Digital Commons Network^™

Using Patient-Specific 3d Modeling And Simulations To Optimize Microwave Ablation Therapy For Liver Cancer, Amirreza Heshmat, Caleb S O'Connor, Jessica Albuquerque Marques Silva, Iwan Paolucci, Aaron Kyle Jones, Bruno C Odisio, Kristy K Brock

Faculty, Staff and Student Publications

Microwave ablation (MWA) of liver tumors presents challenges like under- and over-ablation, potentially leading to inadequate tumor destruction and damage to healthy tissue. This study aims to develop personalized three-dimensional (3D) models to simulate MWA for liver tumors, incorporating patient-specific characteristics. The primary objective is to validate the predicted ablation zones compared to clinical outcomes, offering insights into MWA before therapy to facilitate accurate treatment planning. Contrast-enhanced CT images from three patients were used to create 3D models. The simulations used coupled electromagnetic wave propagation and bioheat transfer to estimate the temperature distribution, predicting tumor destruction and ablation margins. The …

A Qualitative Exploration Of Well-Being In Cancer Survivorship: Implications For Counselors, Hallie M. Sylvestro, Lindsey K. Umstead, Heather Delgado, Christopher Lawrence, Keith Mobley, Kelly L. Wester, Andrew Wood

Adultspan Journal

Adult cancer survivors represent an important–and growing–population that could benefit from counseling services. This study employed consensual qualitative research to examine the well-being experiences of eight cancer survivors. Findings suggest a broad range of changes to individual well-being following cancer diagnosis and treatment, and indicate counseling can provide an ideal setting for processing such changes. Recommendations for counseling practice and future research are provided.

The Effect Of A Dynamic Lighting Schedule On Neurobehavioral Performance During A 45-Day Simulated Space Mission, Leilah Grant, Brianne Kent, Shadab Rahman, Melissa St Hilaire, Crystal Kirkley, Kevin Gregory, Toni Clark, John Hanifin, Laura Barger, Charles Czeisler, George Brainard, Steven Lockley, Erin Flynn-Evans

Department of Neurology Faculty Papers

Study Objective: We previously reported that during a 45-day simulated space mission, a dynamic lighting schedule (DLS) improved circadian phase alignment and performance assessed once on selected days. This study aimed to evaluate how DLS affected performance on a 5-minute psychomotor vigilance task (PVT) administered multiple times per day on selected days.

Methods: Sixteen crewmembers (37.4 ± 6.7 years; 5F) underwent six cycles of 2 × 8-hour/night followed by 5 × 5-hour/night sleep opportunities. During the DLS (n = 8), daytime white light exposure was blue-enriched (∼6000 K; Level 1: 1079, Level 2: 76 melanopic equivalent daytime illuminance (melEDI) lux) …

Molecular Classification And Biomarkers Of Outcome With Immunotherapy In Extensive-Stage Small-Cell Lung Cancer: Analyses Of The Caspian Phase 3 Study, Mingchao Xie, Miljenka Vuko, Jaime Rodriguez-Canales, Johannes Zimmermann, Markus Schick, Cathy O'Brien, Luis Paz-Ares, Jonathan W Goldman, Marina Chiara Garassino, Carl M Gay, John V Heymach, Haiyi Jiang, J Carl Barrett, Ross A Stewart, Zhongwu Lai, Lauren A Byers, Charles M Rudin, Yashaswi Shrestha

Faculty, Staff and Student Publications

BACKGROUND: We explored potential predictive biomarkers of immunotherapy response in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with durvalumab (D) + tremelimumab (T) + etoposide-platinum (EP), D + EP, or EP in the randomized phase 3 CASPIAN trial.

