12 results on '"Linda T. Doan"'
Search Results
2. PI3K Promotes Basal Cell Carcinoma Growth Through Kinase-Induced p21 Degradation
- Author
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Rachel Y. Chow, Ung Seop Jeon, Taylor M. Levee, Gurleen Kaur, Daniel P. Cedeno, Linda T. Doan, and Scott X. Atwood
- Subjects
basal cell carcinoma ,hedgehog ,PI3K - AKT pathway ,p21 ,atypical PKCι ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Basal cell carcinoma (BCC) is a locally invasive epithelial cancer that is primarily driven by the Hedgehog (HH) pathway. Advanced BCCs are a critical subset of BCCs that frequently acquire resistance to Smoothened (SMO) inhibitors and identifying pathways that bypass SMO could provide alternative treatments for patients with advanced or metastatic BCC. Here, we use a combination of RNA-sequencing analysis of advanced human BCC tumor-normal pairs and immunostaining of human and mouse BCC samples to identify a PI3K pathway expression signature in BCC. Pharmacological inhibition of PI3K activity in BCC cells significantly reduces cell proliferation and HH signaling. However, treatment of Ptch1fl/fl; Gli1-CreERT2 mouse BCCs with the PI3K inhibitor BKM120 results in a reduction of tumor cell growth with no significant effect on HH signaling. Downstream PI3K components aPKC and Akt1 showed a reduction in active protein, whereas their substrate, cyclin-dependent kinase inhibitor p21, showed a concomitant increase in protein stability. Our results suggest that PI3K promotes BCC tumor growth by kinase-induced p21 degradation without altering HH signaling.
- Published
- 2021
- Full Text
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3. Gait Training in Patients Discharged to a Skilled Nursing Facility Following Total Joint Arthroplasty
- Author
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Brandon Haghverdian BSc, David Wright MSc, Linda T. Doan BSc, Dennis Tran BSc, and Ran Schwarzkopf MD, MSc
- Subjects
Orthopedic surgery ,RD701-811 ,Geriatrics ,RC952-954.6 - Abstract
Background: Expenditures for postacute care in total joint arthroplasty (TJA) have risen dramatically over recent decades. Therefore, efforts are underway to better identify cost savings in postacute rehabilitation centers, such as skilled nursing facilities (SNFs). The primary purpose of this study was to analyze gait training achievements in post-TJA patients in the interval between hospital discharge and the patients’ first 4 days at the SNF. Identification of potential losses in therapeutic progress may lead the way for improved patient care, outcomes, and cost savings. Our hypothesis is that patients discharged to an SNF will have a decline in gait achievements upon transfer from the hospital. Methods: A total of 68 patients who underwent TJA were included. The total distance ambulated during physical therapy (PT) was recorded for the last day of hospital therapy and the first 4 days at the SNF as well as the reported visual analog scale (VAS) pain scores. Results: There was a 73% decline in distance ambulated on SNF day 0 ( Hospital : 138.6 ft vs SNF : 37.9 ft; P < .001) and a 50% decline on SNF day 1 ( Hospital : 103.0 ft; SNF vs 51.1 ft; P < .001) compared to the last hospital session. There were no significant differences in distance walked on SNF days 3 and 4 relative to the last hospital session. The VAS pain scores did not significantly differ on SNF days 0 and 1 compared to the last hospital day but began to significantly decline on SNF day 3 ( Hospital: 4.9; SNF : 3.3; P = .02) and day 4 ( Hospital: 3.9; SNF : 2.3; P = .03). Conclusion: There was a significant decline in ambulatory proficiency in post-TJA patients on the day of and the day following hospital discharge to an SNF. These deficits cannot be attributed to heightened pain levels. Early and progressive ambulation is a recognized component of appropriate PT following TJA. This study therefore highlights the transition from hospital to SNF as a crucial and novel target for improvement in post-TJA care.
