Digital Commons Network^™

The Role Of Regulatory T Cells In Ischemic Heart Disease Patients, Duha Alaa Hassan, Hayfaa Mahmood Fahad, Saad Fadhel Nassar

Al-Nisour Journal for Medical Sciences

Background: Regulatory T cells (Tregs) represent 5–10% of the total T cell population and are known as potent suppressors of the immune system. They are crucial for managing immune activation, ensuring peripheral tolerance, and supporting tissue repair and overall homeostasis. These cells are characterized by the expression of specific biomarkers, including CD4+, FOXP3+, and CD25+. While CD4 and CD25 were initially used for their identification, the discovery of CD25 on other T cell types led to a more precise evaluation of Tregs through the assessment of the intracellular Foxp3 transcription factor.

Objective: The primary goal of this study was to …

Vaccine Value Profile For Schistosomiasis, Gavin Yamey, Kaci Kennedy Mcdade, Roy M Anderson, Sarah M Bartsch, Maria Elena Bottazzi, David Diemert, Peter J Hotez, Bruce Y Lee, Donald Mcmanus, Adebayo J Molehin, Meta Roestenberg, David Rollinson, Afzal A Siddiqui, Miriam Tendler, Joanne P Webster, Hong You, Raphaël M Zellweger, Caroline Marshall

Faculty, Staff and Students Publications

Schistosomiasis is caused by parasitic flatworms (Schistosoma). The disease in humans can be caused by seven different species of Schistosoma: S. mansoni, S. japonicum, S. haematobium, S. malayensis, S. mekongi, S. guineensis and S. intercalatum, as well as by hybrids between species, including livestock schistosome species. People are infected when exposed to infested water and the parasite larvae penetrate the skin. Poor and rural communities are typically the most affected, and the general population who lives in affected areas and is exposed to contaminated water is at risk. Areas with poor access to safe water and adequate sanitation are also …

All-Optical Voltage Interrogation For Probing Synaptic Plasticity In Vivo, Jacques Carolan, Michelle A Land, Xiaoyu Lu, Maxime Beau, Dimitar Kostadinov, François St-Pierre, Beverley A Clark, Michael Häusser

Faculty, Staff and Students Publications

Measuring synaptic efficacy and defining the rules for induction of synaptic plasticity at identified connections in the mammalian brain is essential for understanding how synapses contribute to learning and memory. This requires new approaches to selectively evoke presynaptic activity and measure postsynaptic responses with high spatiotemporal resolution and high sensitivity over long periods in vivo. Here we develop an all-optical approach to probe synaptic plasticity at identified cerebellar synapses in awake, behaving mice. We developed and applied JEDI-2Psub, a genetically encoded voltage indicator with increased sensitivity around resting membrane potentials, to record subthreshold and suprathreshold activity in Purkinje cell (PC) …

Genome-Wide Analysis Of Dna Methylation Signatures Linking Prenatal Exposure To The Chinese Great Famine And Blood Lipids In Late Adulthood: The Genomic Research Of The Chinese Famine (Grecf) Study, Huan Wang, Luqi Shen, Tingting Liu, Ruiyuan Zhang, Zhenghe Wang, Jingkai Wei, Ye Shen, Jinzhen Guo, Toni Miles, Changwei Li, Zhiyong Zou

Faculty, Staff and Student Publications

Background/objectives: Prenatal exposure to famine can lead to lasting health effects through changes in DNA methylation. This study aims to evaluate the impact of prenatal exposure to the Chinses Great Famine (1959-1961) on human epigenome and the subsequent influence on blood lipids.