METHODS: 805 treatment-naïve patients with ES-SCLC were randomized (1:1:1) to receive D + T + EP, D + EP, or EP. The primary endpoint was overall survival (OS). Patients were required to provide an archived tumor tissue block (or ≥ 15 newly cut unstained slides) at screening, if these samples existed. After assessment for programmed cell death ligand-1 expression and tissue …

Metabolic Alterations And Cellular Responses To Β-Hydroxybutyrate Treatment In Breast Cancer Cells, Hadas Fulman-Levy, Raichel Cohen-Harazi, Bar Levi, Lital Argaev-Frenkel, Ifat Abramovich, Eyal Gottlieb, Sarah Hofmann, Igor Koman, Elimelech Nesher

Faculty, Staff and Student Publications

BACKGROUND: The ketogenic diet (KD), based on high fat (over 70% of daily calories), low carbohydrate, and adequate protein intake, has become popular due to its potential therapeutic benefits for several diseases including cancer. Under KD and starvation conditions, the lack of carbohydrates promotes the production of ketone bodies (KB) from fats by the liver as an alternative source of metabolic energy. KD and starvation may affect the metabolism in cancer cells, as well as tumor characteristics. The aim of this study is to evaluate the effect of KD conditions on a wide variety of aspects of breast cancer cells …

Noncontrast Ct Selected Thrombectomy Vs Medical Management For Late-Window Anterior Large Vessel Occlusion, Thanh N Nguyen, Raul G Nogueira, Muhammad M Qureshi, Simon Nagel, Jean Raymond, Mohamad Abdalkader, Jelle Demeestere, João Pedro Marto, Sunil A Sheth, Volker Puetz, Anne Dusart, Patrik Michel, Marc Ribo, Osama O Zaidat, James E Siegler, Diogo C Haussen, Daniel Strbian, Hilde Henon, Mahmoud H Mohammaden, Markus A Möhlenbruch, Marta Olive-Gadea, Ajit S Puri, Simon Winzer, Johannes Kaesmacher, Piers Klein, Liisa Tomppo, Francois Caparros, João Nuno Ramos, Mouhammad A Jumaa, Syed F Zaidi, Nicolas Martinez-Majander, Stefania Nannoni, Lieselotte Vandewalle, Flavio Bellante, Mudassir Farooqui, Sergio Salazar-Marioni, Pekka Virtanen, Daniel P O Kaiser, Anke Wouters, Rita Ventura, Jessica Jesser, Adnan Mujanovic, Liqi Shu, Alicia C Castonguay, Zain Mansoor, Zhongming Qiu, Hesham E Masoud, Manuel Requena, Erno Peltola, Wei Hu, Eugene Lin, Kanta Tanaka, Charlotte Cordonnier, Daniel Roy, Shadi Yaghi, Davide Strambo, Hiroshi Yamagami, Urs Fischer, Tudor G Jovin, Robin Lemmens, Peter A Ringleb, Santiago Ortega-Gutierrez

Faculty, Staff and Student Publications

Background and objectives: There is uncertainty whether patients with large vessel occlusion (LVO) presenting in the late 6-hour to 24-hour time window can be selected for endovascular therapy (EVT) by noncontrast CT (NCCT) and CT angiography (CTA) for LVO detection. We evaluated the clinical outcomes of patients selected for EVT by NCCT compared with those medically managed in the extended time window.

Methods: This multinational cohort study was conducted at 66 sites across 10 countries. Consecutive patients with proximal anterior LVO stroke selected for EVT by NCCT or medically managed and presenting within 6-24 hours of time last seen well …

Thbs1 Regulates Skeletal Muscle Mass In A Tgfβ-Smad2/3-Atf4-Dependent Manner, Davy Vanhoutte, Tobias G Schips, Rachel A Minerath, Jiuzhou Huo, Naga Swathi Sree Kavuri, Vikram Prasad, Suh-Chin Lin, Michael J Bround, Michelle A Sargent, Christopher M Adams, Jeffery D Molkentin

Faculty, Staff and Students Publications

Loss of muscle mass is a feature of chronic illness and aging. Here, we report that skeletal muscle-specific thrombospondin-1 transgenic mice (Thbs1 Tg) have profound muscle atrophy with age-dependent decreases in exercise capacity and premature lethality. Mechanistically, Thbs1 activates transforming growth factor β (TGFβ)-Smad2/3 signaling, which also induces activating transcription factor 4 (ATF4) expression that together modulates the autophagy-lysosomal pathway (ALP) and ubiquitin-proteasome system (UPS) to facilitate muscle atrophy. Indeed, myofiber-specific inhibition of TGFβ-receptor signaling represses the induction of ATF4, normalizes ALP and UPS, and partially restores muscle mass in Thbs1 Tg mice. Similarly, myofiber-specific deletion of Smad2 and Smad3 …

