, Robotic Surgical Procedures adverse effects, Urinary Bladder Fistula
- Abstract
Objective: To report our experience and outcomes using a novel robotic technique for the simultaneous repair of rectovesical fistula (RVF) with vesicourethral anastomotic stricture (VUAS) after radical prostatectomy (RP)., Methods: Between 2019 and 2021, four consecutive patients who underwent robotic-assisted simultaneous repair of RVF with concurrent VUAS after RP were retrospectively reviewed. Baseline characteristics and perioperative outcomes were examined and reported. Complications were graded using the modified Clavien-Dindo classification system and the European Association of Urology Complications Panel Assessment and Recommendations., Results: Four cases with a median age of 68.5 (63.3-72.3) years were treated. Interposition omentum flaps were used in all our cases. One case had perineal urethral mobilization to reach healthy urethral margins and tension-free vesicourethral anastomosis. Surgeries were uneventful, with no intraoperative complications reported. Median operative time, estimated blood loss, and length of hospital stay were 370 (291.3-453) minutes, 255 (175-262.5) mL, and 2.5 (2-3) days, respectively. Median Jackson-Pratt drains, Double-J stents and Foley catheter removal days were 6 (6-10), 38 (32-43), and 30 (27-41) days, respectively. No postoperative complications were reported. The median follow-up time was 16.25 (12-26) months, and no fistula recurrence was shown., Conclusion: Robotic-assisted laparoscopic repair could represent an effective approach for the simultaneous repair of RVF with concomitant VUAS. More studies and management standardization are needed to assess the role of the robotic platform in the simultaneous repair of RVF with VUAS after radical prostatectomy., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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28. The Effects of Anchor Schemes on Performance Fatigability, Neuromuscular Responses and the Perceived Sensations That Contributed to Task Termination.
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Smith RW, Housh TJ, Arnett JE, Anders JPV, Neltner TJ, Ortega DG, Schmidt RJ, and Johnson GO
- Abstract
The present study examined the effect of anchor schemes on the time to task failure (TTF), performance fatigability, neuromuscular responses, and the perceived sensations that contributed to task termination following the sustained, isometric forearm flexion tasks. Eight women completed sustained, isometric forearm flexion tasks anchored to RPE = 8 (RPEFT) and the torque (TRQFT) that corresponded to RPE = 8. The subjects performed pre-test and post-test maximal isometric contractions to quantify performance fatigability and changes in electromyographic amplitude (EMG AMP) and neuromuscular efficiency (NME). In addition, the subjects completed a post-test questionnaire (PTQ) to quantify the contributions of perceived sensations to task termination. Repeated measure ANOVAs were used to assess the mean differences for TTF, performance fatigability, and neuromuscular responses. Wilcoxon Signed Rank Tests were used to assess the differences between anchor schemes for the average values from the PTQ item scores. For TTF, the RPEFT was longer than the TRQFT (174.9 ± 85.6 vs. 65.6 ± 68.0 s; p = 0.006). Collapsed across the anchor scheme, there were decreases in torque (23.7 ± 5.5 Nm vs. 19.6 ± 4.9 Nm; p < 0.001) and NME (1.00 ± 0.00 vs. 0.76 ± 0.15; p = 0.003). There were no significant ( p > 0.577) changes for EMG AMP. For the PTQ, there were no differences ( p > 0.05) between anchor schemes. There were, however, inter-individual differences in the response scores. The current findings indicated that performance fatigability was likely due to peripheral fatigue (based on NME), not central fatigue (based on EMG AMP). Furthermore, the use of a PTQ may serve as a simple tool to assess the contributions of perceived sensations to task termination.
- Published
- 2023
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29. Minimally Invasive Management of Post-treatment Rectovesical Fistulae.
