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4. Mapping tissue microstructure of brain white matter in vivo in health and disease using diffusion MRI

Author

Liao, Ying, Coelho, Santiago, Chen, Jenny, Ades-Aron, Benjamin, Pang, Michelle, Osorio, Ricardo, Shepherd, Timothy, Lui, Yvonne W., Novikov, Dmitry S., and Fieremans, Els

Subjects
Physics - Medical Physics
Abstract

Diffusion magnetic resonance imaging offers unique in vivo sensitivity to tissue microstructure in brain white matter, which undergoes significant changes during development and is compromised in virtually every neurological disorder. Yet, the challenge is to develop biomarkers that are specific to micrometer-scale cellular features in a human MRI scan of a few minutes. Here we quantify the sensitivity and specificity of a multicompartment diffusion modeling framework to the density, orientation and integrity of axons. We demonstrate that using a machine learning based estimator, our biophysical model captures the morphological changes of axons in early development, acute ischemia and multiple sclerosis (total N=821). The methodology of microstructure mapping is widely applicable in clinical settings and in large imaging consortium data to study development, aging and pathology., Comment: 4 figures, 5 supplementary figures, 1 supplementary table

Published
2023
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5. Optimization and Validation of the DESIGNER dMRI preprocessing pipeline in white matter aging

Author

Chen, Jenny, Ades-Aron, Benjamin, Lee, Hong-Hsi, Mehrin, Subah, Pang, Michelle, Novikov, Dmitry S., Veraart, Jelle, and Fieremans, Els

Subjects
Physics - Medical Physics, Physics - Biological Physics
Abstract

Various diffusion MRI (dMRI) preprocessing pipelines are currently available to yield more accurate diffusion parameters. Here, we evaluated accuracy and robustness of the optimized Diffusion parameter EStImation with Gibbs and NoisE Removal (DESIGNER) pipeline in a large clinical dMRI dataset and using ground truth phantoms. DESIGNER has been modified to improve denoising and target Gibbs ringing for partial Fourier acquisitions. We compared the revisited DESIGNER (Dv2) (including denoising, Gibbs removal, correction for motion, EPI distortion, and eddy currents) against the original DESIGNER (Dv1) pipeline, minimal preprocessing (including correction for motion, EPI distortion, and eddy currents only), and no preprocessing on a large clinical dMRI dataset of 524 control subjects with ages between 25 and 75 years old. We evaluated the effect of specific processing steps on age correlations in white matter with DTI and DKI metrics. We also evaluated the added effect of minimal Gaussian smoothing to deal with noise and to reduce outliers in parameter maps compared to DESIGNER (Dv2)'s noise removal method. Moreover, DESIGNER (Dv2)'s updated noise and Gibbs removal methods were assessed using ground truth dMRI phantom to evaluate accuracy. Results show age correlation in white matter with DTI and DKI metrics were affected by the preprocessing pipeline, causing systematic differences in absolute parameter values and loss or gain of statistical significance. Both in clinical dMRI and ground truth phantoms, DESIGNER (Dv2) pipeline resulted in the smallest number of outlier voxels and improved accuracy in DTI and DKI metrics as noise was reduced and Gibbs removal was improved. Thus, DESIGNER (Dv2) provides more accurate and robust DTI and DKI parameter maps as compared to no preprocessing or minimal preprocessing.

Published
2023
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6. Matching-Adjusted Indirect Comparison of Brexucabtagene Autoleucel (ZUMA-2) and Pirtobrutinib (BRUIN) in Patients with Relapsed/Refractory Mantle Cell Lymphoma Previously Treated with a Covalent Bruton Tyrosine Kinase Inhibitor

Author

Salles, Gilles, Chen, Jenny M. H., Zhang, Ina, Kerbauy, Fabio, Wu, James J., Wade, Sally W., Nunes, Ana, Feng, Chaoling, Kloos, Ioana, Peng, Weimin, Snider, Julia T., Maciel, Dylan, Chan, Keith, Keeping, Sam, and Shah, Bijal

