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Cultivating Compassion: A Cross-Sectional Evaluation Of Empathy Among Medical Undergraduate Students, Anchu R Nath, Ishika Jindal, Nayanabai Shabadi, Sunil Kumar D

Digital Journal of Clinical Medicine

ABSTRACT:

BACKGROUND: Empathy plays a crucial role in medical practice, profoundly affecting patient outcomes and treatment. Understanding the factors that influence empathy among medical students can help in developing strategies to enhance empathetic skills during medical training. This study aims to evaluate the correlates of empathy among medical undergraduate students using an epidemiological cross-sectional design.

MATERIALS AND METHODS:

A cross-sectional study was conducted among 270 medical undergraduate students from various academic years at JSS Medical College for four months (September 2023-December 2023). Convenient sampling was used to select study participants. Participants completed a standardized empathy questionnaire, the Jefferson Scale …

A Review Of Managing Catastrophes In Robotic-Assisted Thoracic Surgery, Shamele Battan-Wraith, Kevin Wang, Ahmed Elkamel, Kameron Durante, Hope Conrad, Kayla Iannarelli, Olugbenga Okusanya, Praveen Sridhar, Stephanie G. Worrell

Department of Surgery Faculty Papers

Lung cancer is the most commonly diagnosed cancer worldwide in 2022, with over 2.5 million new cases, or 1 in 8 of all cancers diagnosed worldwide. Lung cancer is the leading cause of cancer related mortality in the United States, with non-small cell lung cancer (NSCLC) being the most prevalent type. For early-stage NSCLC, lung resection with anatomic lobectomy remains the standard of care. Robot-assisted lobectomy is gaining popularity over video-assisted thoracoscopic surgery (VATS) and open thoracotomy due to improved visualization, ergonomics, and instrumentation. Despite these advancements, intraoperative complications and a steep learning curve present significant barriers to the widespread …

Nos Inhibition Sensitizes Metaplastic Breast Cancer To Pi3k Inhibition And Taxane Therapy Via C-Jun Repression, Tejaswini Reddy, Akshjot Puri, Liliana Guzman-Rojas, Christoforos Thomas, Wei Qian, Jianying Zhou, Hong Zhao, Bijan Mahboubi, Adrian Oo, Young-Jae Cho, Baek Kim, Jose Thaiparambil, Roberto Rosato, Karina Ortega Martinez, Maria Florencia Chervo, Camila Ayerbe, Noah Giese, David Wink, Stephen Lockett, Stephen Wong, Jeffrey Chang, Savitri Krishnamurthy, Clinton Yam, Stacy Moulder, Helen Piwnica-Worms, Funda Meric-Bernstam, Jenny Chang

Faculty, Staff and Student Publications

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane. Mechanistically, NOS blockade leads to a decrease in the S-nitrosylation of c-Jun NH

Orthogonal And Multiplexable Genetic Perturbations With An Engineered Prime Editor And A Diverse Rna Array, Qichen Yuan, Hongzhi Zeng, Tyler C Daniel, Qingzhuo Liu, Yongjie Yang, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Liliana M Abramson, Boyang Zhang, Yong Xu, Xue Gao

Faculty, Staff and Students Publications

Programmable and modular systems capable of orthogonal genomic and transcriptomic perturbations are crucial for biological research and treating human genetic diseases. Here, we present the minimal versatile genetic perturbation technology (mvGPT), a flexible toolkit designed for simultaneous and orthogonal gene editing, activation, and repression in human cells. The mvGPT combines an engineered compact prime editor (PE), a fusion activator MS2-p65-HSF1 (MPH), and a drive-and-process multiplex array that produces RNAs tailored to different types of genetic perturbation. mvGPT can precisely edit human genome via PE coupled with a prime editing guide RNA and a nicking guide RNA, activate endogenous gene expression …

Age-Dependent Regulation Of Axoglial Interactions And Behavior By Oligodendrocyte Ankyring, Xiaoyun Ding, Yu Wu, Anna Vainshtein, Victoria Rodriguez, Emily Ricco, James T Okoh, Yanhong Liu, Daniel C Kraushaar, Elior Peles, Matthew N Rasband