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Medina LG, Riva A, Perez LC, Sayegh AS, Ortega DG, Rangel E, Hernandez AB, Lizana MA, Aponte HA, Sanchez A, Polotti CF, Cacciamani GE, and Sotelo R
- Subjects
- Male, Female, Humans, Aged, Retrospective Studies, Postoperative Complications etiology, Postoperative Complications surgery, Laparoscopy methods, Rectal Fistula surgery, Rectal Fistula etiology, Robotics
- Abstract
Objective: The aim of this study is to report our experience in minimally invasive management of rectovesical fistulae (RVFs). Materials and Methods: Between 2004 and 2021, 24 patients who underwent minimally invasive RVF repair by a single surgeon at 3 international institutions were retrospectively reviewed. Baseline demographic characteristics and perioperative and postoperative variables were collected. Complications were reported using the modified Clavien-Dindo Classification System and the European Association of Urology Complication Guidelines Panel Assessment and Recommendations. Fistula repair was defined as confirmation of fistula closure by imaging and complete resolution of fistula-related symptoms at the 12-month follow-up. Continuous variables are reported as medians and quartiles, whereas categorical variables are reported as frequencies and percentages. Results: Twenty-four patients with RVFs were treated: 22 males (91.7%) and 2 females with a median age of 66 (64.2-68) years. Twenty cases (83.3%) occurred postsurgery, three cases (12.5%) after surgery with combined radiotherapy, and one case (4.1%) after a combination of energy treatments. A robotic approach was performed in 19 patients (79%) and laparoscopic approach in 5 patients (21%). Ninety-six percent of patients had previous fecal diversions. No intraoperative complications were recorded. The median operative time was 180 (140-282) minutes, estimated blood loss was 50 (40-125) mL, and length of hospital stay was 2 (2-3) days. There were two Grade II complications and one Grade IIIb complication. All patients met criteria for repair. Conclusions: Minimally invasive management of RVFs is feasible. More studies are needed to assess the role of this approach among all RVF management options.
- Published
- 2023
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30. Variants Identified in the HOXC13 and HOXD13 Genes Suggest Association with Cervical Cancer in a Cohort of Mexican Women.
- Author
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Juárez-Rendón KJ, Castro-García MA, Prada-Ortega DG, Rivera G, Ruíz-Godoy LM, Enríquez-Cárcamo VI, and Reyes-Lopez MA
- Subjects
- Female, Humans, Base Sequence, Homeodomain Proteins genetics, Transcription Factors genetics, Genes, Homeobox, Uterine Cervical Neoplasms genetics
- Abstract
HOX genes have been associated with carcinogenesis. However, the molecular mechanism by which tumors are generated remains unclear. The HOXC13 and HOXD13 genes are of interest for their involvement in the development of genitourinary structures. The aim of this first study in the Mexican population was to search for and analyze variants in the coding region of the HOXC13 and HOXD13 genes in women with cervical cancer. Samples from Mexican women with cervical cancer and healthy women were sequenced (50/50). Allelic and genotypic frequencies were compared between groups. The functional impact of the proteins was determined with two bioinformatics servers (SIFT and PolyPhen-2), and the oncogenic potential of the identified nonsynonymous variants was determined using the CGI server. We identified five unreported gene variants: c.895C>A p.(Leu299Ile) and c.777C>T p.(Arg259Arg) in the HOXC13 gene and c.128T>A p.(Phe43Tyr), c.204G>A p.(Ala68Ala), and c.267G>A p.(Ser89Ser) in the HOXD13 gene. In this study, we suggest that the non-synonymous variants c.895C>A p.(Leu299Ile) and c.128T>A p.(Phe43Tyr) could represent a risk factor for the development of the disease, although additional studies in larger patient populations and in different ethnic groups are needed in order to support the results observed.
- Published
- 2023
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31. Cowper's gland syringocele in an adult: The great imitator.
- Author
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Ortega DG, Rojas EI, Lizana M, Poncel J, Rosenberg E, and Rosenberg S
- Abstract
Cowper's gland syringocele (CGS) is the cystic dilation of its duct. It is an uncommon urological condition and is thought to be more commonly encountered in pediatric urology. However, it is in adults that CGS poses a diagnostic challenge because of its "chameleon-like" clinical presentation that may masquerade multiple urological etiologies. In this population, where urological conditions are more prevalent, CGS may present as bladder outlet obstruction, recurrent urinary tract infections, gross hematuria, urinary retention, perineal pain, or abscess., (© 2022 The Authors.)
- Published
- 2022
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32. Minimally Invasive Management of Rectourethral Fistulae.