- Published
- 2016
- Full Text
- View/download PDF
4. Histologic Screening of Malignant Melanoma, Spitz, Dermal and Junctional Melanocytic Nevi Using a Deep Learning Model
- Author
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Alan N. Snyder, Dan Zhang, Steffen L. Dreesen, Christopher A. Baltimore, Dan R. Lopez-Garcia, Jake Y. Akers, Christopher L. Metts, James E. Madory, Peter D. Chang, Linda T. Doan, Dirk M. Elston, Manuel A. Valdebran, Feng Luo, and Jessica A. Forcucci
- Subjects
Diagnosis, Differential ,Nevus, Pigmented ,Deep Learning ,Skin Neoplasms ,Artificial Intelligence ,Nevus, Epithelioid and Spindle Cell ,Humans ,Pilot Projects ,Dermatology ,General Medicine ,Melanoma ,Pathology and Forensic Medicine - Abstract
The integration of an artificial intelligence tool into pathologists' workflow may lead to a more accurate and timely diagnosis of melanocytic lesions, directly patient care. The objective of this study was to create and evaluate the performance of such a model in achieving clinical-grade diagnoses of Spitz nevi, dermal and junctional melanocytic nevi, and melanomas.We created a beginner-level training environment by teaching our algorithm to perform cytologic inferences on 136,216 manually annotated tiles of hematoxylin and eosin-stained slides consisting of unequivocal melanocytic nevi, Spitz nevi, and invasive melanoma cases. We sequentially trained and tested our network to provide a final diagnosis-classification on 39 cases in total. Positive predictive value (precision) and sensitivity (recall) were used to measure our performance.The tile-classification algorithm predicted the 136,216 irrelevant, melanoma, melanocytic nevi, and Spitz nevi tiles at sensitivities of 96%, 93%, 94% and 73%, respectively. The final trained model was able to correctly classify and predict the correct diagnosis in 85.7% of unseen cases (n = 28), reporting at or near screening-level performances for precision and recall of melanoma (76.2%, 100.0%), melanocytic nevi (100.0%, 75.0%), and Spitz nevi (100.0%, 75.0%).Our pilot study proves that convolutional networks trained on cellular morphology to classify melanocytic proliferations can be used as a powerful tool to assist pathologists in screening for melanoma versus other benign lesions.
- Published
- 2022
5. Five Extracurricular Things Commonly Overlooked by Dermatology Residents
- Author
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Jordan V, Wang, Linda T, Doan, Sherry, Yang, Nazanin, Saedi, and Matthew, Keller
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Education, Medical, Graduate ,Surveys and Questionnaires ,Humans ,Internship and Residency ,Curriculum ,Dermatology - Abstract
Dermatology residents have 3 years to master core competencies related to the delivery of patient care, preservation of medical professionalism, and responsible use of health care; however, it is crucial for residents to recognize other things outside of their formal curriculum that are equally vital to their training. Over the years, we have observed residents and now offer our own perspectives. We have collectively observed five extracurricular aspects commonly overlooked by dermatology residents that are important to their education and future practice. (
- Published
- 2022
6. A case of ice‐pack dermatosis in a patient with chronic back pain and review of the literature
- Author
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Sara Sabeti, Suzanne W. Birmingham, Brittany Urso, Michael O. Nguyen, Linda T. Doan, and Nathan W. Rojek
- Subjects
Dermatology - Published
- 2022
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7. Grouped Cerebriform Papules in a Child
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Suzanne W. Birmingham, Linda T. Doan, and Janellen Smith
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Pediatrics, Perinatology and Child Health - Published
- 2022
- Full Text
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8. Primary cytotoxic T-cell lymphomas harbor recurrent targetable alterations in the JAK-STAT pathway
- Author
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Nicholas A. Trum, Joan Guitart, Spencer Ng, Christiane Querfeld, Jaehyuk Choi, Ryanne A. Brown, Paul Haun, Hailing Zhang, Michael S. Khodadoust, Jinming Song, David A. Wada, Lyn M. Duncan, David M. Weinstock, Gary S. Wood, Katie Lee, Alejandro A. Gru, Linda T Doan, Vignesh Shanmugam, Jon C. Aster, Caroline Snowden, Lei Yang, Valentina Nardi, and Mark G. Evans
- Subjects
Primary (chemistry) ,Skin Neoplasms ,business.industry ,Immunology ,JAK-STAT signaling pathway ,Letters to Blood ,Antineoplastic Agents ,Cell Biology ,Hematology ,CD8-Positive T-Lymphocytes ,Lymphoma, T-Cell ,Biochemistry ,Lymphoma, T-Cell, Cutaneous ,STAT Transcription Factors ,hemic and lymphatic diseases ,Mutation ,Cancer research ,Cytotoxic T cell ,Medicine ,Humans ,Molecular Targeted Therapy ,business ,Janus Kinases ,Signal Transduction - Abstract
Primary cytotoxic T cell lymphomas (CTCLs) are a rare subset of aggressive, poor-prognosis T-cell lymphomas targeting the skin; they include primary cutaneous γδT-cell lymphoma, primary cutaneous VD8+ aggressive epidermotropic T cell lymphoma (PCAETCL), and cytotoxic CTCL not otherwise specified. Lee et al report that all 3 subsets have JAK-STAT activation, but PCAETCL uniquely carries JAK2 gene fusions that may render them especially susceptible to JAK inhibitors.