Faculty, Staff and Students Publications

The bipolar disorder (BD) risk gene ANK3 encodes the scaffolding protein AnkyrinG (AnkG). In neurons, AnkG regulates polarity and ion channel clustering at axon initial segments and nodes of Ranvier. Disruption of neuronal AnkG causes BD-like phenotypes in mice. During development, AnkG is also expressed at comparable levels in oligodendrocytes and facilitates the efficient assembly of paranodal junctions. However, the physiological roles of glial AnkG in the mature nervous system, and its contributions to BD-like phenotypes, remain unexplored. Here, we show that oligodendroglia-specific AnkG conditional knockout results in destabilization of axoglial interactions in aged but not young adult mice. In …

Role Of Nf2 Mutation In The Development Of Eleven Different Cancers, Shervin Hosseingholi Nouri, Vijay Nitturi, Elizabeth Ledbetter, Collin W English, Sean Lau, Tiemo J Klisch, Akash J Patel

Faculty, Staff and Students Publications

Background/Objectives: With the rise in prevalence of diagnostic genetic techniques like RNA sequencing and whole exome sequencing (WES), as well as biological treatment regiments for cancer therapy, several genes have been implicated in carcinogenesis. This review aims to update our understanding of the Neurofibromatosis 2 (NF2) gene and its role in the pathogenesis of various cancers. Methods: A comprehensive search of five online databases yielded 43 studies that highlighted the effect of sporadic NF2 mutations on several cancers, including sporadic meningioma, ependymoma, schwannoma, mesothelioma, breast cancer, hepatocellular carcinoma, prostate cancer, glioblastoma, thyroid cancer, and melanoma. Of note were key biological …

Parp Inhibition Radiosensitizes Brca1 Wildtype And Mutated Breast Cancer To Proton Therapy, Mariam Ben Kacem, Scott J Bright, Emma Moran, David B Flint, David K J Martinus, Broderick X Turner, Ilsa Qureshi, Rishab Kolachina, Mandira Manandhar, Poliana C Marinello, Simona F Shaitelman, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Aggressive breast cancers often fail or acquire resistance to radiotherapy. To develop new strategies to improve the outcome of aggressive breast cancer patients, we studied how PARP inhibition radiosensitizes breast cancer models to proton therapy, which is a radiotherapy modality that generates more DNA damage in the tumor than standard radiotherapy using photons. Two human BRCA1-mutated breast cancer cell lines and their isogenic BRCA1-recovered pairs were treated with a PARP inhibitor and irradiated with photons or protons. Protons (9.9 and 3.85 keV/µm) induced higher cell kill independent of BRCA1 status. PARP inhibition amplified the cell kill effect to both photons …

Cancer Organoids As Reliable Disease Models To Drive Clinical Development Of Novel Therapies, Giovanni Blandino, Ronit Satchi-Fainaro, Ingeborg Tinhofer, Giovanni Tonon, Sarah C Heilshorn, Yong-Jun Kwon, Ana Pestana, Carlotta Frascolla, Luca Pompili, Aurora Puce, Sara Iachettini, Annalisa Tocci, Sofia Karkampouna, Marianna Kruithof-De Julio, Piera Tocci, Nicla Porciello, Klizia Maccaroni, Daniela Rutigliano, Xiling Shen, Gennaro Ciliberto

Faculty, Staff and Student Publications

On September 23-24 (2024) the 6th Workshop IRE on Translational Oncology, titled "Cancer Organoids as Reliable Disease Models to Drive Clinical Development of Novel Therapies," took place at the IRCCS Regina Elena Cancer Institute in Rome. This prominent international conference focused on tumor organoids, bringing together leading experts from around the world.A central challenge in precision oncology is modeling the dynamic tumor ecosystem, which encompasses numerous elements that evolve spatially and temporally. Patient-derived 3D culture models, including organoids, explants, and engineered or bioprinted systems, have recently emerged as sophisticated tools capable of capturing the complexity and diversity of cancer cells …

Factors Affecting Waiting Times To Enter Opioid Use Disorder Treatment In The United States With A Particular Focus On Potential Biological Sex Disparity, Stanley Nkemjika, Kenneth Oforeh, Connie Olwit, Olaniyi Olayinka, Terence Tumenta

Department of Psychiatry and Human Behavior Faculty Papers

AIM: Opioid use disorder (OUD) is the problematic use of licit or illicit opioids. Thus far, the literature on biological sex differences in accessing treatment is scarce. Hence, we hypothesize that biological sex has a moderating effect on OUD treatment accessibility. We aim to explore biological sex differences in treatment disparities and its role in wait time to enter OUD treatment.

