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A, B, C'S Of Trk Receptors And Their Ligands In Ocular Repair, Akash Gupta, Jeremias G Galletti, Zhiyuan Yu, Kevin Burgess, Cintia S de Paiva 2022 The Texas Medical Center Library

A, B, C'S Of Trk Receptors And Their Ligands In Ocular Repair, Akash Gupta, Jeremias G Galletti, Zhiyuan Yu, Kevin Burgess, Cintia S De Paiva

Faculty, Staff and Students Publications

Neurotrophins are a family of closely related secreted proteins that promote differentiation, development, and survival of neurons, which include nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4. All neurotrophins signal through tropomyosin receptor kinases (TrkA, TrkB, and TrkC) which are more selective to NGF, brain-derived neurotrophic factor, and neurotrophin-3, respectively. NGF is the most studied neurotrophin in the ocular surface and a human recombinant NGF has reached clinics, having been approved to treat neurotrophic keratitis. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 are less studied neurotrophins in the ocular surface, even though brain-derived neurotrophic factor is well characterized in …


Corneal Edema Associated With Degenerating Soemmering Ring Cataract: Clinical-Pathologic Correlation, Jordan P Safran, Nathan Nataneli, Jayesh Vazirani, Ralph C. Eagle Jr, Tatyana Milman 2022 Thomas Jefferson University

Corneal Edema Associated With Degenerating Soemmering Ring Cataract: Clinical-Pathologic Correlation, Jordan P Safran, Nathan Nataneli, Jayesh Vazirani, Ralph C. Eagle Jr, Tatyana Milman

Wills Eye Hospital Papers

Purpose: To report three patients with an uncommon delayed complication of cataract extraction: corneal edema following dispersion of calcific lens particles from a degenerating Soemmering ring cataract.

Observations: We report three patients, 75-92 years old, presenting with corneal edema and dispersed, degenerated calcific lens material in the anterior chamber and vitreous 20-30 years after cataract surgery. In all patients, calcific particles studded the posterior surface of the cornea in a gravity-dependent distribution without apparent inflammation and were associated with localized corneal edema. In one patient, calcific particles were also associated with secondary open angle glaucoma. Deposits originated from the calcified …


Frosted Branch Angiitis Presenting After A Sars-Cov-2 Infection., Akhila Alapati, Nathaniel Cameron, Sean Gratton, Erin Stahl, Mary Champion 2022 Children's Mercy Kansas City

Frosted Branch Angiitis Presenting After A Sars-Cov-2 Infection., Akhila Alapati, Nathaniel Cameron, Sean Gratton, Erin Stahl, Mary Champion

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: To report a case of frosted branch angiitis presenting in a pediatric patient with unremarkable laboratory work-up apart from SARS-CoV-2 IgG antibodies.

OBSERVATIONS: Less than four weeks after a SARS-CoV-2 infection, a 10 year-old female presented to the emergency department with severe headache and intermittent fevers. During her hospital admission, the ophthalmology service was consulted for blurry vision. Subsequent eye examination revealed frosted branch angiitis. The patient initially received intravenous corticosteroids but was escalated to plasmapheresis to achieve resolution of her symptoms. Outpatient maintenance therapy consisted of an oral Prednisone taper and Infliximab infusion.

CONCLUSION AND IMPORTANCE: This case …


Pi3k Isoform-Specific Regulation Of Leader And Follower Cell Function For Collective Migration And Proliferation In Response To Injury, Morgan D Basta, A. Menko, Janice L Walker 2022 Thomas Jefferson University

Pi3k Isoform-Specific Regulation Of Leader And Follower Cell Function For Collective Migration And Proliferation In Response To Injury, Morgan D Basta, A. Menko, Janice L Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

To ensure proper wound healing it is important to elucidate the signaling cues that coordinate leader and follower cell behavior to promote collective migration and proliferation for wound healing in response to injury. Using an ex vivo post-cataract surgery wound healing model we investigated the role of class I phosphatidylinositol-3-kinase (PI3K) isoforms in this process. Our findings revealed a specific role for p110α signaling independent of Akt for promoting the collective migration and proliferation of the epithelium for wound closure. In addition, we found an important role for p110α signaling in orchestrating proper polarized cytoskeletal organization within both leader and …