- Published
- 2021
9. Primary cytotoxic T cell lymphomas harbor recurrent targetable alterations in the JAK-STAT pathway
- Author
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Katie Lee, Michael S. Khodadoust, Lyn M. Duncan, Linda T Doan, Vignesh Shanmugam, Gary S. Wood, David M. Weinstock, Nicholas A. Trum, Lei Yang, Mark G. Evans, Ryanne A. Brown, David A. Wada, Joan Guitart, Christine Querfeld, Jaehyuk Choi, Hailing Zhang, Jinming Song, Paul Haun, Valentina Nardi, Caroline Snowden, and Spencer Ng
- Subjects
Cancer Research ,T cell ,Cutaneous T-cell lymphoma ,JAK-STAT signaling pathway ,Cancer ,Biology ,medicine.disease ,Lymphoma ,medicine.anatomical_structure ,Oncology ,hemic and lymphatic diseases ,Cancer research ,medicine ,Cytotoxic T cell ,T-cell lymphoma ,CD8 - Abstract
Background: Primary cytotoxic T cell lymphomas are a heterogenous collection of ill-defined diseases with aggressive disease course and poor response to conventional therapy. Of these, primary cutaneous CD8+ aggressive epidermotropic T cell lymphoma and cutaneous T cell lymphoma, not otherwise specified, have undergone few to no systematic analyses of its genetic landscape. In this study, we classify these lymphomas based on their histological and clinical features and perform systematic genomic analyses to find novel therapeutic targets. Methods: We clinically characterize 35 patients from 10 institutions with cytotoxic T cell lymphoma and performed integrative clinical, pathological, and genetic analyses. We perform Archer™ Heme Fusion on an initial 24 FFPE samples. In addition, we perform DNA and/or RNA sequencing on 11 cases. We functionally validate our genetic findings by transducing alterations into Ba/F3 cells and subsequently performing biochemical assays. In this setting, we assess sensitivity to FDA-approved small molecule inhibitors. We provide orthogonal evidence of transcriptional upregulation by geneset enrichment analysis. Results: We find kinase fusions impacting JAK-STAT signaling in all primary cutaneous CD8+ aggressive epidermotropic T cell lymphomas in our cohort. Three of these fusions have not previously been described in cancer. Known fusions have been shown to upregulate JAK-STAT signaling. Upon each transduction, CAPRIN1-JAK2 and SELENOI-ABL1 cause increased phosphorylation and display IL-3-independent growth compared to control. Upon treatments to small molecule inhibitors, ruxolitinib and imatinib respectively, CAPRIN1-JAK2 and SELENOI-ABL1 expressing cells exhibit sensitivity. Cutaneous T cell lymphoma, not otherwise specified, harbor JAK-STAT hotspot mutations but not kinase fusions. Conclusions: All 9 primary cutaneous CD8+ aggressive epidermotropic T cell lymphomas in our series harbor kinase fusions, while the majority of the cutaneous T cell lymphoma, not otherwise specified, cases in our cohort harbor hotspot JAK/STAT mutations. We provide evidence that the of presence these alterations, which are associated with inhibitor response, depend on cytotoxic T cell lymphoma histology.
- Published
- 2021
- Full Text
- View/download PDF
10. Gait Training in Patients Discharged to a Skilled Nursing Facility Following Total Joint Arthroplasty
- Author
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David J. Wright, Brandon A. Haghverdian, Ran Schwarzkopf, Linda T. Doan, and Dennis Tran
- Subjects
030506 rehabilitation ,medicine.medical_specialty ,Joint arthroplasty ,subacute nursing facility ,medicine.medical_treatment ,lcsh:Geriatrics ,Postacute Care ,rehabilitation ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,lcsh:Orthopedic surgery ,Gait training ,medicine ,Orthopedics and Sports Medicine ,In patient ,physical therapy ,Rehabilitation ,business.industry ,total joint arthroplasty ,Articles ,Cost savings ,ambulation distance ,lcsh:RD701-811 ,lcsh:RC952-954.6 ,Physical therapy ,Surgery ,Geriatrics and Gerontology ,Skilled Nursing Facility ,0305 other medical science ,business ,human activities ,030217 neurology & neurosurgery - Abstract
Background: Expenditures for postacute care in total joint arthroplasty (TJA) have risen dramatically over recent decades. Therefore, efforts are underway to better identify cost savings in postacute rehabilitation centers, such as skilled nursing facilities (SNFs). The primary purpose of this study was to analyze gait training achievements in post-TJA patients in the interval between hospital discharge and the patients’ first 4 days at the SNF. Identification of potential losses in therapeutic progress may lead the way for improved patient care, outcomes, and cost savings. Our hypothesis is that patients discharged to an SNF will have a decline in gait achievements upon transfer from the hospital. Methods: A