METHOD: Using the 2018 Treatment Episode Data Set Discharge, the national sample representative of OUD patients in the substance use disorder treatment facilities within the 50 states of the United States was 382,547. Univariate and multivariable logistic analysis of …

Optimizing Ewing Sarcoma And Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement, Matthew S Dietz, Alyaa Al-Ibraheemi, Jessica L Davis, C Matthew Hawkins, Brian T Craig, Roshni Dasgupta, David S Geller, David S Shulman, Sarah Cohen-Gogo, Ajay Gupta, Susan L Whiteway, Emily K Slotkin, Christine M Heske, Safia K Ahmed, Daniel J Indelicato, Catherine M Albert, Nicole Montgomery, Jesse K Sandberg, Holcombe E Grier, Mark Krailo, Michael S Isakoff, Elyssa Rubin, Elizabeth R Lawlor, Steven G Dubois, Leo Mascarenhas, Patrick J Grohar, Odion Binitie, Damon Reed, Katherine Janeway, Ryan D Roberts, Kelly M Bailey

Faculty, Staff and Students Publications

Trends in diagnostic biopsy sample collection approaches for primary bone sarcomas have shifted in the past 2 decades. Although open/incisional biopsies used to be the predominant approach to obtain diagnostic material for Ewing sarcoma and osteosarcoma, image-guided core needle biopsies have increased in frequency and are safe for patients. These procedures are less invasive and reduce recovery times but have potential limitations. The quantity and quality of tissue obtained through these procedures vary between institutions. Acquired viable tissue volumes can be low, limiting the conduct of downstream expanded clinical workup, molecular analyses, and research. Patients with advanced Ewing sarcoma and …

Stem Cell Activity-Coupled Suppression Of Endogenous Retrovirus Governs Adult Tissue Regeneration, Ying Lyu, Soo Jin Kim, Ericka S Humphrey, Richa Nayak, Yinglu Guan, Qingnan Liang, Kun Hee Kim, Yukun Tan, Jinzhuang Dou, Huandong Sun, Xingzhi Song, Priyadharsini Nagarajan, Kamryn N Gerner-Mauro, Kevin Jin, Virginia Liu, Rehman H Hassan, Miranda L Johnson, Lisa P Deliu, Yun You, Anurag Sharma, H Amalia Pasolli, Yue Lu, Jianhua Zhang, Vakul Mohanty, Ken Chen, Youn Joo Yang, Taiping Chen, Yejing Ge

Faculty, Staff and Student Publications

Mammalian retrotransposons constitute 40% of the genome. During tissue regeneration, adult stem cells coordinately repress retrotransposons and activate lineage genes, but how this coordination is controlled is poorly understood. Here, we observed that dynamic expression of histone methyltransferase SETDB1 (a retrotransposon repressor) closely mirrors stem cell activities in murine skin. SETDB1 ablation leads to the reactivation of endogenous retroviruses (ERVs, a type of retrotransposon) and the assembly of viral-like particles, resulting in hair loss and stem cell exhaustion that is reversible by antiviral drugs. Mechanistically, at least two molecularly and spatially distinct pathways are responsible: antiviral defense mediated by hair …

High Peripheral T Cell Diversity Is Associated With Lower Risk Of Toxicity And Superior Response To Dual Immune Checkpoint Inhibitor Therapy In Patients With Metastatic Nsclc, Mehmet Altan, Ruoxing Li, Ziyi Li, Runzhe Chen, Ajay Sheshadri, Hai T Tran, Latasha Little, Joshua Baguley, Jefferson Sinson, Natalie Vokes, Saumil Gandhi, Mara B Antonoff, Stephen G Swisher, Greg Lizee, Alexandre Reuben, John V Heymach, Jianjun Zhang