Safety Of Simultaneous Bilateral Intravitreal Versus Unilateral Anti-Vasculo-Endothelial Growth Factors Injection In An Operating Room Setting, Irfan Kabiruddin Jeeva, Sidra Masud, Rehman Siddiqui, Hadees Murad Fahad 2022 Aga Khan University Hospital

Safety Of Simultaneous Bilateral Intravitreal Versus Unilateral Anti-Vasculo-Endothelial Growth Factors Injection In An Operating Room Setting, Irfan Kabiruddin Jeeva, Sidra Masud, Rehman Siddiqui, Hadees Murad Fahad

Department of Ophthalmology & Visual Sciences

Objectives: Chorioretinal diseases requiring the use of anti-vascular endothelial growth (anti-VEGF) injections often occur in both eyes simultaneously. This can necessitate injecting both eyes together rather than one eye at a time. The purpose of the study was to determine whether simultaneous bilateral intravitreal injections of anti-VEGF agents are safe when administered in an operation theatre setting.
Methods: Retrospective review of data was conducted. Single center study conducted in a tertiary care hospital in Karachi Pakistan. Approximately 30,000 eyes that received anti-VEGF injection during a 10-year study period were included (March 2008-February 2018). Patients who were lost to follow up …


Combination Of Aibp, Apoa-I, And Aflibercept Overcomes Anti-Vegf Resistance In Neovascular Amd By Inhibiting Arteriolar Choroidal Neovascularization, Zhao Zhang, Megan M Shen, Yingbin Fu 2022 The Texas Medical Center Library

Combination Of Aibp, Apoa-I, And Aflibercept Overcomes Anti-Vegf Resistance In Neovascular Amd By Inhibiting Arteriolar Choroidal Neovascularization, Zhao Zhang, Megan M Shen, Yingbin Fu

Faculty, Staff and Students Publications

PURPOSE: Anti-VEGF resistance represents a major unmet clinical need in the management of choroidal neovascularization (CNV). We have previously reported that a combination of AIBP, apoA-I, and an anti-VEGF antibody overcomes anti-VEGF resistance in laser-induced CNV in old mice in prevention experiments. The purpose of this work is to conduct a more clinically relevant study to assess the efficacy of the combination of AIBP, apoA-I, and aflibercept in the treatment of anti-VEGF resistance of experimental CNV at different time points after laser photocoagulation.

METHODS: To understand the pathobiology of anti-VEGF resistance, we performed comprehensive examinations of the vascular morphology of …


A Reactivation Of Ocular Toxoplasmosis During Pregnancy, Brett Garee OD, MS, Sarah Dieter OD, Pete Liette OD 2022 Department of Veterans Affairs

A Reactivation Of Ocular Toxoplasmosis During Pregnancy, Brett Garee Od, Ms, Sarah Dieter Od, Pete Liette Od

Optometric Clinical Practice

Background: Toxoplasma gondii is a parasite estimated to affect over 500 million people worldwide. The feline is the definitive host for the parasite and infection may be acquired or congenital via maternal transmission. Humans may acquire the infection by ingestion of raw or undercooked meats and vegetables, contaminated water, or exposure to infected cat feces. The infection is often benign, self-limiting, and asymptomatic for humans, but potentially life threatening to infants or the immunocompromised patient.

Case Report: A 22 year-old Caucasian female, pregnant at 12 weeks gestation, presented to the optometry service with acute symptoms of hazy vision …


Advances In Retinopathy Of Prematurity Imaging, Taku Wakabayashi, Samir N. Patel, J. P. Campbell, Emmanuel Y. Chang, Eric D. Nudleman, Yoshihiro Yonekawa 2022 Thomas Jefferson University

Advances In Retinopathy Of Prematurity Imaging, Taku Wakabayashi, Samir N. Patel, J. P. Campbell, Emmanuel Y. Chang, Eric D. Nudleman, Yoshihiro Yonekawa

