Medicine and Health Sciences Commons^™

Serum Metabolome Profiling In Patients With Mild Cognitive Impairment Reveals Sex Differences In Lipid Metabolism, Rocio Diaz Escarcega, Vijay Kumar M J, Vasilia E Kyriakopoulos, Guadalupe J Ortiz, Aaron M Gusdon, Huihui Fan, Pedram Peesh, Maria P Blasco Conesa, Gabriela Delevati Colpo, Hilda W Ahnstedt, Lucy Couture, Stella H Kim, Miriam Hinojosa, Christine M Farrell, Sean P Marrelli, Akihiko Urayama, Bhanu P Ganesh, Paul E Schulz, Louise D Mccullough, Andrey S Tsvetkov

Faculty, Staff and Student Publications

Alzheimer's disease (AD) affects more women than men. Although women live longer than men, it is not longevity alone, but other factors, including metabolic changes, that contribute to the higher risk of AD in women. Metabolic pathways have been implicated in AD progression, but studies to date examined targeted pathways, leaving many metabolites unmeasured. Sex is often a neglected biological variable, and most metabolomic studies were not designed to investigate sex differences in metabolomic profiles. Here, we performed untargeted metabolomic profiling of sera from male and female patients with mild cognitive impairment (MCI), a common precursor to AD, and matched …

Sex Differences In Brain Iron Deposition And Microglial Ferritin In Alzheimer’S Disease, Syed Mushfiqur Rahman, Chunfeng Tan, Akiyoshi Kakita, Jose Felix Moruno-Manchon

Faculty, Staff and Student Publications

Objective

Iron is the most abundant metal in the human brain, and plays a crucial role in many biological processes. However, disruptions in brain iron metabolism can lead to iron buildup, which occurs with aging and is linked to several brain disorders, including Alzheimer's disease. Microglia, the brain's resident immune cells, have the highest capacity to store iron, which is stored intracellularly within ferritin complexes. Importantly, women are at a higher risk of developing Alzheimer's disease and experience faster disease progression compared to men.

Methods

We used postmortem brain samples from patients with Alzheimer's disease and small vessel disease patients …

Heritability And Shared Environmental Effects Of Brain Diseases In 12,040 Extended Families, Janna I R Dijkstra, Marc Hulsman, Lisa Waterink, Henne Holstege, Charlotte E Teunissen, Wouter F L Christiaansen, Bryan A De Jong, Peter Kochunov, Brian Donohue, Marissa D Zwan, Anouk Den Braber, Lisa Vermunt, Sven J Van Der Lee

Faculty, Staff and Student Publications

Brain diseases have complex patterns of genetic and environmental risk factors, and better understanding of these risks is required for more effective prevention strategies. Participants of the Dutch Brain Research Registry provided detailed information on family structure and occurrence of brain diseases. A total of 12,040 participants (73% female, aged 64.9 ± 11 years) provided information on 101,379 family members (53% female, aged 62 ± 25 years). We estimated heritability (h2) of the nine most common brain diseases using polygenic modeling in SOLAR and assessed variations in h2 through bootstrapping; Alzheimer’s disease (AD) (h2 = …

Endoneurial Immune Interplay In Peripheral Nerve Repair: Insights And Implications For Future Therapeutic Interventions, Alina Sprenger-Svačina, Martin K R Svačina, Husniye G Otlu, Tong Gao, Kazim A Sheikh, Gang Zhang

Faculty, Staff and Student Publications

The mechanisms underlying axonal injury and repair in peripheral nerves, whether due to traumatic damage or autoimmune neuropathies, are complex and not yet fully understood. Recent research indicates that an orchestrated interplay between damaged neurons, Schwann cells, and especially endoneurial immune cells such as macrophages or T cells is crucial to achieve satisfactory nerve recovery. Following axonal injury, degenerating axons and reactive Schwann cells release chemoattractants and cytokines that recruit immune cells into the endoneurium. Among them, macrophages play a pivotal role by clearing axonal and myelin debris and subsequently creating a pro-regenerative microenvironment that supports axonal outgrowth. There is …

Leveraging Snomed Ct For Patient Cohort Identification Over Heterogeneous Ehr Data, Xubing Hao, Yan Huang, Licong Cui, Xiaojin Li