Astrocytic Slc4a4 Regulates Blood-Brain Barrier Integrity In Healthy And Stroke Brains Via A Ccl2-Ccr2 Pathway And No Dysregulation, Qi Ye, Juyeon Jo, Chih-Yen Wang, Heavin Oh, Jiangshan Zhan, Tiffany J Choy, Kyoung In Kim, Angelo D'Alessandro, Yana K Reshetnyak, Sung Yun Jung, Zheng Chen, Sean P Marrelli, Hyun Kyoung Lee

Faculty, Staff and Student Publications

Astrocytes play vital roles in blood-brain barrier (BBB) maintenance, yet how they support BBB integrity under normal or pathological conditions remains poorly defined. Recent evidence suggests that ion homeostasis is a cellular mechanism important for BBB integrity. In the current study, we investigated the function of an astrocyte-specific pH regulator, Slc4a4, in BBB maintenance and repair. We show that astrocytic Slc4a4 is required for normal astrocyte morphological complexity and BBB function. Multi-omics analyses identified increased astrocytic secretion of CCL2 coupled with dysregulated arginine-NO metabolism after Slc4a4 deletion. Using a model of ischemic stroke, we found that loss of Slc4a4 exacerbates …

Smoking Cessation After Initial Treatment Failure With Varenicline Or Nicotine Replacement: A Randomized Clinical Trial, Paul M Cinciripini, Charles E Green, Sanjay Shete, Jennifer A Minnix, Jason D Robinson, Yong Cui, Seokhun Kim, George Kypriotakis, Diane Beneventi, Janice A Blalock, Francesco Versace, Maher Karam-Hage

Faculty, Staff and Student Publications

Importance: Most people who smoke do not quit on their initial attempt.

Objective: To determine the best subsequent strategy for nonabstinence following initial treatment with varenicline or combined nicotine replacement therapy (CNRT).

Design, setting, and participants: Using a double-blind, placebo-controlled, sequential multiple assignment randomized trial, 490 volunteers were randomized to receive 6 weeks of varenicline or CNRT. After 6 weeks, nonabstainers were rerandomized to continue, switch, or increase medication dosage for 6 additional weeks. The study was conducted from June 2015 through October 2019 in a Texas tobacco treatment clinic.

Interventions: The initial treatment was 2 mg/d of varenicline or …

Generation Of Oviductal Glycoprotein 1 Cre Mouse Model For The Study Of Secretory Epithelial Cells Of The Oviduct, Emily A Mcglade, Jiude Mao, Kalli K Stephens, Andrew M Kelleher, Lisette A Maddison, Miranda L Bernhardt, Francesco J Demayo, John P Lydon, Wipawee Winuthayanon

Faculty, Staff and Students Publications

The epithelial cell lining of the oviduct plays an important role in oocyte pickup, sperm migration, preimplantation embryo development, and embryo transport. The oviduct epithelial cell layer comprises ciliated and nonciliated secretory cells. The ciliary function has been shown to support gamete and embryo movement in the oviduct, yet secretory cell function has not been well characterized. Therefore, our goal was to generate a secretory cell-specific Cre recombinase mouse model to study the role of the oviductal secretory cells. A knock-in mouse model, Ovgp1Cre:eGFP, was created by expressing Cre from the endogenous Ovgp1 (oviductal glycoprotein 1) locus, with enhanced green …

Care Of The Critically Ill Nontrauma Patient: Improving Emergency Department Readiness And Patient Care Through The Implementation Of A Dedicated Resuscitation Bay, Martha H. Buck Rn, Bsn, Tcrn

Doctor of Nursing Practice Final Manuscripts

Current best practice among emergency departments worldwide includes the maintenance of a dedicated resuscitation space. This practice allows for team members and equipment to be ready at a moment’s notice to provide care to a patient in need of lifesaving interventions. This evidence-based performance improvement project seeks to implement this standard of care in a busy, urban emergency department in Southern California.