Methods: We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and prenatal exposure to the Chinese Great Famine as well as blood lipids among eight participants exposed to famine and eight sex-matched participants (born ≤ 3 years after the famine). Genome-wide DNA methylation sites were profiled using the Illumina EPIC BeadChip, which covers 850K methylation …

A Needed Nomenclature For Nucleosomes, Michael-Christopher Keogh, Genevieve Almouzni, Andrew J Andrews, Karim-Jean Armache, Cheryl H Arrowsmith, Sung Hee Baek, Mark T Bedford, Emily Bernstein, Jacques Côté, Yael David, John M Denu, Beat Fierz, Benjamin A Garcia, Karen C Glass, Or Gozani, Kristian Helin, Steven Henikoff, Ole N Jensen, Steven Z Josefowicz, Neil L Kelleher, Tatiana G Kutateladze, Herbert H Lindner, Chao Lu, Karolin Luger, Parag Mallick, Catherine A Musselman, Tom W Muir, Ljiljana Paša-Tolić, Robert Schneider, Xiaobing Shi, Yang Shi, Simone Sidoli, Lloyd M Smith, Jessica K Tyler, Cynthia Wolberger, Jerry L Workman, Brian D Strahl, Nicolas L Young

Faculty, Staff and Student Publications

Histone post-translational modifications (PTMs) are crucial to eukaryotic genome regulation, with a range of reported functions and mechanisms of action. Though often studied individually, it has long been recognized that the modifications function by combinatorial synergy or antagonism. Interplay may involve PTMs on the same histone, within the same nucleosome (containing a histone octamer), or between nucleosomes in higher-order chromatin. Given this, the field must distinguish ever greater complexity, and the context in which it is studied, with brevity and precision. The proteoform was introduced to define individual forms of a protein by sequence and PTMs, followed by the nucleoform …

Methylation Of The Dat1 Dopamine Transporter Gene In Combat Sport Athletes: Associations With Impulsivity And Reward Sensitivity, Milena Lachowicz, Remigiusz Recław, Aleksandra Suchanecka, Krzysztof Chmielowiec, Elżbieta Grzywacz, Jolanta Chmielowiec, Kinga Łosińska, Anna Grzywacz

Baltic Journal of Health and Physical Activity

Epigenetic mechanisms, such as DNA methylation, modulate behavioral traits, including impulsivity and reward sensitivity. The dopamine transporter gene (DAT1) plays a key role in dopaminergic function and is associated with self-regulation, attention, and the trait of addiction. This study summarized the DAT1 methylation status in patients practicing combat sports and its association with impulsivity, ADHD symptoms, and consequence sensitivity. One hundred control subjects were recruited using the Barratt Impulsivity Scale (BIS), the ADHD scale, and the Opportunity Response Scale. DAT1 methylation was measured using the bisulfite ionization method. A correlation analysis was performed with the comparison group. Athletes …

Neuronal Activity-Dependent Gene Dysregulation In C9orf72 I3neuronal Models Of Als/Ftd Pathogenesis, Layla T. Ghaffari, Emily A. Welebob, Sarah E. Bond Newton, Ashley V. Boehringer, Kelly L. Cyliax, Piera Pasinelli, Davide Trotti, Aaron R. Haeusler

Farber Institute for Neuroscience Faculty Papers

The GGGGCC nucleotide repeat expansion (NRE) mutation in the C9ORF72 (C9) gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Neuronal activity plays an essential role in shaping biological processes within both healthy and neurodegenerative disease scenarios. Here, we show that at baseline conditions, C9-NRE-induced pluripotent stem cell-cortical neurons display aberrations in several pathways, including synaptic signaling and transcriptional machinery, potentially priming diseased neurons for an altered response to neuronal stimulation. Indeed, exposure to two pathophysiologically relevant stimulation modes, prolonged membrane depolarization or a blockade of K⁺ channels, followed by RNA sequencing, induces …

Escape Of Kdm6a From X Chromosome Is Detrimental To Ischemic Brains Via Irf5 Signaling, Conelius Ngwa, Afzal Misrani, Kanaka Valli Manyam, Yan Xu, Shaohua Qi, Romana Sharmeen, Juneyoung Lee, Long-Jun Wu, Louise Mccullough, Fudong Liu