Wills Eye Hospital Papers

Retinopathy of prematurity (ROP) remains the leading cause of childhood blindness worldwide. Recent advances in ROP imaging have significantly improved our understanding of the pathogenesis and pathophysiological course of ROP including the acute phase, regression, reactivation, and late complications, known as adult ROP. Recent progress includes various contact and noncontact wide-field imaging devices for fundus imaging, smartphone-based fundus photography, wide-field fluorescein angiography, handheld optical coherence tomography (OCT) devices for wide-field en face OCT images, and OCT angiography. Images taken by those devices were incorporated in the recently updated guidelines of ROP, the International Classification of Retinopathy of Prematurity, Third Edition …


Night Vision Restored In Days After Decades Of Congenital Blindness, Samuel G Jacobson, Artur V Cideciyan, Allen Ho, Alejandro J Roman, Vivian Wu, Alexandra V Garafalo, Alexander Sumaroka, Arun K Krishnan, Malgorzata Swider, Abraham A Mascio, Christine N Kay, Dan Yoon, Kenji P Fujita, Sanford L Boye, Igor V Peshenko, Alexander M Dizhoor, Shannon E Boye 2022 University of Pennsylvania

Night Vision Restored In Days After Decades Of Congenital Blindness, Samuel G Jacobson, Artur V Cideciyan, Allen Ho, Alejandro J Roman, Vivian Wu, Alexandra V Garafalo, Alexander Sumaroka, Arun K Krishnan, Malgorzata Swider, Abraham A Mascio, Christine N Kay, Dan Yoon, Kenji P Fujita, Sanford L Boye, Igor V Peshenko, Alexander M Dizhoor, Shannon E Boye

Wills Eye Hospital Papers

Signaling of vision to the brain starts with the retinal phototransduction cascade which converts visible light from the environment into chemical changes. Vision impairment results when mutations inactivate proteins of the phototransduction cascade. A severe monogenically inherited blindness, Leber congenital amaurosis (LCA), is caused by mutations in the GUCY2D gene, leading to a molecular defect in the production of cyclic GMP, the second messenger of phototransduction. We studied two patients with GUCY2D-LCA who were undergoing gene augmentation therapy. Both patients had large deficits in rod photoreceptor-based night vision before intervention. Within days of therapy, rod vision in both …


Suspicious Retinal Lesion With A Distinctive Appearance, G Brandon Caudill, Mrittika Sen, Carol L. Shields 2022 Thomas Jefferson University

Suspicious Retinal Lesion With A Distinctive Appearance, G Brandon Caudill, Mrittika Sen, Carol L. Shields

Wills Eye Hospital Papers

No abstract provided.


Imbalanced Il-37/Tnf-Α/Ctss Signaling Disrupts Corneal Epithelial Barrier In A Dry Eye Model In Vitro, Yun Zhang, Jin-Miao Li, Rong Lu, Zhao Liu, Xin Chen, Cintia S de Paiva, Stephen C Pflugfelder, De-Quan Li 2022 The Texas Medical Center Library

Imbalanced Il-37/Tnf-Α/Ctss Signaling Disrupts Corneal Epithelial Barrier In A Dry Eye Model In Vitro, Yun Zhang, Jin-Miao Li, Rong Lu, Zhao Liu, Xin Chen, Cintia S De Paiva, Stephen C Pflugfelder, De-Quan Li

Faculty, Staff and Students Publications

PURPOSE: To explore novel role and molecular mechanism of a natural anti-inflammatory cytokine interleukin (IL) 37 in preventing corneal epithelial barrier disruption from hyperosmolar stress as can occur in dry eye disease.

METHODS: Primary human corneal epithelial cells (HCECs) were cultured from fresh donor limbal explants. An in vitro dry eye model with hyperosmolar stress was established by switching HCECs from isosmolar (312mOsM) to hyperosmolar medium (350-500 mOsM), and some cells were treated with rhIL-37 or rhTNF-α, for different periods (2-48 h). The expression of cytokines and cathepsin S, and barrier protein integrity were evaluated by RT-qPCR, ELISA, and immunofluorescent …


Age Differential Response To Bevacizumab Therapy In Choroidal Neovascularization In Rabbits, Van Phuc Nguyen, Jessica Henry, Josh Zhe, Quynh Kieu, Wei Qian, Yingbin Fu, Xueding Wang, Yannis M Paulus 2022 The Texas Medical Center Library