Published
2024
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7. Cellular transformation promotes the incorporation of docosahexaenoic acid into the endolysosome-specific lipid bis(monoacylglycerol)phosphate in breast cancer

Author

Berg, Anastasia L, Showalter, Megan R, Kosaisawe, Nont, Hu, Michelle, Stephens, Nathanial C, Sa, Michael, Heil, Hailey, Castro, Noemi, Chen, Jenny J, VanderVorst, Kacey, Wheeler, Madelyn R, Rabow, Zachary, Cajka, Tomas, Albeck, John, Fiehn, Oliver, and Carraway, Kermit L

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Cancer, Women's Health, 2.1 Biological and endogenous factors, Animals, Mice, Humans, Female, Docosahexaenoic Acids, Breast Neoplasms, Phosphates, Reactive Oxygen Species, Lysophospholipids, Lysosomes, Breast cancer, Bis(monoacylglycerol)phosphate, BMP, Lipidomics, Lysosomal membrane permeabilization, Polyunsaturated fatty acids, Reactive oxygen species, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Bis(monoacylglycero)phosphates (BMPs), a class of lipids highly enriched within endolysosomal organelles, are key components of the lysosomal intraluminal vesicles responsible for activating sphingolipid catabolic enzymes. While BMPs are understudied relative to other phospholipids, recent reports associate BMP dysregulation with a variety of pathological states including neurodegenerative diseases and lysosomal storage disorders. Since the dramatic lysosomal remodeling characteristic of cellular transformation could impact BMP abundance and function, we employed untargeted lipidomics approaches to identify and quantify BMP species in several in vitro and in vivo models of breast cancer and comparative non-transformed cells and tissues. We observed lower BMP levels within transformed cells relative to normal cells, and consistent enrichment of docosahexaenoic acid (22:6) fatty acyl chain-containing BMP species in both human- and mouse-derived mammary tumorigenesis models. Our functional analysis points to a working model whereby 22:6 BMPs serve as reactive oxygen species scavengers in tumor cells, protecting lysosomes from oxidant-induced lysosomal membrane permeabilization. Our findings suggest that breast tumor cells might divert polyunsaturated fatty acids into BMP lipids as part of an adaptive response to protect their lysosomes from elevated reactive oxygen species levels, and raise the possibility that BMP-mediated lysosomal protection is a tumor-specific vulnerability that may be exploited therapeutically.

Published
2023

21. Factors affecting operative autonomy and performance during otolaryngology training: A multicenter trial.

Author

Chen, Jenny, Miller, Lauren, Filimonov, Andrey, Shuman, Elizabeth, Marchiano, Emily, George, Brian, Thorne, Marc, Pletcher, Steven, Platt, Michael, Teng, Marita, Kozin, Elliott, and Gray, Stacey

Subjects
autonomy, competency, performance, residency training, surgical assessments, surgical education
Abstract

OBJECTIVE: Surgical education is changing in an era of new regulations and evolving training cultures. We sought to understand the factors that affect operative experiences during otolaryngology residency. METHODS: From December 2019 to December 2020, five otolaryngology training programs used the SIMPL OR smartphone application to evaluate residents after each operation. Residents and attendings rated the trainees autonomy on a 4-level Zwisch scale, performance on a 5-level scale, and case complexity on a 3-level scale. We examined associations between ratings of autonomy and performance with variables including postgraduate year (PGY), case complexity, gender, week of the academic year (AY), and whether multiple procedures were logged. RESULTS: 78 attendings and 92 residents logged 2984 evaluations. PGY level and week of the AY were positively associated with attending ratings of autonomy and performance (PGY3 vs. PGY2: B = 0.63, p

Published
2022

22. The Cationic Amphiphilic Drug Hexamethylene Amiloride Eradicates Bulk Breast Cancer Cells and Therapy-Resistant Subpopulations with Similar Efficiencies