The Brown Foundation: Institute of Molecular Medicine

The role of chromatin biology and epigenetics in disease progression is gaining increasing recognition. Genes that escape X chromosome inactivation (XCI) can impact neuroinflammation through epigenetic mechanisms. Our previous study has suggested that the X escapee genes Kdm6a and Kdm5c are involved in microglial activation after stroke in aged mice. However, the underlying mechanisms remain unclear. We hypothesized that Kdm6a/5c demethylate H3K27Me3/H3K4Me3 in microglia, respectively, and mediate the transcription of interferon regulatory factor 5 (IRF5) and IRF4, leading to microglial pro-inflammatory responses and exacerbated stroke injury. Aged (17–20 months) Kdm6a/5c microglial conditional knockout (CKO) female mice (one allele of the …

Use Of Modified Z-Domain Peptides To Specifically Label The Constant Region Of Immunoglobulin G And Vegf, Madeline Allen

Department of Chemistry: Dissertations, Theses, and Student Research

Antibodies are increasingly being used in medicinal therapies due to their ability to specifically bind to a target antigen. This fundamental behavior of antibodies has been used as a key component in drug development to address common problems with traditional drug molecules such as off-targeting, fast drug clearance, and low efficacy. This thesis provides some background into how antibodies can be used as potential treatments for a few diseases. Chapter 1 begins with an overview of the human immune system, and the role antibodies play within it. Then, the variety of ways in which antibodies can be used as medicinal …

Hydrogen Sulfide Inhibits Recruitment Of Monocyte-Derived Tumor Associated Macrophages In Glioblastoma By Downregulating Cxcl12, Joseph Camarano, Morgan Roque, Gabrielle Gahn, Stephen Garrett Whipple, Danielle Terrell, Charles Ronkon, Jamie Toms, Anthony Sin, Bharat Guthikonda, Khatri Latha, Yuhui Yang, Xinggui Shen, Christopher G Kevil, Ganesh Rao, Sungho Lee

Faculty, Staff and Students Publications

Tumor associated macrophages (TAMs) directly contribute to the dismal prognosis of glioblastoma by preventing anti-tumor immunity and promoting tumor invasion and angiogenesis. Inhibiting TAM infiltration is a potential therapeutic strategy in glioblastoma, with several chemokine antagonists in early clinical development. Hydrogen sulfide, a gasotransmitter that regulates microglial accumulation in a wide range of CNS diseases, may be a novel therapeutic target to prevent TAM recruitment in glioblastoma. In this study, hydrogen sulfide concentrations were directly measured from 14 isocitrate dehydrogenase (IDH)-wildtype glioblastoma surgical samples and compared against overall survival as well as expression of TAM markers and chemokines. Effects of …

All-Cause And Cause-Specific Mortality Among Patients With Narcolepsy., Chih-Wei Hsu, Yen-Shan Yang, Yang-Chieh Brian Chen, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Importance: Narcolepsy is a sleep disorder potentially affecting mortality, yet evidence on this association remains sparse.

Objective: To examine whether narcolepsy is associated with an increased risk of all-cause and cause-specific mortality.

Design, setting, and participants: This retrospective cohort study used data from the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2021, with patients followed up until death or December 31, 2022. Patients were aged 6 years or older with 2 or more narcolepsy diagnoses from psychiatrists or neurologists. Controls were selected from the NHIRD as a population-based sample. Controls without narcolepsy were matched in a 1:4 …

The Science Of Sound: Studying The Cognitive, Emotional, And Physiological Effects Of Frequency, Genre, And Music, Jett Yarborough

Senior Honors Theses

Music influences emotion, physiology, and cognition, yet little is known about how the frequency it is tuned to affects these influences. Prior research has shown that music tuned to 432 Hz can reduce stress, lower blood pressure, and improve sleep. My colleagues and I conducted two studies to investigate this. Our research found that music tuned to 432 Hz promotes a significant increase in memory retention and induces a state of focus and relaxation. These results suggest that shifting from the standard tuning frequency of 440 Hz to 432 Hz could have a profoundly positive impact on our daily lives. …

Slb-Mssim: A Spectral Library-Based Multiplex Segmented Sim Platform For Single-Cell Proteomic Analysis, Lakmini Senavirathna, Cheng Ma, Van-An Duong, Hong-Yuan Tsai, Ru Chen, Sheng Pan