Age Differential Response To Bevacizumab Therapy In Choroidal Neovascularization In Rabbits, Van Phuc Nguyen, Jessica Henry, Josh Zhe, Quynh Kieu, Wei Qian, Yingbin Fu, Xueding Wang, Yannis M Paulus

Faculty, Staff and Students Publications

Choroidal neovascularization (CNV) in young rabbits has been shown to have a rapid, robust response after treatment with bevacizumab, an anti-vascular endothelial growth factor (VEGF) medication. This investigation evaluates an age differential response to bevacizumab in older populations of rabbits using multimodal high resolution molecular imaging. Young (4 months old) and life span (14 months old) rabbits were given subretinal injections of Matrigel and VEGF to produce CNV. All CNV rabbit models were then treated with a bevacizumab intravitreal injection. Rabbits were then monitored longitudinally using photoacoustic microscopy (PAM), optical coherence tomography (OCT), color photography, and fluorescence imaging. Chain-like gold …


Global Current Practice Patterns For The Management Of Hyphema, Sarah C Miller, Prajna Meeralakshmi, Michael J Fliotsos, Grant A Justin, Yoshihiro Yonekawa, Ariel Chen, Annette K Hoskin, Richard J Blanch, Kara M Cavuoto, Rebecca Low, Ximin Li, Matthew Gardiner, T Y Alvin Liu, Ankoor S Shah, James D Auran, Rupesh Agrawal, Fasika A Woreta, International Globe and Adnexal Trauma Epidemiology Study (IGATES) 2022 Johns Hopkins University School of Medicine

Global Current Practice Patterns For The Management Of Hyphema, Sarah C Miller, Prajna Meeralakshmi, Michael J Fliotsos, Grant A Justin, Yoshihiro Yonekawa, Ariel Chen, Annette K Hoskin, Richard J Blanch, Kara M Cavuoto, Rebecca Low, Ximin Li, Matthew Gardiner, T Y Alvin Liu, Ankoor S Shah, James D Auran, Rupesh Agrawal, Fasika A Woreta, International Globe And Adnexal Trauma Epidemiology Study (Igates)

Wills Eye Hospital Papers

Purpose: Hyphema is a sequela of ocular trauma and can be associated with significant morbidity. Management of this condition is variable and can depend on individual institutional guidelines. We aimed to summarize current practices in hyphema management across ophthalmological institutions worldwide.

Methods: A cross-sectional online survey was conducted across North America, Asia, South America, Africa, Europe, and Australia from August 2020 to January 2021. The survey assessed the existing practices in the management of hyphema at each institution.

Results: For layered hyphema, topical steroids were routinely administered by 34 (of 36 respondents, 94.4%) institutions, of which prednisolone was the preferred …


Intrinsic Disorder In Bap1 And Its Association With Uveal Melanoma., Mak B Djulbegovic, David J Taylor, Vladimir N Uversky, Anat Galor, Carol L Shields, Carol L Karp 2022 University of Miami

Intrinsic Disorder In Bap1 And Its Association With Uveal Melanoma., Mak B Djulbegovic, David J Taylor, Vladimir N Uversky, Anat Galor, Carol L Shields, Carol L Karp

Wills Eye Hospital Papers

BACKGROUND: Specific subvariants of uveal melanoma (UM) are associated with increased rates of metastasis compared to other subvariants. BRCA1 (BReast CAncer gene 1)-associated protein-1 (BAP1) is encoded by a gene that has been linked to aggressive behavior in UM.

METHODS: We evaluated BAP1 for the presence of intrinsically disordered protein regions (IDPRs) and its protein-protein interactions (PPI). We evaluated specific sequence-based features of the BAP1 protein using a set of bioinformatic databases, predictors, and algorithms.

RESULTS: We show that BAP1's structure contains extensive IDPRs as it is highly enriched in proline residues (the most disordered amino acid; p-value < 0.05), the average percent of predicted disordered residues (PPDR) was 57.34%, and contains 9 disorder-based binding sites (ie. molecular recognition features (MoRFs)). BAP1's intrinsic disorder allows it to engage in a complex PPI network with at least 49 partners (p …


Coats Plus Syndrome With New Observation Of Drusenoid Retinal Pigment Epithelial Detachments In A Teenager, Kushal U. Agrawal, Nicholas E. Kalafatis, Carol L. Shields 2022 Thomas Jefferson University

Coats Plus Syndrome With New Observation Of Drusenoid Retinal Pigment Epithelial Detachments In A Teenager, Kushal U. Agrawal, Nicholas E. Kalafatis, Carol L. Shields

Wills Eye Hospital Papers

Purpose: To describe a case of Coats Plus Syndrome (CPS), a vision and life threatening disease belonging to a family of diseases known as the Telomere Biology Disorders.