Author

Berg, Anastasia L, Rowson-Hodel, Ashley, Hu, Michelle, Keeling, Michael, Wu, Hao, VanderVorst, Kacey, Chen, Jenny J, Hatakeyama, Jason, Jilek, Joseph, Dreyer, Courtney A, Wheeler, Madelyn R, Yu, Ai-Ming, Li, Yuanpei, and Carraway, Kermit L

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Stem Cell Research - Nonembryonic - Human, Rare Diseases, Breast Cancer, Women's Health, Stem Cell Research, Stem Cell Research - Nonembryonic - Non-Human, Digestive Diseases, Cancer, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, breast cancer, cancer stem cell, therapy resistance, cationic amphiphilic drug, lysosome-dependent cell death, Oncology and carcinogenesis
Abstract

The resistance of cancer cell subpopulations, including cancer stem cell (CSC) populations, to apoptosis-inducing chemotherapeutic agents is a key barrier to improved outcomes for cancer patients. The cationic amphiphilic drug hexamethylene amiloride (HMA) has been previously demonstrated to efficiently kill bulk breast cancer cells independent of tumor subtype or species but acts poorly toward non-transformed cells derived from multiple tissues. Here, we demonstrate that HMA is similarly cytotoxic toward breast CSC-related subpopulations that are resistant to conventional chemotherapeutic agents, but poorly cytotoxic toward normal mammary stem cells. HMA inhibits the sphere-forming capacity of FACS-sorted human and mouse mammary CSC-related cells in vitro, specifically kills tumor but not normal mammary organoids ex vivo, and inhibits metastatic outgrowth in vivo, consistent with CSC suppression. Moreover, HMA inhibits viability and sphere formation by lung, colon, pancreatic, brain, liver, prostate, and bladder tumor cell lines, suggesting that its effects may be applicable to multiple malignancies. Our observations expose a key vulnerability intrinsic to cancer stem cells and point to novel strategies for the exploitation of cationic amphiphilic drugs in cancer treatment.

Published
2022

28. Augmented Galatea for Physical Pygmalion: A Phenomenological Approach to Intimacy in VTubers in the East Asia Region

Author

Liberati, Nicola, Chen, Jenny Jiaying, Edmonds, Ernest, Founding Editor, Vear, Craig, Series Editor, Brown, Paul, Editorial Board Member, Bryan-Kinns, Nick, Editorial Board Member, England, David, Editorial Board Member, Ferguson, Sam, Editorial Board Member, Ferran, Bronaċ, Editorial Board Member, Hugill, Andrew, Editorial Board Member, Lambert, Nicholas, Editorial Board Member, Lowgren, Jonas, Editorial Board Member, Yi-Luen Do, Ellen, Editorial Board Member, Clark, Sean, Editorial Board Member, Zagalo, Nelson, Editorial Board Member, Rauterberg, Matthias, Editorial Board Member, and Geroimenko, Vladimir, editor

Published
2023
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31. An Observational Study of the Effect of Nike Vaporfly Shoes on Marathon Performance

Author

Guinness, Joseph, Bhattacharya, Debasmita, Chen, Jenny, Chen, Max, and Loh, Angela

Subjects
Statistics - Applications
Abstract

We collected marathon performance data from a systematic sample of elite and sub-elite athletes over the period 2015 to 2019, then searched the internet for publicly-available photographs of these performances, identifying whether the Nike Vaporfly shoes were worn or not in each performance. Controlling for athlete ability and race difficulty, we estimated the effect on marathon times of wearing the Vaporfly shoes. Assuming that the effect of Vaporfly shoes is additive, we estimate that the Vaporfly shoes improve men's times between 2.0 and 3.9 minutes, while they improve women's times between 0.8 and 3.5 minutes. Assuming that the effect of Vaporfly shoes is multiplicative, we estimate that they improve men's times between 1.4 and 2.8 percent and women's performances between 0.6 and 2.2 percent. The improvements are in comparison to the shoe the athlete was wearing before switching to Vaporfly shoes, and represents an expected improvement rather than a guaranteed improvement.