The Brown Foundation: Institute of Molecular Medicine

Mass spectrometry (MS)-based single-cell proteomics, while highly challenging, offers unique potential for a wide range of applications to interrogate cellular heterogeneity, trajectories, and phenotypes at a functional level. We report here the development of the spectral library-based multiplex segmented selected ion monitoring (SLB-msSIM) method, a conceptually unique approach with significantly enhanced sensitivity and robustness for single-cell analysis. The single-cell MS data is acquired by a multiplex segmented selected ion monitoring (msSIM) technique, which sequentially applies multiple isolation cycles with the quadrupole using a wide isolation window in each cycle to accumulate and store precursor ions in the C-trap for a …

Investigating Machine Learning Algorithms To Classify Label-Free Images Of Pancreatic Neuroendocrine Neoplasms, Noelle Daigle, Shuyuan Guan, Suzann Duan, Thomas G Knapp, Eung-Joo Lee, Ali Azhdarinia, Sukhen C Ghosh, Solmaz Aghaamiri, Servando Hernandez Vargas, Naruhiko Ikoma, Jeannelyn Estrella, Martin J Schnermann, Tobias Else, Michelle Kang Kim, Juanita L Merchant, Travis W Sawyer

The Brown Foundation: Institute of Molecular Medicine

Significance: Pancreatic neuroendocrine neoplasms (PNENs) are an uncommon cancer whose incidence rate has increased dramatically in recent years. Surgery is the only potentially curative treatment, which relies on both preoperative tumor localization and postoperative margin definition using histopathological examination for decision making. If pathology could be automated, valuable time and resources could be saved.

Aim: In this study, we investigate the ability of machine learning (ML) with handcrafted features, as well as deep learning, to classify label-free microscopy images of PNENs as a first step toward automated pathology of such tumors.

Approach: Patient samples of two different preparation types were …

Introducing Patient-Centered Outcomes To Preceptors In Caate-Approved Athletic Training Programs, K. Judge

Clinical Practice in Athletic Training

The 2020 standards set by the Commission on Accreditation of Athletic Training Education (CAATE) now require the incorporation of the International Classification of Function and Patient-Centered Outcomes into professional practice. These standards can be introduced initially through simulation, but to develop a competent and culturally aware professional, outcome measures should be completed during clinical experiences under the guidance of approved preceptors. As this is a relatively new standard, many preceptors did not receive this as part of their education and may be uncomfortable integrating outcomes into their practice. This lack of integration can negatively affect the learning opportunities of athletic …

Incorporating Balance Training Into Ankle Sprain Injury Prevention Programs: An Evidence-To-Practice Review, David Tomchuk, Jacob Meyer, Kyle Schneider, Ben Fox

Clinical Practice in Athletic Training

Ankle sprains are among the most common injuries in sports and non-sporting activities. For patients, ankle sprains can result in multiple short and long-term hardships, such as financial burdens of evaluation and treatment, absenteeism from sport and physical activity, and diminished ankle and lower extremity function. However, athletic trainers and other stakeholders are also impacted by administrative and time burdens in caring for ankle sprains and how ankle sprains affect team dynamics and performance. The 2022 guiding systematic review evaluated the effectiveness of incorporating preventive balance training exercises on the incidence of ankle sprains in soccer athletes. The search performed …

Psychological And Psychosocial Effects Of Contemplative Practices In The Athletic Population: A Systematic Review, Victoria Baker, Emily Duckett, Alison Gardiner-Shires, Lindsey Keenan

Clinical Practice in Athletic Training

Mental health concerns in athletes are becoming a primary focus for institutions, companies, coaches, and more. An athlete carries an abundant load of stressors due to their lifestyle. The stressors can negatively impact an athlete by producing anxiety, depression, insomnia, and other mental health concerns. Previous studies have found a connection between the use of contemplative practices on psychological and psychosocial effects in athletes, creating an opportunity to evaluate the research of contemplative practices in the athletic population. 5, 7, 8, 13-16 A systematic review was conducted using nine electronic databases. Seven studies were included in this review, each assessing …