Faculty, Staff and Student Publications

INTRODUCTION: Despite significant successes, immune checkpoint blockade fails to achieve clinical responses in a significant proportion of patients, predictive markers for responses are imperfect and immune-related adverse events (irAEs) are unpredictable. We used T-cell receptor (TCR) sequencing to systematically analyze prospectively collected patient blood samples from a randomized clinical trial of dual immune checkpoint inhibitor therapy to evaluate changes in the T-cell repertoire and their association with response and irAEs.

METHODS: Patients with immunotherapy-naïve metastatic non-small cell lung cancer (NSCLC) were treated with ipilimumab and nivolumab according to trial protocol (LONESTAR, NCT03391869). Blood samples were systematically obtained at baseline (n=107), …

Glucose-Lowering Agents Developed In The Last Two Decades And Their Perioperative Implications, Basavana Goudra, Geno Merli, Michael Green

Department of Anesthesiology Faculty Papers

The last two decades have provided far more options f both patients and their physicians in the treatment of diabetes mellitus. While dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been approved for nearly two decades, sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are relatively new. Of interest to perioperative physicians, these drugs present specific perioperative concerns, prompting many societies to issue guidelines. Retained gastric contents due to slow gastric emptying is a significant drawback of GLP-1RAs, increasing the risk of aspiration. Recommendations include withholding GLP-1RAs for a predefined period of time, performing gastric ultrasound to evaluate gastric …

Targeted Degradation Of Oncogenic Krasg12v Triggers Antitumor Immunity In Lung Cancer Models, Dezhi Li, Ke Geng, Yuan Hao, Jiajia Gu, Saurav Kumar, Annabel T Olson, Christina C Kuismi, Hye Mi Kim, Yuanwang Pan, Fiona Sherman, Asia M Williams, Yiting Li, Fei Li, Ting Chen, Cassandra Thakurdin, Michela Ranieri, Mary Meynardie, Daniel S Levin, Janaye Stephens, Alison Chafitz, Joy Chen, Mia S Donald-Paladino, Jaylen M Powell, Ze-Yan Zhang, Wei Chen, Magdalena Ploszaj, Han Han, Shengqing Stan Gu, Tinghu Zhang, Baoli Hu, Benjamin A Nacev, Medard Ernest Kaiza, Alice H Berger, Xuerui Wang, Jing Li, Xuejiao Sun, Yang Liu, Xiaoyang Zhang, Tullia C Bruno, Nathanael S Gray, Behnam Nabet, Kwok-Kin Wong, Hua Zhang

Faculty, Staff and Student Publications

Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most frequently mutated oncogene in lung adenocarcinoma, with G12C and G12V being the most predominant forms. Recent breakthroughs in KRASG12C inhibitors have transformed the clinical management of patients with the G12C mutation and advanced our understanding of the function of this mutation. However, little is known about the targeted disruption of KRASG12V, partly due to a lack of specific inhibitors. Here, we leverage the degradation tag (dTAG) system to develop a KRASG12V-transgenic mouse model. We explored the therapeutic potential of KRASG12V degradation and characterized its effect on the tumor microenvironment (TME). …

Inhibition Of Microrna-660-5p Decreases Breast Cancer Progression Through Direct Targeting Of Tmem41b, Valeria Villarreal-García, José Roberto Estupiñan-Jiménez, Vianey Gonzalez-Villasana, Pablo E Vivas-Mejía, Marienid Flores-Colón, Irma Estefanía Ancira-Moreno, Patricio Adrián Zapata-Morín, Claudia Altamirano-Torres, José Manuel Vázquez-Guillen, Cristina Rodríguez-Padilla, Recep Bayraktar, Mohamed H Rashed, Cristina Ivan, Gabriel Lopez-Berestein, Diana Reséndez-Pérez