Prior to this study, patients at this facility were placed in the next available care space, without the maintenance of a dedicated resuscitation area for critically ill patients. Survey data evaluating staff levels of perceived readiness to care …

Plasmonic Nano-Aperture Label-Free Imaging Of Single Small Extracellular Vesicles For Cancer Detection, Nareg Ohannesian, Mohammad Sadman Mallick, Jianzhong He, Yawei Qiao, Nan Li, Simona F Shaitelman, Chad Tang, Eileen H Shinn, Wayne L Hofstetter, Alexei Goltsov, Manal M Hassan, Kelly K Hunt, Steven H Lin, Wei-Chuan Shih

Faculty, Staff and Student Publications

BACKGROUND: Small extracellular vesicle (sEV) analysis can potentially improve cancer detection and diagnostics. However, this potential has been constrained by insufficient sensitivity, dynamic range, and the need for complex labeling.

METHODS: In this study, we demonstrate the combination of PANORAMA and fluorescence imaging for single sEV analysis. The co-acquisition of PANORAMA and fluorescence images enables label-free visualization, enumeration, size determination, and enables detection of cargo microRNAs (miRs).

RESULTS: An increased sEV count is observed in human plasma samples from patients with cancer, regardless of cancer type. The cargo miR-21 provides molecular specificity within the same sEV population at the single …

Clonal Evolution Of Hematopoietic Stem Cells After Cancer Chemotherapy, Hidetaka Uryu, Koichi Saeki, Hiroshi Haeno, Chiraag Deepak Kapadia, Ken Furudate, Jyoti Nangalia, Michael Spencer Chapman, Li Zhao, Joanne I Hsu, Chong Zhao, Shujuan Chen, Tomoyuki Tanaka, Zongrui Li, Hui Yang, Courtney Dinardo, Naval Daver, Naveen Pemmaraju, Nitin Jain, Farhad Ravandi, Jianhua Zhang, Xingzhi Song, Erika Thompson, Hongli Tang, Latasha Little, Curtis Gumbs, Robert Z Orlowski, Muzaffar Qazilbash, Kapil Bhalla, Simona Colla, Hagop Kantarjian, Rashmi Kanagal Shamanna, Carlos Bueso- Ramos, Daisuke Nakada, P Andrew Futreal, Elizabeth Shpall, Margaret Goodell, Guillermo Garcia-Manero, Koichi Takahashi

Faculty, Staff and Students Publications

Normal hematopoietic stem and progenitor cells (HSPCs) inherently accumulate somatic mutations and lose clonal diversity with age, processes implicated in the development of myeloid malignancies 1 . The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal HSPCs is not well defined. We conducted whole-genome sequencing on 1,032 single-cell-derived HSPC colonies from 10 patients with multiple myeloma (MM), who had undergone various chemotherapy regimens. Our findings reveal that melphalan treatment distinctly increases mutational burden with a unique mutation signature, whereas other MM chemotherapies do not significantly affect the normal mutation rate of …

Androgen Deprivation Induces Neuroendocrine Phenotypes In Prostate Cancer Cells Through Creb1/Ezh2-Mediated Downregulation Of Rest, Dayong Zheng, Yan Zhang, Sukjin Yang, Ning Su, Michael Bakhoum, Guoliang Zhang, Samira Naderinezhad, Zhengmei Mao, Zheng Wang, Ting Zhou, Wenliang Li

Faculty, Staff and Student Publications

Although effective initially, prolonged androgen deprivation therapy (ADT) promotes neuroendocrine differentiation (NED) and prostate cancer (PCa) progression. It is incompletely understood how ADT transcriptionally induces NE genes in PCa cells. CREB1 and REST are known to positively and negatively regulate neuronal gene expression in the brain, respectively. No direct link between these two master neuronal regulators has been elucidated in the NED of PCa. We show that REST mRNA is downregulated in NEPC cell and mouse models, as well as in patient samples. Phenotypically, REST overexpression increases ADT sensitivity, represses NE genes, inhibits colony formation in culture, and xenograft tumor …