Use Of An Electronic Dynamometer Following Pitching To Identify Fatigue In Softball Pitchers, Bethany L. Hansberger, Peter Lisman

Clinical Practice in Athletic Training

This study used a case-series design to collect in-game fatigue measures for collegiate softball pitchers immediately after pitching during the competitive season. Five softball pitchers (age = 19.8 ± 1.5 years; height = 169.9±6.1 cm; body mass = 79.1±22.6 kg) from one Division I program were recruited. Isometric internal and external rotation, scaption, and grip strength measures were collected using an electronic dynamometer at the beginning and conclusion of the fall non-traditional season, and at the beginning of preseason in January. Strength measures were also obtained during the competitive season at the conclusion of pitching in a game and compared …

Concurrent Acl And Medial/Lateral Meniscal Repair In A Collegiate Soccer Player: Disablement Model Case Study, Rebecca L. Perry, Angelica Alicea, Jeanette Welch, Carl White, Emily E. Hildebrand, Peter Lisman

Clinical Practice in Athletic Training

This case examines a 19-year-old female Division I collegiate soccer player who underwent anterior cruciate ligament (ACL) reconstruction with medial and lateral meniscal repairs. Though meniscal tears often occur in conjunction with ACL injury, incidence of concurrent medial and lateral tears with presence of a displaced bucket-handle lesion is rare. This patient attempted to tackle an oncoming opponent in which contact caused forceful trunk rotation away from her planted right foot. Sideline evaluation revealed medial and posterior knee pain with active knee range of motion deficits. Further evaluation revealed apprehension and muscle guarding during Lachman’s, anterior drawer, and valgus stress …

Suturing Education For Athletic Trainers: An Evidence-To-Practice Review, Morgan K. Webb, Brett T. Heim, Allyson E. Ritchey, Kenya Moore, Zachary K. Winkelmann

Clinical Practice in Athletic Training

Teaching suturing skills to medical students is a critical component of their education. Implementing suturing into a comprehensive framework is developed from how professors teach the skill. Suturing is a required skill by the General Medical Council that all medical students must have, and how it is being introduced to new students is changing. This review aimed to summarize different educational interventions and determine the most efficient and cost-effective way to teach future suturing skills. The original systematic review included 25 articles in the final data synthesis. Fourteen studies were randomized control trials, six were quasi-experimental, and five were observational. …

Impact Of A Focused Best Practice Workshop On Athletic Trainer Confidence, Jaclyn B. Arduini, Jennifer L. Volberding, Zachary A. Murray

Clinical Practice in Athletic Training

Athletic trainers are required to be proficient in emergency management skills, without review these skills may decay creating a potentially dangerous knowledge gap. Confidence measures of emergency management skills were taken before and after a workshop to determine if they changed due to the review of material. All 11 confidence measures increased post workshop, seven significantly, including rectal temperature, hemostatic agents, external hemostatic modalities, in-line stabilization, measurement and application of a cervical collar, football and other equipment removal. ATs should aim to incorporate emergency management review into continuing education choices.

Neuromuscular Deficits Following An Isolated Pcl Tear In A Collegiate Lacrosse Player: A Case Study, Mckenna G. Witlin, Erin R. Mcmullan, Courtney M. Meyer, Amy L. Fraley

Clinical Practice in Athletic Training

This disablement model case study outlines a 21-year-old female collegiate lacrosse player attending a United States service academy who presented with a unique neuromuscular deficit following a conservative grade II PCL tear rehabilitation. Nearing the end of her rehabilitation protocol, she noticed difficulty with toe-off while running; however, she did not report to the athletic trainer due to the institution’s holiday break proximity. An unexpected transfer of care occurred when the patient returned after the holidays, and she was cleared for full participation upon return. Several days after the patient was cleared, she reported her ankle feeling “stuck.” Upon evaluation, …

Improving The Discussion Of Suicide Prevention: A Quality Improvement Project, Chelsea Reynolds, Alyssa Zeitouni, Kathryn Stephenson