Faculty, Staff and Student Publications

SNOMED CT is extensively employed to standardize data across diverse patient datasets and support cohort identification, with studies revealing its benefits and challenges. In this work, we developed a SNOMED CT-driven cohort query system over a heterogeneous Optum® de-identified COVID-19 Electronic Health Record dataset leveraging concept mappings between ICD-9-CM/ICD-10-CM and SNOMED CT. We evaluated the benefits and challenges of using SNOMED CT to perform cohort queries based on both query code sets and actual patients retrieved from the database, leveraging the original ICD-9-CM and ICD-10-CM as baselines. Manual review of 80 random cases revealed 65 cases containing 148 true positive …

Leveraging Gpt-4o For Automated Extraction Of Neural Projections From Scientific Literature, Rashmie Abeysinghe, Gorbachev Jowah, Licong Cui, Samden D Lhatoo, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Sudden Unexpected Death in Epilepsy (SUDEP) is a major cause of death for epilepsy patients having uncontrolled seizures. Understanding the complex neural circuits within the central nervous system is crucial for understanding the mechanisms underlying cardiorespiratory regulation, particularly in the context of SUDEP. This study explores the potential of GPT-4o, a cutting-edge language model, to automate the extraction of neural projections from scientific literature. We developed prompts to extract neuroscientific structures, extract projections, and perform synonym harmonization. Applying the approach to four neuroscientific articles, the method extracted 205 projections. A random sample of 100 projections identified was handed over to …

Identifying Acute Myeloid Leukemia Subtypes Based On Pathway Enrichment, Ling Zhong, Jiangti Luo, Junze Dong, Xiang Yang, Xiaosheng Wang

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and the second most common in children. Despite the introduction of targeted therapies, AML survival rates have shown limited improvement, particularly among older patients. This study explored personalized treatment strategies for AML by proposing a novel subtyping method. Through unsupervised clustering based on the enrichment scores of 14 pathways related to metabolism, immunity, DNA repair, and oncogenic signaling, we identified three AML subtypes: DNA repair (DR), immune-enriched (ImE), and immune-deprived (ImD), consistent in four independent datasets. DR is marked by high expression of DNA repair and …

Gene Expression Changes In Human Cerebral Arteries Following Hemoglobin Exposure: Implications For Vascular Responses In Sah, Chathathayil M Shafeeque, Arif O Harmanci, Sithara Thomas, Ari C Dienel, Devin W Mcbride, Kumar T Peeyush, Spiros L Blackburn

Faculty, Staff and Student Publications

Subarachnoid hemorrhage (SAH), characterized by the presence of hemoglobin (Hb) in the subarachnoid space, significantly impacts cerebral vessels, leading to various pathological outcomes. The toxicity of cell-free Hb released from erythrocytes and its metabolites after SAH causes vasoconstriction and neuronal damage, and correlates with delayed ischemic neurological deficits (DIND). While animal models have provided substantial and invaluable data in the research of aneurysmal SAH, the specific effects of subarachnoid blood on cerebral arteries remain greatly understudied. Here, we describe the changes in the genetic profile of human cerebral arteries exposed to free Hb for 48 h. We performed an ex …

Automatic Summarization Of Doctor-Patient Encounter Dialogues Using Large Language Model Through Prompt Tuning, Mengxian Lyu, Cheng Peng, Xiaohan Li, Patrick Balian, Jiang Bian, Yonghui Wu

Faculty, Staff and Student Publications

Automatic text summarization (ATS) is an emerging technology to assist clinicians in providing continuous and coordinated care. This study presents an approach to summarize doctor-patient dialogues using generative large language models (LLMs). We developed prompt-tuning algorithms to instruct generative LLMs to summarize clinical text. We examined the prompt-tuning strategies, the size of soft prompts, and the few-short learning ability of GatorTronGPT, a generative clinical LLM developed using 277 billion clinical and general English words with up to 20 billion parameters. We compared GatorTronGPT with a previous solution based on fine-tuning of a widely used T5 model, using a clinical benchmark …

Designing A Narrative-Based Video Game For Adolescents Coping With A Parent's Cancer, Sophia Hamilton, Xubing Hao, Sharon Andrews, Eveyln Roldan, Carlos Martinez, Jane Hamilton, Muhammad Tuan Amith, Licong Cui