Observations: A 15-year-old girl with a history of small for gestational age, short stature, microcephaly, thinning/ greying of scalp hair, skin hyperpigmentation, nail ridging, and multiple pathological fractures presented with bilateral Coats-like retinopathy. We discovered a new observation of multiple peripheral pinpoint retinal pigment epithelial detachments (PEDs). Further genetic testing revealed CTC1 gene mutation and she was diagnosed with Coats plus syndrome with features of dyskeratosis congenita, a telomere biology disorder.

Conclusion …


Computer-Vision-Based Vibration Tracking Using A Digital Camera: A Sparse-Optical-Flow-Based Target Tracking Method, Guang-Yu Nie, Saran Srikanth Bodda, Harleen Kaur Sandhu, Kevin Han, Abhinav Gupta 2022 The Texas Medical Center Library

Computer-Vision-Based Vibration Tracking Using A Digital Camera: A Sparse-Optical-Flow-Based Target Tracking Method, Guang-Yu Nie, Saran Srikanth Bodda, Harleen Kaur Sandhu, Kevin Han, Abhinav Gupta

Faculty, Staff and Student Publications

Computer-vision-based target tracking is a technology applied to a wide range of research areas, including structural vibration monitoring. However, current target tracking methods suffer from noise in digital image processing. In this paper, a new target tracking method based on the sparse optical flow technique is introduced for improving the accuracy in tracking the target, especially when the target has a large displacement. The proposed method utilizes the Oriented FAST and Rotated BRIEF (ORB) technique which is based on FAST (Features from Accelerated Segment Test), a feature detector, and BRIEF (Binary Robust Independent Elementary Features), a binary descriptor. ORB maintains …


Mutations In Bcor, A Co-Repressor Of Crx/Otx2, Are Associated With Early-Onset Retinal Degeneration, Maéva Langouët, Christine Jolicoeur, Awais Javed, Pierre Mattar, Micah D Gearhart, Stephen P Daiger, Mette Bertelsen, Lisbeth Tranebjærg, Nanna D Rendtorff, Karen Grønskov, Catherine Jespersgaard, Rui Chen, Zixi Sun, Hui Li, Najmeh Alirezaie, Jacek Majewski, Vivian J Bardwell, Ruifang Sui, Robert K Koenekoop, Michel Cayouette 2022 The Texas Medical Center Library

Mutations In Bcor, A Co-Repressor Of Crx/Otx2, Are Associated With Early-Onset Retinal Degeneration, Maéva Langouët, Christine Jolicoeur, Awais Javed, Pierre Mattar, Micah D Gearhart, Stephen P Daiger, Mette Bertelsen, Lisbeth Tranebjærg, Nanna D Rendtorff, Karen Grønskov, Catherine Jespersgaard, Rui Chen, Zixi Sun, Hui Li, Najmeh Alirezaie, Jacek Majewski, Vivian J Bardwell, Ruifang Sui, Robert K Koenekoop, Michel Cayouette

Faculty, Staff and Student Publications

Many transcription factors regulating the production, survival, and function of photoreceptor cells have been identified, but little is known about transcriptional co-regulators in retinal health and disease. Here, we show that BCL6 co-repressor (BCOR), a Polycomb repressive complex 1 factor mutated in various cancers, is involved in photoreceptor degenerative diseases. Using proteomics and transcription assays, we report that BCOR interacts with the transcription factors CRX and OTX2 and reduces their ability to activate the promoters of photoreceptor-specific genes. CUT&RUN sequencing further shows that BCOR shares genome-wide binding profiles with CRX/OTX2, consistent with a general co-repression activity. We also identify missense …


Sars-Cov-2 Invasion And Pathological Links To Prion Disease, Walter J. Lukiw, Vivian R. Jaber, Aileen I. Pogue, Yuhai Zhao 2022 LSU Health Sciences Center - New Orleans