Faculty, Staff and Student Publications

Background: Breast cancer is the most prevalent cancer among women worldwide. Most breast cancer-related deaths result from metastasis and drug resistance. Novel therapies are imperative for targeting metastatic and drug-resistant breast cancer cells. Accumulating evidence suggests that dysregulated microRNAs (miRNAs) promote breast cancer progression, metastasis, and drug resistance. Compared with healthy breast tissue, miR-660-5p is notably overexpressed in breast cancer tumor tissues. However, the downstream effectors of miR-660-5p in breast cancer cells have not been fully elucidated. Our aim was to investigate the role of miR-660-5p in breast cancer cell proliferation, migration, invasion, and angiogenesis and to identify its potential …

Phenotypic And Genetic Heterogeneity Of A Pakistani Cohort Of 15 Consanguineous Families Segregating Variants In Leber Congenital Amaurosis-Associated Genes, Zainab Akhtar, Sumaira Altaf, Yumei Li, Sana Bibi, Jamal Shah, Kiran Afshan, Meng Wang, Hafiz Muhammad Jafar Hussain, Nadeem Qureshi, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Background: Leber congenital amaurosis (LCA) is a congenital onset severe form of inherited retinal dystrophy (IRD) and a common cause of pediatric blindness. Disease-causing variants in at least 14 genes are reported to predispose LCA phenotype. LCA is inherited as an autosomal recessive disease. It can be an isolated eye disorder or as part of a syndrome, such as Senior Loken or Joubert syndrome. Sequencing studies from consanguineous populations have proven useful for novel variants identification; thus, the present study aimed to explore the genetic heterogeneity of 15 consanguineous Pakistani families, each segregating a severe IRD phenotype using targeted next …

Broad And Diverse Roles Of Sphingosine-1-Phosphate/Sphingosine-1-Phosphate Receptors In The Prostate., Daoquan Liu, Jianmin Liu, Yan Li, Lu Du, Qingqiong Cao, Liang Yang, Yongying Zhou, Ping Chen, Yuming Guo, Guang Zeng, Michael E. Disanto, Weidong Hu, Xinhua Zhang

Cooper Medical School of Rowan University Departmental Research

Benign prostatic hyperplasia (BPH) is a common condition in aging males, but its underlying pathogenesis remains unclear. Sphingosine-1-phosphate (S1P) and its receptors (S1PRs) play important roles in various diseases, while less studied in prostate. Current study attempts to clarify the expression and functional activities of S1P/S1PRs in the prostate. We discovered that S1P/S1PRs were richly expressed in the prostate, with S1PR1/2/3 localized in the epithelial/stromal compartments, while S1PR4/5 were less expressed. In vitro, S1P/S1PR1/S1PR3 promoted cell proliferation via AKT and ERK1/2 pathways, S1P/S1PR2/S1PR3 enhanced contraction of WPMY-1 cells and human prostate via RhoA/ROCK pathway, while S1P/S1PR1/S1PR2/S1PR3 alleviated the inflammation …

Effects On Maternal And Pregnancy Outcomes Of First-Trimester Malaria Infection Among Nulliparous Women From Kenya, Zambia, And The Democratic Republic Of The Congo, Sequoia I. Leuba, Daniel Westreich, Carl L. Bose, Andrew F. Olshan, Steve M. Taylor, Antoinette Tshefu, Adrien Lokangaka, Waldemar A. Carlo, Elwyn Chomba, Musaku Mwenechanya, Edward A. Liechty, Sherri L. Bucher, Osayame A. Ekhaguere, Fabian Esamai, Paul Nyongesa, Saleem Jessani, Sarah Saleem, Robert L. Goldenberg, Janet L. Moore, Tracy L. Nolen, Jennifer Hemingway-Foday, Elizabeth M. Mcclure, Marion Koso-Thomas, Richard Derman, Matthew Hoffman, Steven R. Meshnick, Melissa Bauserman

Department of Medicine Faculty Papers

BACKGROUND: Few studies have assessed the impact of first-trimester malaria infection during pregnancy. We estimated this impact on adverse maternal and pregnancy outcomes.