Faculty, Staff and Student Publications

We developed the narrative video game Sophia that immerses users in the story of a 13-year-old girl during her father's 18-month battle with glioblastoma and her journey toward resilience during her high school years following his passing. The game is designed to engage adolescents coping with parental cancer in multiple gameplay modes and levels, the character, and the outcome of the story as a way to build connections and explore the themes of illness, dying, bereavement, and resilience. The scenes at each level correspond to the stages of glioblastoma illness as well as the teenage milestones she passes through without …

Recombinant Factor Viia: New Insights Into The Mechanism Of Action Through Product Innovation, Miguel A Escobar, Maureane Hoffman, Giancarlo Castaman, Cedric Hermans, Johnny Mahlangu, Johannes Oldenburg, Charles L Percy, Mark T Reding, Amy D Shapiro, Steven W Pipe

Faculty, Staff and Student Publications

Management of bleeding in persons with hemophilia and inhibitors involves treatment with bypassing agents, including recombinant activated factor VII (rFVIIa). Two rFVIIa products are commercially approved for use in the United States and the European Union. Eptacog alfa and eptacog beta share the same amino acid sequence but differ in posttranslational modifications. Although rFVIIa has been used to manage bleeding in persons with hemophilia and inhibitors for over 30 years, its mechanisms of action is still being studied. In vitro and in vivo studies have suggested that rFVIIa could promote hemostasis by (1) increasing tissue factor-dependent activation of factor (F)X …

Enhancing Medication Storage Protocols For Safety Optimization In Cardiac Care Unit Inpatients, Baothu Nguyen

Doctor of Nursing Practice Final Project Abstract

Purpose: This quality improvement project aimed to enhance medication security in the cardiac care unit by implementing a standardized storage protocol to reduce unsecured medications by 20% by December 6, 2024, following a 93-day implementation period. Additionally, the project sought to achieve 100% staff competency in the protocol by September 30, 2024.

Background: Unsecured medications pose significant patient safety risks, including unauthorized access, incorrect administration, and treatment delays. This project aligned with the Patient-Centered Caritas Model and addressed compliance deficiencies identified by the Joint Commission and the hospital’s quality control team.

Methodology: A Plan-Do-Study-Act (PDSA) framework guided the project, integrating …

Improving Pituitary Lab Evaluation Following Radiation Therapy For Sinonasal/Nasopharyngeal Malignancies, Brandon M. Mcanulty, Msn, Aprn, Agacnp-Bc, Rnfa

Doctor of Nursing Practice Final Project Abstract

Purpose: The purpose of this QI project was to create a standardized order set aiming to increase consistency in lab work completion for improved monitoring of pituitary dysfunction in patients diagnosed with sinonasal and nasopharyngeal malignancies. Background: Radiation therapy is important in the treatment plan for this population. The hypothalamic-pituitary axis is frequently included within the radiation field, contributing to radiation induced pituitary dysfunction. There is no established order set for outpatient pituitary lab monitoring at the organization. Methods: Established order sets were modified to include pituitary labs to create a centralized ordering workflow among providers from all three departments …

Iimproving Discharges Within The Monitored Pod Units Of A Regional Health Center In Bryan, Tx, Paul R. Russell Iii

Doctor of Nursing Practice Final Project Abstract

IMPROVING DISCHARGE RATES WITHIN THE MONITORED POD UNITS OF A REGIONAL HEALTH CENTER IN BRYAN, TX

Purpose

The purpose of this scholarly project was to improve discharges by 11:00 a.m. within the Monitored Pod Units located in a regional hospital in Bryan, Texas.

Background

The current discharge rate by 1100 for the monitored pod units at the regional health center was below the health system goal of 50%. The impacts of delayed discharges are broad and can be seen throughout the regional health center. Delayed discharges have a direct effect on staff satisfaction, patient satisfaction, and decreased revenue.

Methodology

This …

Reducing Hospital-Acquired Pressure Injuries: A Quality Improvement Project Implementing A Visual Reminder System In The Intensive Care Unit, Henry H. Remschel Iii

Doctor of Nursing Practice Final Project Abstract

Purpose

This quality improvement (QI) project aimed to reduce hospital-acquired pressure injuries (HAPIs) by 10% in an intensive care unit through the implementation of a skin risk assessment form and a visual reminder system.