Clinical Practice in Athletic Training

Suicide is currently the second leading cause of death among adolescents in the United States and the third leading cause of death in this age group worldwide.1,2 Suicide prevention is understandably a growing focus in pediatrics. Currently, at the Children’s Hospital Outpatient Clinic, that is staffed by pediatric resident physicians, suicidal ideation is screened for using a PHQ-9 screen. However, at the time this study was initiated and completed, the TEEN screen was utilized. After the screening is performed, regardless of type, it is up to the provider to address these findings in a safe and effective manner. The goal …

Predictive Gene Expression Signatures For Alzheimer's Disease Using Post-Mortem Brain Tissue, Ashley Duche, Oliver Tan, Andrius Baskys, Rachita K. Sumbria, Moom R. Roosan

Pharmacy Faculty Articles and Research

Background: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques and tau protein aggregates in the brain. These pathological features manifest in specific regions, but mechanisms rendering some areas more susceptible to early AD-related changes remain poorly understood. To address this, we developed predictive gene expression signatures to explore molecular mechanisms underlying regional vulnerability to AD pathology.

Methods: Post-mortem brain tissues from participants of the Religious Orders Study and Memory and Aging Project (ROSMAP), Mayo Clinic, and Mount Sinai Brain Bank (MSBB) were used to derive gene expression signatures from six brain regions affected at varying …

Three-Dimensional Human Mucopolysaccharidosis Iva Chondrocyte Culture Reveals Significant Impairments In The Lysosomal-Mitochondrial Crosstalk, Andrés Felipe Leal, Sampurna Saikia, Shaukat A. Khan, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disorder (LSD) caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase enzyme. MPS IVA patients suffer from skeletal dysplasia due to the abnormal function of chondrocytes. Given the interactions of lysosomes with various intracellular organelles, it is not surprising that lysosomal dysfunction can lead to improper functioning of lysosome-interacting organelles such as mitochondria. Mitochondrial alterations have been evaluated in several LSDs; nevertheless, they have not been fully addressed in MPS IVA. In this study, we assessed the mitochondrial alterations in MPS IVA chondrocytes using a three-dimensional culture approach. Our findings revealed that MPS IVA …

Examining Burnout Among Athletic Trainers Employed In The College And Secondary School Settings, Stephanie M. Singe, Dayna Liu, Alexandrya Cairns

Clinical Practice in Athletic Training

Burnout continues to be an important concern for athletic trainers working traditional employment settings. The purpose of this study was to compare the secondary school and collegiate settings in relation to burnout. Both secondary school and collegiate athletic trainers participated in a self-reported, online cross-sectional design (Qualtrics) to collect data on their experiences with burnout. Data collection occurred during the second week of October 2023 and ceased during the early weeks of November. Collegiate athletic trainers reported moderate burnout overall (54.56 ±15.89) on the CBI whereas secondary school athletic trainers reported low burnout overall (46.67 ±16.57). On the personal-related burnout …

Conservative Management Of Athletic Pubalgia In A Collegiate Beach Volleyball Athlete: A Case Study, Sydney F. Hendrick, Amy L. Fraley, Madison V. Kefferstan, Zachary K. Winkelmann

Clinical Practice in Athletic Training

A 24-year-old female collegiate beach volleyball athlete experienced sharp pain in the pubis symphysis region after turning and running to reach a ball hit over her right shoulder. The patient was unable to move her lower extremities without extreme pain and required help off the court. She was referred to the student health center, where no initial imaging was performed. Differential diagnoses included osteitis pubis, abdominal strain, and athletic pubalgia. Magnetic resonance imaging (MRI) showed a small partial sports hernia with the shearing of the aponeurotic plate. The team physician recommended conservative management. The patient requested a consultation with a …