METHODS: In a convenience sample of women from the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated risk Reduction In Nulliparas) trial in Kenya, Zambia, and the Democratic Republic of the Congo, we tested for first-trimester Plasmodium falciparum infection using quantitative polymerase chain reaction. We estimated site-specific effects on pregnancy outcomes using parametric g-computation.

RESULTS: Compared to uninfected women, we observed the adjusted site-specific prevalence differences (PDs) among women with first-trimester malaria of the following pregnancy outcomes: preterm birth …

Biobehavioral Correlates Of Multidimensional Fatigue In Men With Prostate Cancer, Kristin Dickinson

Theses & Dissertations

The purpose of this thesis project was to 1) examine trajectories of multidimensional cancer-related fatigue (CRF) in men with prostate cancer during and after radiation treatment completion, and 2) identify biobehavioral correlates (demographic, clinical, co-occurring symptoms, and biologic [inflammatory cytokines]) for the different CRF dimensions.

Data for this secondary analysis were obtained from a descriptive, longitudinal IRB-approved study investigating men with non-metastatic prostate cancer receiving radiation therapy (RT). Data were obtained from 68 participant medical records, self-report questionnaires, and blood samples. Data were collected at: baseline (T1), completion of RT (T2), 6 months (T3) and 2 years (T4) after completion …

Protocol For Culturing Patient-Derived Organoids Of Cervical Cancer, Rui Wang, Timothy Harris, Dalissa Negrón-Figueroa, David Lo, Allison Judge, D'Shaunique Walters, Bo Jiang, Lauren E Colbert

Faculty, Staff and Student Publications

Herein, we present a protocol for culturing patient-derived organoids (PDOs) of cervical cancer that includes workflows for tumor biopsy/resection tissue and cytobrush-sampled cells. We describe steps for PDO culture initiation, including rinsing, gentle dissociation, Lymphoprep separation, and cell assessment, as well as seeding cells from surgical and cytobrush tissue digestion. We then provide guidance on PDO maintenance and passage and techniques for producing conditioned medium. Overall, this protocol serves as a valuable guide for establishing and maintaining cervical cancer PDOs. For complete details on the use and execution of this protocol, please refer to Colbert et al.

Mathematical Multi-Compartment Modeling Of Chronic Lymphocytic Leukemia Cell Kinetics Under Ibrutinib, Melanie Schulz, Sanne Bleser, Manouk Groels, Dragan Bošnački, Jan A Burger, Nicholas Chiorazzi, Carsten Marr

Faculty, Staff and Student Publications

The Bruton tyrosine kinase inhibitor ibrutinib is an effective treatment for patients with chronic lymphocytic leukemia (CLL). While it rapidly reduces lymph node and spleen size, it initially increases the number of lymphocytes in the blood due to cell redistribution. A previously published mathematical model described and quantified those cell kinetics. Here, we propose an alternative mechanistic model that outperforms the previous model in 26 of 29 patients. Our model introduces constant subcompartments for healthy lymphocytes and benign tissue and treats spleen and lymph nodes as separate compartments. This three-compartment model (comprising blood, spleen, and lymph nodes) performed significantly better …

Results Of The Simultaneous Combination Of Ponatinib And Blinatumomab In Philadelphia Chromosome-Positive All, Hagop Kantarjian, Nicholas J Short, Fadi G Haddad, Nitin Jain, Xuelin Huang, Guillermo Montalban-Bravo, Rashmi Kanagal-Shamanna, Tapan M Kadia, Naval Daver, Kelly Chien, Yesid Alvarado, Guillermo Garcia-Manero, Ghayas C Issa, Rebecca Garris, Cedric Nasnas, Lewis Nasr, Farhad Ravandi, Elias Jabbour

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In this analysis, we update our experience with the chemotherapy-free regimen of blinatumomab and ponatinib in 60 patients with newly diagnosed Philadelphia chromosome (Ph)-positive ALL. At a median follow-up of 24 months, the complete molecular response rate …

Protocol For Monitoring Clonal Hematopoiesis In Transgenic Mouse Models Using Multispectral Imaging, Priyanka Khanna, Lauren B Ostermann, Shayaun Khazaei, Ran Zhao, Michael Andreeff, Rasoul Pourebrahim