Background

Hospital-acquired pressure injuries negatively impact patient outcomes and can increase costs associated with a hospital stay. Studies have shown that visual reminders can improve nursing intervention compliance and correlate with improved patient outcomes.

Methodology

The project implemented a skin-risk assessment form to identify patients at risk for developing pressure injuries during their hospital stay. For high-risk patients, a “High Skin Risk” magnet was placed outside …

Tissue Kallikrein 1 Cleaves Complement Factor C3 And Activates The Alternative Complement Pathway, Sarah E. Sartain, Andrew Yee, Paula Jacobi

Research Data

Hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), characterized by microvascular endothelial damage and severe renal injury, negatively affects HSCT survivorship with high mortality and long-term renal morbidity. After HSCT, innate immunity and inflammation are often dysregulated. The alternative complement pathway (AP) of the innate immune system is overactivated in HSCT-TMA, but the mechanisms of its initiation are poorly described. Complement component C3 of the AP can be cleaved by proteases outside of the AP. Because mRNA expression of tissue kallikrein 1 (KLK1), an inflammatory serine protease that produces kinins, has been found to be markedly elevated in the renal endothelium …

Additional Evidence From A Case Report Supports A Novel Hypothesis On The Association Between Complex Regional Pain Syndrome And Lymphedema, M Mark Melin, John C Rasmussen, Melissa B Aldrich, Ron J Karni, Caroline E Fife, Kristen A Eckert

The Brown Foundation: Institute of Molecular Medicine

A previous report of 4 heterogeneous cases demonstrated that automated manual lymphatic drainage therapy (AMLDT), administered by a novel, pneumatic mat of 16 pressurized air channels that inflate and deflate sequentially to mimic the stretch and release action of manual lymphatic drainage therapy (MLD), altered lymphatic contractility and relieved pain. Near-infrared fluorescence imaging (NIRF-LI) was used 1 h before AMLDT, during 1 h of AMDLT, and 30-60 min after treatment to obtain images that could be used to determine lymphatic contractility, as measured by pulsing frequency over a given timeframe. Herein, a case of type 2 complex regional pain syndrome …

Editorial: Advances In Pharmacotherapy For Alcohol Use Disorder: From Mechanisms To Clinical Interventions, Regina A Mangieri, Sunil Sirohi, Ezequiel Marron Fernandez De Velasco, Seungwoo Kang

The Brown Foundation: Institute of Molecular Medicine

No abstract provided.

Microglial Trem2 Promotes Phagocytic Clearance Of Damaged Neurons After Status Epilepticus, Dale B Bosco, Vaclav Kremen, Koichiro Haruwaka, Shunyi Zhao, Lingxiao Wang, Blake A Ebner, Jiaying Zheng, Manling Xie, Aastha Dheer, Jadyn F Perry, Abhijeet Barath, Aivi T Nguyen, Gregory A Worrell, Long-Jun Wu

The Brown Foundation: Institute of Molecular Medicine

In the central nervous system, triggering receptor expressed on myeloid cells 2 (TREM2) is exclusively expressed by microglia and is critical for microglial proliferation, migration, and phagocytosis. Microglial TREM2 plays an important role in neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis. However, little is known about how TREM2 affects microglial function within epileptogenesis. To investigate this, we utilized male TREM2 knockout (KO) mice within the intra-amygdala kainic acid seizure model. Electroencephalographic analysis, immunocytochemistry, and RNA sequencing revealed that TREM2 deficiency significantly promoted seizure-induced pathology. We found that TREM2 KO increased both the severity of acute status epilepticus …

Depletion Of Adipose Stroma-Like Cancer-Associated Fibroblasts Potentiates Pancreatic Cancer Immunotherapy, Joseph Rupert, Alexes Daquinag, Yongmei Yu, Yulin Dai, Zhongming Zhao, Mikhail G Kolonin

Faculty, Staff and Student Publications

This study shows that populations of CAFs have distinct effects on pancreatic cancer progression and shows that depletion of CAFs expressing adipose markers potentiates tumor/metastasis suppression effects of immune checkpoint blockade.