Sars-Cov-2 Invasion And Pathological Links To Prion Disease, Walter J. Lukiw, Vivian R. Jaber, Aileen I. Pogue, Yuhai Zhao

School of Medicine Faculty Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 disease, is a highly infectious and transmissible viral pathogen that continues to impact human health globally. Nearly ~600 million people have been infected with SARS-CoV-2, and about half exhibit some degree of continuing health complication, generically referred to as long COVID. Lingering and often serious neurological problems for patients in the post-COVID-19 recovery period include brain fog, behavioral changes, confusion, delirium, deficits in intellect, cognition and memory issues, loss of balance and coordination, problems with vision, visual processing and hallucinations, encephalopathy, encephalitis, neurovascular or cerebrovascular insufficiency, and/or …


Tnf-Α And Nf-Κb Signaling Play A Critical Role In Cigarette Smoke-Induced Epithelial-Mesenchymal Transition Of Retinal Pigment Epithelial Cells In Proliferative Vitreoretinopathy, Victor Wang, Alison Heffer, Elisa Roztocil, Steven E Feldon, Richard T Libby, Collynn F Woeller, Ajay E Kuriyan 2022 University of Rochester Medical Center

Tnf-Α And Nf-Κb Signaling Play A Critical Role In Cigarette Smoke-Induced Epithelial-Mesenchymal Transition Of Retinal Pigment Epithelial Cells In Proliferative Vitreoretinopathy, Victor Wang, Alison Heffer, Elisa Roztocil, Steven E Feldon, Richard T Libby, Collynn F Woeller, Ajay E Kuriyan

Wills Eye Hospital Papers

Proliferative vitreoretinopathy (PVR) is characterized by the growth and contraction of cellular membranes within the vitreous cavity and on both surfaces of the retina, resulting in recurrent retinal detachments and poor visual outcomes. Proinflammatory cytokines like tumor necrosis factor alpha (TNFα) have been associated with PVR and the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. Cigarette smoke is the only known modifiable risk factor for PVR, but the mechanisms are unclear. The purpose of this study was to examine the impact of cigarette smoke on the proinflammatory TNFα/NF-κB/Snail pathway in RPE cells to better understand the mechanisms through …


Cyberknife Robotic-Assisted Stereotactic Radiosurgery For Advanced Stages Of Ciliochoroidal Uveal Melanoma. Preliminary Results In Mexico, Gustavo Ortiz-Morales, Irving Dominguez-Varela, Daniela E. Gomez-Elizondo, Erik Perez-Ramos, Sara González-Godínez, Dione Aguilar y Méndez, Christian Estrada-Hernández, Ramiro Corral, Octavio Zamorano-Gómez, Carol L. Shields, Lauren A. Dalvin, Efren Gonzalez-Monroy, David Ancona-Lezama 2022 Hospital Alta Especialidad

Cyberknife Robotic-Assisted Stereotactic Radiosurgery For Advanced Stages Of Ciliochoroidal Uveal Melanoma. Preliminary Results In Mexico, Gustavo Ortiz-Morales, Irving Dominguez-Varela, Daniela E. Gomez-Elizondo, Erik Perez-Ramos, Sara González-Godínez, Dione Aguilar Y Méndez, Christian Estrada-Hernández, Ramiro Corral, Octavio Zamorano-Gómez, Carol L. Shields, Lauren A. Dalvin, Efren Gonzalez-Monroy, David Ancona-Lezama

Wills Eye Hospital Papers

Objective: The objective of this study was to report the early results of CyberKnife® (CK®) stereotactic radiosurgery in advanced stages of ciliochoroidal (CBCh) melanoma in Mexican patients.

Methods: A retrospective review of charts was performed to analyze the outcomes of patients who underwent CK® (Accuray Inc, Sunnyvale, CA, United States).

Results: Four patients with CBCh melanoma were treated under this protocol. The mean age was 53.2 ± 5.3 years (range, 47-60). Median of follow-up was 9.5 ± 3.1 months (range, 5-12). Mean tumor diameter was 13.49 mm, mean thickness, 11.74 mm, and mean gross tumor volume …


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