Faculty, Staff and Student Publications

Clonal hematopoiesis involves the clonal expansion of hematopoietic cells, potentially progressing into hematological malignancies. Here, we present a protocol for the development and characterization of two mouse models designed to simulate clonal hematopoiesis and acute myeloid leukemia. We describe steps for model generation, monitoring clonal expansion, harvesting, fixation, and staining of bone marrow and spleen tissues. We specifically focus on the visualization and analysis of p53 mutant clonal expansions, providing a comprehensive protocol for studying these phenomena in mouse models. For complete details on the use and execution of this protocol, please refer to Pourebrahim et al.

Womb, Gravity, And Space: Shifting Towards The Cerebellum-Basal Ganglia Paradigm In Dystonia, Diego Iacono

Department of Neurology Faculty Papers

No abstract provided.

Novel Digital Anomalies, Hippocampal Atrophy, And Mutations Expand The Genotypic And Phenotypic Spectra Of Cnksr2 In The Houge Type Of X-Linked Syndromic Intellectual Development Disorder (Mrxshg), Mohammad Reza Ghasemi, Sahand Tehrani Fateh, Afif Ben-Mahmoud, Vijay Gupta, Lara G. Stühn, Gaetan Lesca, Nicolas Chatron, Konrad Platzer, Patrick Edery, Hossein Sadeghi, Bertrand Isidor, Benjamin Cogné, Heidi L. Schulz, Ilona Krauspe-Stübecke, Radhakrishnan Periyasamy, Sheela Nampoothiri, Reza Mirfakhraie, Sahar Alijanpour, Steffen Syrbe, Ulrich Pfeifer, Stephanie Spranger, Kathrin Grundmann-Hauser, Tobias B. Haack, Maria T. Papadopoulou, Tayrine Da Silva Gonçalves, Eleni Panagiotakaki, Alexis Arzimanoglou, Seyed Hassan Tonekaboni, Yves Lacassie, Et Al

School of Medicine Faculty Publications

The Houge type of X-linked syndromic intellectual developmental disorder (MRXSHG) encompasses a spectrum of neurodevelopmental disorders characterized by intellectual disability (ID), language/speech delay, attention issues, and epilepsy. These conditions arise from hemizygous or heterozygous deletions, along with point mutations, affecting CNKSR2, a gene located at Xp22.12. CNKSR2, also known as CNK2 or MAGUIN, functions as a synaptic scaffolding molecule within the neuronal postsynaptic density (PSD) of the central nervous system. It acts as a link connecting postsynaptic structural proteins, such as PSD95 and S-SCAM, by employing multiple functional domains crucial for synaptic signaling and protein–protein interactions. Predominantly expressed in dendrites, …

Ifrd1 Is Required For Maintenance Of Bladder Epithelial Homeostasis, Bisiayo E Fashemi, Amala K Rougeau, Arnold M Salazar, Steven J Bark, Rayvanth Chappidi, Jeffrey W Brown, Charles J Cho, Jason C Mills, Indira U Mysorekar

Faculty, Staff and Students Publications

The maintenance of homeostasis and rapid regeneration of the urothelium following stress are critical for bladder function. Here, we identify a key role for IFRD1 in maintaining urothelial homeostasis in a mouse model. We demonstrate that the murine bladder expresses IFRD1 at homeostasis, particularly in the urothelium, and its loss alters the global transcriptome with significant accumulation of endolysosomes and dysregulated uroplakin expression pattern. We show that IFRD1 interacts with mRNA-translation-regulating factors in human urothelial cells. Loss of Ifrd1 leads to disrupted proteostasis, enhanced endoplasmic reticulum (ER stress) with activation of the PERK arm of the unfolded protein response pathway, …

Rna-Dependent Rna Polymerase Of Predominant Human Norovirus Forms Liquid-Liquid Phase Condensates As Viral Replication Factories, Soni Kaundal, Ramakrishnan Anish, B Vijayalakshmi Ayyar, Sreejesh Shanker, Gundeep Kaur, Sue E Crawford, Jeroen Pollet, Fabio Stossi, Mary K Estes, B V Venkataram Prasad