Tagraxofusp Maintenance Post-Hematopoietic Stem Cell Transplantation Provides Long-Term Survival And Manageable Safety For A Patient With Blastic Plasmacytoid Dendritic Cell Neoplasm, Qaiser Bashir, Marina Konopleva, Glorette Abueg, Jeremy Ramdial, Chitra Hosing, Samer A Srour, Amin Alousi, Uday R Popat, Yago Nieto, Gheath Alatrash, Richard E Champlin, Elizabeth J Shpall, Muzaffar Qazilbash, Naveen Pemmaraju

Faculty, Staff and Student Publications

Presented here is the case of a 68-year-old woman with blastic plasmacytoid dendritic cell neoplasm (BPDCN) treated with tagraxofusp (TAG) maintenance therapy post-allogeneic hematopoietic stem cell transplantation (allo-HCT). Prior to allo-HCT, the patient was treated with hydroxyurea and mini-CVD (cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate (Methotrexate) and cytarabine) + venetoclax + TAG for 5 cycles, which induced morphologic complete remission with minimal residual disease. After allo-HCT, the patient had persistent cytogenic abnormalities 45,XX,der(7)add(7)(p13)del(7)(q11.2q22)add(7)(q32),add(12)(p13),-15,del(16)(q23),-17,+22,+2mar[1]/46,XX[19], and was then treated with TAG maintenance therapy at 9 mg/kg on a 28-day cycle for 16 cycles. At mid-treatment (cycle 6 of 16 cycles of …

Co-Morbid Indomethacin-Responsive Headaches In A Woman In Her Late 60s With Paroxysmal Hemicrania And Hypnic Headache: A Case Report, Ashlyn Brown, Randolph W Evans, Claudia Carrizo, Mark Burish

Faculty, Staff and Student Publications

Paroxysmal hemicrania (PH) and hypnic headache (HH) are rare indomethacin-responsive headache syndromes. This case report details the new onset of both disorders in a woman in her late 60s. One headache type presented as severe pain centered on the right eyebrow, lasting 30 minutes, occurring more than 8 times daily, and associated with ipsilateral lacrimation and rhinorrhea. The second type was a right frontal severe pain, with onset at 4 a.m., occurring only during sleep, lasting 30 minutes, and with no associated factors. The patient's response to indomethacin for both headache types was confirmed through an unblinded ABAB study design: …

A Bayesian Deep Segmentation Framework For Glioblastoma Tumor Segmentation Using Follow-Up Mris, Tanjida Kabir, Kang-Lin Hsieh, Luis Nunez, Yu-Chun Hsu, Juan C Rodriguez Quintero, Octavio Arevalo, Kangyi Zhao, Jay-Jiguang Zhu, Roy F Riascos, Mahboubeh Madadi, Xiaoqian Jiang, Shayan Shams

Faculty, Staff and Student Publications

Background: Glioblastoma (GBM) is the most common malignant brain tumor with an abysmal prognosis. Since complete tumor cell removal is impossible due to the infiltrative nature of GBM, accurate measurement is paramount for GBM assessment. Preoperative magnetic resonance images (MRIs) are crucial for initial diagnosis and surgical planning, while follow-up MRIs are vital for evaluating treatment response. The structural changes in the brain caused by surgical and therapeutic measures create significant differences between preoperative and follow-up MRIs. In clinical research, advanced deep learning models trained on preoperative MRIs are often applied to assess follow-up scans, but their effectiveness in this …

Examining Educational And Career Transition Points Among A Diverse, Virtual Mentoring Network, Erika L Thompson, Toufeeq Ahmed Syed, Zainab Latif, Katie Stinson, Damaris Javier, Gabrielle Saleh, Jamboor K Vishwanatha

Faculty, Staff and Student Publications

Given the differences in trajectory for under-represented minorities in biomedical careers, we sought to explore how a virtual mentoring program, the National Research Mentoring Network (NRMN), and its platform (MyNRMN), may facilitate transitions in the science, technology, engineering, mathematics, and medicine (STEMM) pipeline. The purpose of this study was to describe how the size of an MyNRMN member’s mentoring network and level of engagement correlate with academic and career transitions. We examined MyNRMN platform user data from March 2020 to May 2021 (n = 2993). Logistic regression estimated the odds of a career or academic transition related to NRMN …