- Author
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Medina LG, Sayegh AS, La Riva A, Perez LC, Ortega DG, Rangel E, Hernandez AB, Lizana MA, Sanchez A, Polotti CF, Cacciamani GE, and Sotelo R
- Subjects
- Aged, Humans, Male, Postoperative Complications epidemiology, Retrospective Studies, Minimally Invasive Surgical Procedures adverse effects, Middle Aged, Rectal Fistula surgery, Urethral Diseases surgery, Urinary Fistula surgery
- Abstract
Objective: To report our experience and outcomes in minimally invasive management of rectourethral fistula (RUF)., Methods: From 2004 to 2021, 15 patients who underwent minimally invasive RUF repair by a single surgeon at 2 international institutions were retrospectively reviewed. Baseline demographic characteristics, perioperative, and postoperative data were collected. Complications were reported using the modified Clavien-Dindo Classification System and the European Association of Urology Complication Panel Assesment and Recommendations. Success was defined as complete resolution of fistula-related symptoms at 12-month follow-up along with confirmation of fistula closure by imaging or cystoscopy. Categorical variables were presented as frequencies and percentages whereas continuous variables were reported as median and quartiles., Results: Fifteen male patients with a median age of 71 (64-79.2) years were treated. Four cases (26.6%) occurred postsurgery, 8 cases (53.3%) occurred after energy treatments, and 3 cases (20%) after surgery combined with an energy treatment modality. A robotic and laparoscopic approach was performed in 9 (60%) and 6 (40%) patients, respectively. No intraoperative complications were reported. Median operative time was 264 (217.5-341) minutes, estimated blood loss was 175 (137.5-200) mL, and the length of hospital stay was 4 days. Nine postoperative complications were reported. All patients were followed-up for 12 months with no recurrence reported. All patients reached our criteria for successful RUF repair., Conclusions: Minimally invasive surgery could represent an efficient way to manage RUF in selected patients. More studies and treatment standardization are needed to assess the role of minimally invasive surgery in the management of RUF., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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33. Disentangling single-cell omics representation with a power spectral density-based feature extraction.
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Zandavi SM, Koch FC, Vijayan A, Zanini F, Mora FV, Ortega DG, and Vafaee F
- Subjects
- Single-Cell Analysis methods, Transcriptome
- Abstract
Emerging single-cell technologies provide high-resolution measurements of distinct cellular modalities opening new avenues for generating detailed cellular atlases of many and diverse tissues. The high dimensionality, sparsity, and inaccuracy of single cell sequencing measurements, however, can obscure discriminatory information, mask cellular subtype variations and complicate downstream analyses which can limit our understanding of cell function and tissue heterogeneity. Here, we present a novel pre-processing method (scPSD) inspired by power spectral density analysis that enhances the accuracy for cell subtype separation from large-scale single-cell omics data. We comprehensively benchmarked our method on a wide range of single-cell RNA-sequencing datasets and showed that scPSD pre-processing, while being fast and scalable, significantly reduces data complexity, enhances cell-type separation, and enables rare cell identification. Additionally, we applied scPSD to transcriptomics and chromatin accessibility cell atlases and demonstrated its capacity to discriminate over 100 cell types across the whole organism and across different modalities of single-cell omics data., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2022
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34. Upconversion nanoparticle-assisted single-molecule assay for detecting circulating antigens of aggressive prostate cancer.
- Author
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Chen Y, Shimoni O, Huang G, Wen S, Liao J, Duong HTT, Maddahfar M, Su QP, Ortega DG, Lu Y, Campbell DH, Walsh BJ, and Jin D
- Subjects
- Biomarkers, Humans, Leptin, Male, Vascular Endothelial Growth Factor A, Nanoparticles, Prostatic Neoplasms diagnosis
- Abstract
Sensitive and quantitative detection of molecular biomarkers is crucial for the early diagnosis of diseases like metabolic syndrome and cancer. Here we present a single-molecule sandwich immunoassay by imaging the number of single nanoparticles to diagnose aggressive prostate cancer. Our assay employed the photo-stable upconversion nanoparticles (UCNPs) as labels to detect the four types of circulating antigens in blood circulation, including glypican-1 (GPC-1), leptin, osteopontin (OPN), and vascular endothelial growth factor (VEGF), as their serum concentrations indicate aggressive prostate cancer. Under a wide-field microscope, a single UCNP doped with thousands of lanthanide ions can emit sufficiently bright anti-Stokes' luminescence to become quantitatively detectable. By counting every single streptavidin-functionalized UCNP which specifically labeled on each sandwich immune complex across multiple fields of views, we achieved the Limit of Detection (LOD) of 0.0123 ng/ml, 0.2711 ng/ml, 0.1238 ng/ml, and 0.0158 ng/ml for GPC-1, leptin, OPN and VEGF, respectively. The serum circulating level of GPC-1, leptin, OPN, and VEGF in a mixture of 10 healthy normal human serum was 25.17 ng/ml, 18.04 ng/ml, 11.34 ng/ml, and 1.55 ng/ml, which was within the assay dynamic detection range for each analyte. Moreover, a 20% increase of GPC-1 and OPN was observed by spiking the normal human serum with recombinant antigens to confirm the accuracy of the assay. We observed no cross-reactivity among the four biomarker analytes, which eliminates the false positives and enhances the detection accuracy. The developed single upconversion nanoparticle-assisted single-molecule assay suggests its potential in clinical usage for prostate cancer detection by monitoring tiny concentration differences in a panel of serum biomarkers., (© 2021 International Society for Advancement of Cytometry.)