Faculty, Staff and Students Publications

Many viral proteins form biomolecular condensates via liquid-liquid phase separation (LLPS) to support viral replication and evade host antiviral responses, and thus, they are potential targets for designing antivirals. In the case of nonenveloped positive-sense RNA viruses, forming such condensates for viral replication is unclear and less understood. Human noroviruses (HuNoVs) are positive-sense RNA viruses that cause epidemic and sporadic gastroenteritis worldwide. Here, we show that the RNA-dependent RNA polymerase (RdRp) of pandemic GII.4 HuNoV forms distinct condensates that exhibit all the signature properties of LLPS with sustained polymerase activity and the capability of recruiting components essential for viral replication. …

The Camden Study - A Pregnancy Cohort Study Of Pregnancy Complications And Birth Outcomes In Camden, New Jersey, Usa., Stephanie Shiau, Xinhua Chen, Ayana April-Sanders, Ellen C Francis, Shristi Rawal, Megan Hansel, Kehinde Adeyemi, Zorimar Rivera-Núñez, Emily S Barrett

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Pregnancy is a unique stage of the life course characterized by trade-offs between the nutritional, immune, and metabolic needs of the mother and fetus. The Camden Study was originally initiated to examine nutritional status, growth, and birth outcomes in adolescent pregnancies and expanded to study dietary and molecular predictors of pregnancy complications and birth outcomes in young women.

METHODS: From 1985-2006, 4765 pregnant participants aged 12 years and older were recruited from Camden, NJ, one of the poorest cities in the US. The cohort reflects a population under-represented in perinatal cohort studies (45% Hispanic, 38% non-Hispanic Black, 17% White …

The Proteomics Of T-Cell And Early T-Cell Precursor (Etp) Acute Lymphocytic Leukemia: Prognostic Patterns In Adult And Pediatric-Etp All, Fieke W Hoff, Lourdes Sriraja, Yihua Qiu, Gaye N Jenkins, David T Teachey, Brent Wood, Meenakshi Devidas, Shaina Shockley, Mignon L Loh, Evangelia Petsalaki, Steven M Kornblau, Terzah M Horton

Faculty, Staff and Student Publications

Background: The 5-year overall survival (OS) rates of T-cell lymphocytic leukemia (T-ALL) are better for children (>90%) compared to adults (~57%). The early T-cell precursor (ETP) T-ALL subtype is prognostically unfavorable in adults, but less significant in pediatric T-ALL, and the diagnosis and prognosis of "near"-ETP is controversial. We compared protein and RNA expression patterns in pediatric and adult T-ALL to identify prognostic subgroups, and to further characterize ETP and near-ETP T-ALL in both age groups.

Methods: Protein expression was assessed using RPPA methodology for 321 target proteins in 361 T-ALL patient samples from 292 pediatrics and 69 adults, …

Enhancer Reprogramming Underlies Therapeutic Utility Of A Smarca2 Degrader In Smarca4 Mutant Cancer, Sasikumar Kotagiri, Nicholas Blazanin, Yuanxin Xi, Yanyan Han, Md Qudratullah, Xiaobing Liang, Yawen Wang, Poonam Pandey, Hira Mazhar, Truong Nguyen Lam, Anand Kamal Singh, Jing Wang, Yonathan Lissanu

Faculty, Staff and Student Publications

Genomic studies have identified frequent mutations in subunits of the SWI/SNF (switch/sucrose non-fermenting) chromatin remodeling complex including SMARCA4 and ARID1A in non-small cell lung cancer (NSCLC). Genetic evidence indicates that the paralog SMARCA2 is synthetic lethal to SMARCA4 suggesting SMARCA2 is a valuable therapeutic target. However, the discovery of selective inhibitors of SMARCA2 has been challenging. Here, we utilized structure-activity relationship (SAR) studies to develop YD23, a potent and selective proteolysis targeting chimera (PROTAC) targeting SMARCA2. Mechanistically, we show that SMARCA2 degradation induces reprogramming of the enhancer landscape in SMARCA4-mutant cells with loss of chromatin accessibility at enhancers of genes …