Key Considerations For Combination Therapy In Alzheimer’S Clinical Trials: Perspectives From An Expert Advisory Board Convened By The Alzheimer’S Drug Discovery Foundation, Jeffrey Cummings, Michael Gold, Mark Mintun, Michael Irizarry, Andrew Von Eschenbach, Suzanne Hendrix, Donald Berry, Cristina Sampaio, Kaycee Sink, Jaren Landen, Miia Kivipelto, Michael Grundman, Steven E Arnold, Allan Green, Katherine Partrick, Laura Nisenbaum, Aaron Burstein, Howard Fillit

Faculty, Staff and Student Publications

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas. Experts agreed on the need to prioritize a combination therapy approach that encompasses a wide range of targets associated with aging and the underlying biology of Alzheimer's disease. Progress …

How Gps Communicate The Urgent Suspected Cancer Referral Pathway To Patients: A Qualitative Study Of Gp-Patient Consultations, Jessica Russell, Laura Boswell, Athena Ip, Jenny Harris, Hardeep Singh, Ashley Nd Meyer, Traber D Giardina, Afsana Bhuiya, Katriina L Whitaker, Georgia B Black

Faculty, Staff and Students Publications

Background: The UK National Institute for Health and Care (NICE) recommends that GPs inform patients referred onto the urgent suspected cancer (USC) pathway about what to expect from the service. However, there is a lack of evidence on patient experience and information needs at the point of referral. It is a challenge for GPs to communicate the reasons for referral and provide reassurance.

Aim: To examine how GPs communicate a potential cancer diagnosis and USC referral in practice.

Design & setting: This is a secondary analysis of a dataset of 23 audio-recorded GP-patient consultations, selected from a larger dataset of …

Early Versus Late Initiation Of Dialysis In Ckd Stage 5: Time For A Consensus, Emaad M Abdel-Rahman, Irtiza Hasan, Abdallah S Abdelrazeq, Ali Rawabdeh, Mei Liu, Nasrollah Ghahramani, David Sheikh-Hamad, Mariana Murea, Pradeep Kadambi, T Alp Ikizler, Alaa S Awad

Faculty, Staff and Students Publications

Chronic kidney disease (CKD), a major global public health problem, emerged as one of the leading causes of death, affecting over 800 million individuals worldwide, with significant burden to patients and their caregivers, and may lead to end-stage kidney disease (ESKD). The decision on optimal initiation of chronic dialysis is a common problem faced by nephrologists, patients, and caregivers due to lack of adequate data. Determining the ideal time to initiate maintenance dialysis for individuals struggling with ESKD has remained a puzzle. Currently, there is no consensus among guidelines as to the best time to initiate dialysis. Discrepancies in guidelines …

Thromboelastography Versus Thromboelastometry For Unfractionated Heparin Monitoring In Adult Patients On Extracorporeal Membrane Oxygenation, Ellen B Yin, Arthur W Bracey, Subhasis Chatterjee

Faculty, Staff and Students Publications

Background: Monitoring the anticoagulant effect of unfractionated heparin (UFH) in extracorporeal membrane oxygenation (ECMO) patients is complex but critically important to balance the risks of treatment related bleeding and circuit thrombosis. While guidelines recommend using more than one method to monitor UFH activity, the use of thromboelastometry (ROTEM) to monitor UFH in ECMO patients has not been investigated in detail.

Methods: This is an observational, single-center retrospective study looking at adult ECMO patients on UFH that had ROTEM and thromboelastography (TEG) tests obtained concurrently. A total of 20 samples were obtained from nine patients during the study period, …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Transposable Element Activity Captures Human Pluripotent Cell States, Florencia Levin-Ferreyra, Srikanth Kodali, Yingzhi Cui, Alison R S Pashos, Patrizia Pessina, Justin Brumbaugh, Bruno Di Stefano

Faculty, Staff and Students Publications

Human pluripotent stem cells (hPSCs) exist in multiple, transcriptionally distinct states and serve as powerful models for studying human development. Despite their significance, the molecular determinants and pathways governing these pluripotent states remain incompletely understood. Here, we demonstrate that transposable elements act as sensitive indicators of distinct pluripotent cell states. We engineered hPSCs with fluorescent reporters to capture the temporal expression dynamics of two state-specific transposable elements, LTR5_Hs, and MER51B. This dual reporter system enables real-time monitoring and isolation of stem cells transitioning from naïve to primed pluripotency and further towards differentiation, serving as a more accurate readout of pluripotency …