Endothelial Dysfunction Linked To Ventricular Dysfunction In Children With Sickle Cell Disease, A 3d Speckle Tracking Study., Antoine Abdelmassih, Mervat Haroun, Rasha Abdelraouf Abdelaziz Afifi, Gehan Hussein, Manal Abdelhameed, Marina George Asaad, Heba Tarabeh, Nourhan Essam El Din Taha, Nourine Diab, Noura Shebl, Raghda Fouda, Marianne Edward Yassa, Mohamed Ghobashy, Hala Agha

Journal of the Saudi Heart Association

Background

Sickle Cell Disease (SCD) is not a hematologic disease that occurs in isolation; it results in multi-organ complications. There is growing evidence of vascular stiffness as its underlying cause.

This study aimed to investigate the relationship between endothelial stiffness and LV dysfunction in SCD patients and to explore its pathophysiology, particularly regarding the depletion of vasodilators such as Nitric Oxide (NO).

Methodology

32 patients with established criteria for SCD and 40 healthy control subjects were selected for this case-control study. Comprehensive clinical assessment and assessment of endothelial function using Brachial Flow-mediated dilation (FMD) were performed, along with serum NO …

Legal Outcomes Of Litigation After Iatrogenic Genitourinary Trauma, Helen H. Sun, Crystal An, Andrew Drozd, Nicholas Sellke, Kimberly Tay, Kirtishri Mishra, Kyle Scarberry, Shubham Gupta, Nannan Thirumavalavan

Researchers, Instructors, & Staff Scholarship

Objective: To evaluate plaintiff and defendant characteristics associated with iatrogenic genitourinary (GU) trauma litigation and outcomes of closed claims. Methods: LexisNexis was queried in April 2023 using terms related to GU organs and injury, and manually reviewed for iatrogenic cases. Case details including defendant, organ involvement, and legal outcome were obtained. Multinomial regression analysis was performed to identify factors associated with outcome. Results: Four hundred ten cases involving 611 defendants were identified, with the ureter the most commonly affected organ (202/410, 49.3%). Most cases involved adult plaintiffs (380, 92.7%) and resulted in favor of the defense (227, 55.4%). Injuries resulted …

Increased Usage Of Doxycycline For Young Children With Lyme Disease, Amy Thompson, Desiree Neville, Laura Chapman, Fran Balamuth, Meagan Ladell, Anupam Kharbanda, Rachael Aresco, Lise Nigrovic

Department of Emergency Medicine Faculty Papers

Background: The 2018 Infectious Disease Committee of the American Academy of Pediatrics stated that up to 3 weeks or less of doxycycline is safe in children of all ages. Our goal was to examine trends in doxycycline treatment for children with Lyme disease.

Methods: We assembled a prospective cohort of children aged 1 to 21 years with Lyme disease who presented to one of eight participating Pedi Lyme Net centers between 2015 and 2023. We defined a Lyme disease case with an erythema migrans (EM) lesion or positive two-tier Lyme disease serology categorized by stage: early-localized (single EM lesion), early-disseminated …

Selective Refueling Of Car T Cells Using Ada1 And Cd26 Boosts Antitumor Immunity, Yue Hu, Abhijit Sarkar, Kevin Song, Sara Michael, Magnus Hook, Ruoning Wang, Andras Heczey, Xiaotong Song

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) T cell therapy is hindered in solid tumor treatment due to the immunosuppressive tumor microenvironment and suboptimal T cell persistence. Current strategies do not address nutrient competition in the microenvironment. Hence, we present a metabolic refueling approach using inosine as an alternative fuel. CAR T cells were engineered to express membrane-bound CD26 and cytoplasmic adenosine deaminase 1 (ADA1), converting adenosine to inosine. Autocrine secretion of ADA1 upon CD3/CD26 stimulation activates CAR T cells, improving migration and resistance to transforming growth factor β1 suppression. Fusion of ADA1 with anti-CD3 scFv further boosts inosine production and minimizes tumor …