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- 2022
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35. Complete testicular-epididymal dissociation presenting as adult chronic orchialgia.
- Author
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Ortega DG, Lizana M, Asanad K, and Samplaski MK
- Abstract
Complete testicular epididymal dissociations are exceedingly rare conditions where the epididymis and the vas deferens are completely dissociated from the testicle. We present the case of a 46-year-old male with a history of chronic, intermittent and severe left testicular pain who was found to have a complete testicular epididymal dissociation at the time of surgical exploration and bilateral orchidopexy. Microsurgical approximation of the tail of the epididymis to the tunica albuginea of the testis with reapproximating the muscularis of the spermatic cord to the epididymal appendage was performed with subsequent relief of symptoms., Competing Interests: This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors., (© 2022 Published by Elsevier Inc.)
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- 2022
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36. Prognostic Significance of the MAD1L1 1673 G: A Polymorphism in Ovarian Adenocarcinomas.
- Author
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Bandala-Jacques A, Hernández-Cruz IA, Castro-Hernández C, Díaz-Chávez J, Arriaga-Canon C, Barquet-Muñoz SA, Prada-Ortega DG, Cantú-de León D, and Herrera LA
- Subjects
- Adenocarcinoma mortality, Adolescent, Adult, Aged, Female, Humans, Middle Aged, Ovarian Neoplasms mortality, Prognosis, Retrospective Studies, Survival Rate, Young Adult, Adenocarcinoma genetics, Cell Cycle Proteins genetics, Ovarian Neoplasms genetics, Polymorphism, Single Nucleotide
- Abstract
Background: Ovarian cancer is the most lethal gynecologic cancer. Although most patients respond adequately to the first-line therapy, up to 85% experience a recurrence of disease, which carries a poor prognosis. Mitotic arrest deficiency 1 is a protein that helps in the assembly of the mitotic spindle assembly checkpoint by preventing anaphase until all chromatids are properly aligned. A single-nucleotide polymorphism in the MAD1L1 gene is prevalent in patients with advanced epithelial ovarian cancer and alters the way in which it responds to chemotherapy., Objective: The objective of the study was to study the relationship between the rs1801368 polymorphism of MAD1L1 and prognosis of ovarian adenocarcinoma., Methods: A total of 118 patients in whom the MAD1L1 gene was sequenced were analyzed using descriptive and comparative statistics., Results: Patients carrying the wild-type genotype had a higher distribution of early-stage disease. Having a MAD1L1 polymorphic allele increased the risk of being non-sensitive to chemotherapy. The median disease-free survival for patients with the wild-type MAD1L1 was 46.93 months, compared to 10.4 months for patients with at least one polymorphic allele., Conclusions: The rs1801368 polymorphism of MAD1L1 gene worsens prognosis in patients with ovarian adenocarcinoma. Traditional therapy for ovarian cancer might not be optimal in patients carrying this polymorphism.
- Published
- 2020
- Full Text
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37. Complete Remission of Advanced Gastric Cancer in Response to Chemotherapy With Docetaxel, Cisplatin and Capecitabine (dcx).
- Author
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Marroqui AJ, Ferrandiz CL, Escalante SM, Molla SB, and Ortega DG
- Abstract
We describe the case of a 60 year-old man with advanced gastric cancer. The patient started chemotherapy with a combination of docetaxel, cisplatin and capecitabine. In a radiological assessment after the third treatment cycle, a significant reduction of adenopathies and gastric wall thickening was observed. Partial remission was maintained until the end of the chemotherapy (6 cycles). The follow-up evaluations indicated the radiological remission was maintained and that there was a reduction of gastric wall thickening and normalisation of remote lymph nodes. After 43 months since the final treatment cycle, the patient remains progression-free.
- Published
- 2011
- Full Text
- View/download PDF
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