total of 68 patients who underwent TJA were included. The total distance ambulated during physical therapy (PT) was recorded for the last day of hospital therapy and the first 4 days at the SNF as well as the reported visual analog scale (VAS) pain scores. Results: There was a 73% decline in distance ambulated on SNF day 0 ( Hospital: 138.6 ft vs SNF: 37.9 ft; P < .001) and a 50% decline on SNF day 1 ( Hospital: 103.0 ft; SNF vs 51.1 ft; P < .001) compared to the last hospital session. There were no significant differences in distance walked on SNF days 3 and 4 relative to the last hospital session. The VAS pain scores did not significantly differ on SNF days 0 and 1 compared to the last hospital day but began to significantly decline on SNF day 3 ( Hospital: 4.9; SNF: 3.3; P = .02) and day 4 ( Hospital: 3.9; SNF: 2.3; P = .03). Conclusion: There was a significant decline in ambulatory proficiency in post-TJA patients on the day of and the day following hospital discharge to an SNF. These deficits cannot be attributed to heightened pain levels. Early and progressive ambulation is a recognized component of appropriate PT following TJA. This study therefore highlights the transition from hospital to SNF as a crucial and novel target for improvement in post-TJA care.
- Published
- 2017
11. Bmp indicator mice reveal dynamic regulation of transcriptional response.
- Author
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Anna L Javier, Linda T Doan, Mui Luong, N Soledad Reyes de Mochel, Aixu Sun, Edwin S Monuki, and Ken W Y Cho
- Subjects
Medicine ,Science - Abstract
Cellular responses to Bmp ligands are regulated at multiple levels, both extracellularly and intracellularly. Therefore, the presence of these growth factors is not an accurate indicator of Bmp signaling activity. While a common approach to detect Bmp signaling activity is to determine the presence of phosphorylated forms of Smad1, 5 and 8 by immunostaining, this approach is time consuming and not quantitative. In order to provide a simpler readout system to examine the presence of Bmp signaling in developing animals, we developed BRE-gal mouse embryonic stem cells and a transgenic mouse line that specifically respond to Bmp ligand stimulation. Our reporter identifies specific transcriptional responses that are mediated by Smad1 and Smad4 with the Schnurri transcription factor complex binding to a conserved Bmp-Responsive Element (BRE), originally identified among Drosophila, Xenopus and human Bmp targets. Our BRE-gal mES cells specifically respond to Bmp ligands at concentrations as low as 5 ng/ml; and BRE-gal reporter mice, derived from the BRE-gal mES cells, show dynamic activity in many cellular sites, including extraembryonic structures and mammary glands, thereby making this a useful scientific tool.
- Published
- 2012
- Full Text
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12. A Bmp reporter with ultrasensitive characteristics reveals that high Bmp signaling is not required for cortical hem fate.
- Author
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Linda T Doan, Anna L Javier, Nicole M Furr, Kevin L Nguyen, Ken W Cho, and Edwin S Monuki
- Subjects
Medicine ,Science - Abstract
Insights into Bone morphogenetic protein (Bmp) functions during forebrain development have been limited by a lack of Bmp signaling readouts. Here we used a novel Bmp signaling reporter ("BRE-gal" mice) to study Bmp signaling in the dorsal telencephalon. At early stages, BRE-gal expression was restricted to the dorsal telencephalic midline. At later stages, strong BRE-gal expression occurred in neurons of the marginal zone and dentate gyrus. Comparisons to nuclear phospho-Smad1/5/8 (pSmad) and Msx1 indicated that BRE-gal expression occurred exclusively in neural cells with high-level Bmp signaling. BRE-gal responsiveness to Bmps was confirmed in reporter-negative cortical cells cultured with Bmp4, and both in vivo and in vitro, BRE-gal expression was switch-like, or ultrasensitive. In the early dorsal telencephalon, BRE-gal expression negatively correlated with the cortical selector gene Lhx2, indicating a BRE-gal expression border that coincides with the cortex-hem boundary. However, in Lhx2 null chimeras, neither BRE-gal nor nuclear pSmad increases were observed in ectopic hem cells. These findings establish BRE-gal as an ultrasensitive reporter of Bmp signaling in the dorsal telencephalon, imply that hem fate can be specified at different Bmp signaling intensities, and suggest that Lhx2 primarily regulates the responses to--rather than the intensity of--Bmp signaling in dorsal telencephalic cells.
- Published
- 2012
- Full Text
- View/download PDF
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