Comprehensive In Vitro And In Vivo Evaluation Of Therapeutic Potential Of Bacopa-Derived Asiatic Acid Against A Human Oral Pathogen Streptococcus Mutans, Rajendran Jeyasri, Pandiyan Muthuramalingam, Arumugam Priya, Rajaiah Alexpandi, N. R. Siva Shanmugam, Saminathan Nivetha, Hyunsuk Shin, Shunmugiah Karutha Pandian, Arumugam Veera Ravi, Manikandan Ramesh

Food for Health: Publications

Dental caries is a common human oral disease worldwide, caused by an acid-producing bacteria Streptococcus mutans. The use of synthetic drugs and antibiotics to prevent dental caries has been increasing, but this can lead to severe side effects. To solve this issue, developing and developed countries have resorted to herbal medicines as an alternative to synthetic drugs for the treatment and prevention of dental caries. Therefore, there is an urgent need for plant-derived products to treat such diseases. Bacopa monnieri, a well-documented medicinal plant, contains 52 phytocompounds, including the pentacyclic triterpenoid metabolite known as asiatic acid (ASTA). Hence, …

Il-2-Free Tumor-Infiltrating Lymphocyte Therapy With Pd-1 Blockade Demonstrates Potent Efficacy In Advanced Gynecologic Cancer, Jing Guo, Chunyan Wang, Ning Luo, Yuliang Wu, Wei Huang, Jihui Zhu, Weihui Shi, Jinye Ding, Yao Ge, Chunhong Liu, Zhen Lu, Robert C Bast, Guihai Ai, Weihong Yang, Rui Wang, Caixia Li, Rong Chen, Shupeng Liu, Huajun Jin, Binghui Zhao, Zhongping Cheng

Faculty, Staff and Student Publications

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer.

METHODS: Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, …

Developing A Membrane-Proximal Cd33-Targeting Car T Cell, Ruby Freeman, Sanam Shahid, Abdul G Khan, Serena C Mathew, Sydney Souness, Erin R Burns, Jasmine S Um, Kento Tanaka, Winson Cai, Sarah Yoo, Andrew Dunbar, Young Park, Devin Mcavoy, Kinga K Hosszu, Ross L Levine, Jaap Jan Boelens, Ivo C Lorenz, Renier J Brentjens, Anthony F Daniyan

Faculty, Staff and Student Publications

BACKGROUND: CD33 is a tractable target in acute myeloid leukemia (AML) for chimeric antigen receptor (CAR) T cell therapy, but clinical success is lacking.

METHODS: We developed 3P14HLh28Z, a novel CD33-directed CD28/CD3Z-based CAR T cell derived from a high-affinity binder obtained through membrane-proximal fragment immunization in humanized mice.

RESULTS: We found that immunization exclusively with the membrane-proximal domain of CD33 is necessary for identification of membrane-proximal binders in humanized mice. Compared with clinically validated lintuzumab-based CAR T cells targeting distal CD33 epitopes, 3P14HLh28Z showed enhanced in vitro functionality as well as superior tumor control and increased overall survival in both …

Enhancing Peripartum Care Through Standardized Nurse Knowledge Exchange, Gabriela Ochoa

Master's Projects and Capstones

Problem Inconsistent handoff practices during patient transfers can cause mistakes and adverse outcomes. Hospital A's peripartum unit has no set policy for Nurse Knowledge Exchange (NKE) during transfers. This project will introduce a standard handoff guide to enhance communication and prevent harmful results after patient transfers.

Context The quality improvement project was conducted in a peripartum mesosystem within an urban hospital in Northern California. This specific area of the hospital comprised 21 postpartum rooms and nine laboring rooms.