Published
2020

32. “It Depends”: How Children Reason about Stable and Unstable Causes

Author

Vasilyeva, Nadya, Murphy, Mei, Bohra, Oce, Chen, Jenny, Cuevas, Selena Xandra, Katteri, Samhita, Lombrozo, Tania, and Gopnik, Alison

Subjects
cognitive science
Abstract

Adults have been shown to favor stable causal relationships – those that hold robustly across background contexts – in their actions and causal/explanatory generalizations (Vasilyeva et al, 2018). Here we explore how this preference develops. We present results from one study with 141 4-7-year-olds investigating whether children pay attention to causal stability when they explain observations and design interventions in novel contexts. We report developmental shifts in reliance on causal stability in a range of inferential tasks, highlight the important role of perceived average causal strength in determining children’s causal preferences, and discuss the implications of our findings for theories of early causal learning. To our knowledge, this is the first study exploring the role of stability in children’s causal reasoning.

Published
2021

34. Gonioscopy-assisted Transluminal Trabeculotomy (GATT) in Patients With Secondary Open-Angle Glaucoma Following Vitreoretinal Surgery

Author

Quan, Ann V, Yannuzzi, Nicolas A, Chen, Jenny, Wang, Ye Elaine, Townsend, Justin H, and Chang, Ta Chen

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Eye Disease and Disorders of Vision, Neurodegenerative, Neurosciences, Aging, 6.1 Pharmaceuticals, 6.4 Surgery, Evaluation of treatments and therapeutic interventions, Eye, Adolescent, Adult, Aged, Female, Follow-Up Studies, Glaucoma, Open-Angle, Gonioscopy, Humans, Intraocular Pressure, Male, Middle Aged, Plastic Surgery Procedures, Research Design, Retrospective Studies, Tonometry, Ocular, Trabeculectomy, Treatment Outcome, Vitreoretinal Surgery, Young Adult, gonioscopy-assisted transluminal trabeculotomy, secondary open-angle glaucoma, vitreoretinal surgery, silicone oil, angle surgery, Clinical Sciences, Ophthalmology & Optometry, Ophthalmology and optometry
Abstract

PurposeTo examine the short-term efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in a series of patients who developed glaucoma following vitreoretinal surgery.Patients and methodsRetrospective case series of consecutive patients aged above 18 years with secondary open-angle glaucoma following vitreoretinal surgery who had undergone GATT between January 2015 and June 2019. Eyes were excluded if there is

Published
2020

47. Nonlinear Mixed-Effects Modeling

Author

Chen, Ding-Geng (Din), Chen, Jenny K., Chen, Ding-Geng (Din), Series Editor, Bekker, Andriëtte, Editorial Board Member, Coelho, Carlos A., Editorial Board Member, Finkelstein, Maxim, Editorial Board Member, Wilson, Jeffrey R., Editorial Board Member, and Chen, Jenny K.

Published
2021
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48. The Generalized Linear Model

Author

Chen, Ding-Geng (Din), Chen, Jenny K., Chen, Ding-Geng (Din), Series Editor, Bekker, Andriëtte, Editorial Board Member, Coelho, Carlos A., Editorial Board Member, Finkelstein, Maxim, Editorial Board Member, Wilson, Jeffrey R., Editorial Board Member, and Chen, Jenny K.

Published
2021
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49. Nonlinear Regression Modeling

Author

Chen, Ding-Geng (Din), Chen, Jenny K., Chen, Ding-Geng (Din), Series Editor, Bekker, Andriëtte, Editorial Board Member, Coelho, Carlos A., Editorial Board Member, Finkelstein, Maxim, Editorial Board Member, Wilson, Jeffrey R., Editorial Board Member, and Chen, Jenny K.

Published
2021
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50. Generalized Multi-Level Model for Dichotomous Outcome

Author

Chen, Ding-Geng (Din), Chen, Jenny K., Chen, Ding-Geng (Din), Series Editor, Bekker, Andriëtte, Editorial Board Member, Coelho, Carlos A., Editorial Board Member, Finkelstein, Maxim, Editorial Board Member, Wilson, Jeffrey R., Editorial Board Member, and Chen, Jenny K.

Published
2021
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