Consensus Recommendations For Hyperpolarized [1- 13c]Pyruvate Mri Multi-Center Human Studies, Shonit Punwani, Peder E Z Larson, Christoffer Laustsen, Jan Vandermeulen, Jan Henrik Ardenkjær-Larsen, Adam W Autry, James A Bankson, Jenna Bernard, Robert Bok, Lotte Bonde Bertelsen, Jenny Che, Albert P Chen, Rafat Chowdhury, Arnaud Comment, Charles H Cunningham, Duy Dang, Ferdia A Gallagher, Adam Gaunt, Yangcan Gong, Jeremy W Gordon, Ashley Grimmer, James Grist, Esben Søvsø Szocska Hansen, Mathilde Hauge Lerche, Richard L Hesketh, Jan-Bernd Hoevener, Ching-Yi Hsieh, Kayvan R Keshari, Sebastian Kozerke, Titus Lanz, Dirk Mayer, Mary Mclean, Jae Mo Park, Jim Slater, Damian Tyler, Jean-Luc Vanderheyden, Cornelius Von Morze, Fulvio Zaccagna, Vlad Zaha, Duan Xu, Daniel Vigneron

Faculty, Staff and Student Publications

MRI of hyperpolarized (HP) [1‐13C]pyruvate allows in vivo assessment of metabolism and has translated into human studies across diseases at 15 centers worldwide. To determine consensus on best practice for multi‐center studies for development of clinical applications. This paper presents the results of a two‐round formal consensus building exercise carried out by experts with HP [1‐13C]pyruvate human study experience. Twenty‐nine participants from 13 sites brought together expertise in pharmacy methods, MR physics, translational imaging, and data analysis with the goal of providing recommendations and best practice statements on conduct of multi‐center human studies of HP [1‐13C]pyruvate MRI. Overall, the group …

Pan-Uk Biobank Genome-Wide Association Analyses Enhance Discovery And Resolution Of Ancestry-Enriched Effects, Konrad J Karczewski, Rahul Gupta, Masahiro Kanai, Wenhan Lu, Kristin Tsuo, Ying Wang, Raymond K Walters, Patrick Turley, Shawneequa Callier, Nirav N Shah, Nikolas Baya, Duncan S Palmer, Jacqueline I Goldstein, Gopal Sarma, Matthew Solomonson, Nathan Cheng, Sam Bryant, Claire Churchhouse, Caroline M Cusick, Timothy Poterba, John Compitello, Daniel King, Wei Zhou, Cotton Seed, Hilary K Finucane, Mark J Daly, Benjamin M Neale, Elizabeth G Atkinson, Alicia R Martin

Faculty, Staff and Students Publications

Large biobanks, such as the UK Biobank (UKB), enable massive phenome by genome-wide association studies that elucidate genetic etiology of complex traits. However, individuals from diverse genetic ancestry groups are often excluded from association analyses due to concerns about population structure introducing false positive associations. Here, we generate mixed model associations and meta-analyses across genetic ancestry groups, inclusive of a larger fraction of the UKB than previous efforts, to produce freely-available summary statistics for 7,266 traits. We build a quality control and analysis framework informed by genetic architecture. Overall, we identify 14,676 significant loci (p < 5 × 10−8) in the meta-analysis that were not found in the EUR genetic ancestry group alone, including novel associations for example between CAMK2D and triglycerides. We also …

Ideate-Lung02: A Phase 3 Study Of Second-Line Ifinatamab Deruxtecan In Patients With Relapsed Small Cell Lung Cancer, Taofeek K Owonikoko, Lauren Byers, Ying Cheng, Hidetoshi Hayashi, Luis Paz-Ares, Maurice Pérol, Haichuan Hu, Meng Qian, Cecilio Roi Garcia, Juliette Godard, Mei Tang, Charles M Rudin

Faculty, Staff and Student Publications

Patients with small cell lung cancer (SCLC) have poor prognosis and limited treatment options beyond first-line therapy. B7 homolog 3 (B7-H3) is minimally expressed in normal tissues but highly expressed in SCLC. Ifinatamab deruxtecan (I-DXd), a B7-H3-directed antibody-drug conjugate, has demonstrated promising efficacy and a manageable safety profile in various tumours, including SCLC. IDeate-Lung02 is a global, randomized, open-label Phase 3 study of ~540 patients with relapsed SCLC. Adults with one prior line of platinum-based systemic therapy, ECOG performance status 0-1, and ≥1 measurable lesion (per RECIST 1.1) are eligible for study participation. Patients with asymptomatic untreated or previously treated …