Intervention The project involved a methodical strategy that encompassed engaging stakeholders, conducting a literature review, and analyzing data to pinpoint areas for …

Development Of An Endometriosis Toolkit To Support Clinicians In Providing Quality Care For Women, Rachel Hasbun

Doctor of Nursing Practice (DNP) Projects

Abstract

Background: Endometriosis is the abnormal growth of endometrium-like tissue outside the uterine cavity, affecting approximately 11% of women in the United States during their reproductive years. Diagnostic challenges stem from its varied clinical presentations, reliance on laparoscopy for definitive diagnosis, and limited awareness among practitioners and patients, potentially leading to diagnostic delays of up to 13 years.

Problem: The complexities of diagnosing endometriosis in primary care and specialty settings, combined with limited provider awareness and a lack of comprehensive resources, hinder timely and accurate identification. This leads to suboptimal treatment and care for women affected by the condition.

Methods: …

Selective And Brain-Penetrant Acss2 Inhibitors Target Breast Cancer Brain Metastatic Cells, Emily Esquea, Lorela Ciraku, Riley Young, Jessica Merzy, Alexandra Talarico, Nusaiba Ahmed, Mangalam Karuppiah, Anna Ramesh, Adam Chatoff, Claudia Crispim, Adel Rashad, Simon Cocklin, Nathaniel Snyder, Joris Beld, Nicole Simone, Mauricio Reginato, Alexej Dick

Kimmel Cancer Center Faculty Papers

Breast cancer brain metastasis (BCBM) typically results in an end-stage diagnosis and is hindered by a lack of brain-penetrant drugs. Tumors in the brain rely on the conversion of acetate to acetyl-CoA by the enzyme acetyl-CoA synthetase 2 (ACSS2), a key regulator of fatty acid synthesis and protein acetylation. Here, we used a computational pipeline to identify novel brain-penetrant ACSS2 inhibitors combining pharmacophore-based shape screen methodology with absorption, distribution, metabolism, and excretion (ADME) property predictions. We identified compounds AD-5584 and AD-8007 that were validated for specific binding affinity to ACSS2. Treatment of BCBM cells with AD-5584 and AD-8007 leads to …

Desvenlafaxine Induced Acute Angle-Closure Glaucoma - Case Report, Venkatesh Babu Dr, Priyankha Kothandaraman Dr, Megha Sadashiv Dr., Kishor M

Digital Journal of Clinical Medicine

The World Health Organization (WHO) estimates that Depressive disorder affects more than 264 million people worldwide. The global prevalence of depression among those who are aged 18 years and older was approximately 4.4%. According to a 2017 study by India's National Institute of Mental Health and Neuroscience s (NIMHANS), 7.5% of the population in the nation suffers from depression affecting one in 20 Indians_[1].

SSRIs ( Selective Serotonin Re uptake Inhibitors) and SNRIs ( serotonin-nor epinephrine re uptake inhibitors) are increasingly the first-line choices of anti-depressant because of their tolerable side-effect profile and low rate of lethality if …

Enhancer Switching In Cell Lineage Priming Is Linked To Erna, Brg1’S At-Hook, And Swi/Snf Recruitment, Dhurjhoti Saha, Srinivas Animireddy, Junwoo Lee, Anna Thommen, Mckenzie M Murvin, Yue Lu, J Mauro Calabrese, Blaine Bartholomew

Faculty, Staff and Student Publications

RNA transcribed from enhancers, i.e., eRNA, has been suggested to directly activate transcription by recruiting transcription factors and co-activators. Although there have been specific examples of eRNA functioning in this way, it is not clear how general this may be. We find that the AT-hook of SWI/SNF preferentially binds RNA and, as part of the esBAF complex, associates with eRNA transcribed from intronic and intergenic regions. Our data suggest that SWI/SNF is globally recruited in cis by eRNA to cell-type-specific enhancers, representative of two distinct stages that mimic early mammalian development, and not at enhancers that are shared between the …

Unraveling Etc Complex I Function In Ferroptosis Reveals A Potential Ferroptosis-Inducing Therapeutic Strategy For Lkb1-Deficient Cancers, Chao Mao, Guang Lei, Amber Horbath, Min Wang, Zhengze Lu, Yuelong Yan, Xiaoguang Liu, Lavanya Kondiparthi, Xiong Chen, Jun Cheng, Qidong Li, Zhihao Xu, Li Zhuang, Bingliang Fang, Joseph R Marszalek, Masha V Poyurovsky, Kellen Olszewski, Boyi Gan

Faculty, Staff and Student Publications

The role of the mitochondrial electron transport chain (ETC) in regulating ferroptosis is not fully elucidated. Here, we reveal that pharmacological inhibition of the ETC complex I reduces ubiquinol levels while decreasing ATP levels and activating AMP-activated protein kinase (AMPK), the two effects known for their roles in promoting and suppressing ferroptosis, respectively. Consequently, the impact of complex I inhibitors on ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibition is limited. The pharmacological inhibition of complex I in LKB1-AMPK-inactivated cells, or genetic ablation of complex I (which does not trigger apparent AMPK activation), abrogates the AMPK-mediated ferroptosis-suppressive effect and sensitizes …

Optical Coherence Tomography-Guided Brillouin Microscopy Highlights Regional Tissue Stiffness Differences During Anterior Neural Tube Closure In The Mthfd1l Murine Mutant, Yogeshwari S Ambekar, Carlo Donato Caiaffa, Bogdan J Wlodarczyk, Manmohan Singh, Alexander W Schill, John W Steele, Jitao Zhang, Salavat R Aglyamov, Giuliano Scarcelli, Richard H Finnell, Kirill V Larin

Faculty, Staff and Students Publications

Neurulation is a highly synchronized biomechanical process leading to the formation of the brain and spinal cord, and its failure leads to neural tube defects (NTDs). Although we are rapidly learning the genetic mechanisms underlying NTDs, the biomechanical aspects are largely unknown. To understand the correlation between NTDs and tissue stiffness during neural tube closure (NTC), we imaged an NTD murine model using optical coherence tomography (OCT), Brillouin microscopy and confocal fluorescence microscopy. Here, we associate structural information from OCT with local stiffness from the Brillouin signal of embryos undergoing neurulation. The stiffness of neuroepithelial tissues in Mthfd1l null embryos …

Optical Coherence Tomography-Guided Brillouin Microscopy Highlights Regional Tissue Stiffness Differences During Anterior Neural Tube Closure In The Mthfd1l Murine Mutant, Yogeshwari S Ambekar, Carlo Donato Caiaffa, Bogdan J Wlodarczyk, Manmohan Singh, Alexander W Schill, John W Steele, Jitao Zhang, Salavat R Aglyamov, Giuliano Scarcelli, Richard H Finnell, Kirill V Larin

Faculty, Staff and Students Publications

Neurulation is a highly synchronized biomechanical process leading to the formation of the brain and spinal cord, and its failure leads to neural tube defects (NTDs). Although we are rapidly learning the genetic mechanisms underlying NTDs, the biomechanical aspects are largely unknown. To understand the correlation between NTDs and tissue stiffness during neural tube closure (NTC), we imaged an NTD murine model using optical coherence tomography (OCT), Brillouin microscopy and confocal fluorescence microscopy. Here, we associate structural information from OCT with local stiffness from the Brillouin signal of embryos undergoing neurulation. The stiffness of neuroepithelial tissues in Mthfd1l null embryos …

Transcriptomic Profiling Of Plasma Extracellular Vesicles Enables Reliable Annotation Of The Cancer-Specific Transcriptome And Molecular Subtype, Vahid Bahrambeigi, Jaewon J Lee, Vittorio Branchi, Kimal I Rajapakshe, Zhichao Xu, Naishu Kui, Jason T Henry, Wang Kun, Bret M Stephens, Sarah Dhebat, Mark W Hurd, Ryan Sun, Peng Yang, Eytan Ruppin, Wenyi Wang, Scott Kopetz, Anirban Maitra, Paola A Guerrero

Faculty, Staff and Student Publications

Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved transcriptomes of RNA within plasma extracellular vesicles (evRNA), we successfully predicted consensus molecular subtypes in patients with metastatic colorectal cancer. Analysis of plasma evRNA also enabled monitoring of changes in transcriptomic subtype under treatment selection pressure and identification of molecular pathways associated with recurrence. This approach …