Medical Specialties Commons^™

Genome-Wide Prediction Of Dominant And Recessive Neurodevelopmental Disorder-Associated Genes, Ryan S Dhindsa, Blake A Weido, Justin S Dhindsa, Arya J Shetty, Chloe F Sands, Slavé Petrovski, Dimitrios Vitsios, Anthony W Zoghbi

Duncan NRI Faculty and Staff Publications

Despite great progress, thousands of neurodevelopmental disorder (NDD) risk genes remain to be discovered. We present a computational approach that accelerates NDD risk gene identification using machine learning. First, we demonstrate that models trained solely on single-cell RNA sequencing data can robustly predict genes implicated in autism spectrum disorder (ASD), developmental and epileptic encephalopathy (DEE), and developmental delay (DD). Notably, we find differences in gene expression patterns of genes with monoallelic and bi-allelic inheritance patterns in the developing human cortex. We then integrate expression data with 300 orthogonal features, including intolerance metrics, protein-protein interaction data, and others, in a semi-supervised …

Progressive Multifocal Leukoencephalopathy (Pml) Induced By Jc Virus: A Case Report And Review Of Clinical Implications, Hugo Zamarron, Roberto Cruz

Research Symposium

Background: Progressive multifocal leukoencephalopathy (PML) is a rare but serious demyelinating disease of the central nervous system, caused by the John Cunningham (JC) virus. While the JC virus is common in the general population, it remains dormant in healthy individuals but can reactivate in immunocompromised patients, particularly those with HIV/AIDS or undergoing immunosuppressive treatments for organ transplants or autoimmune conditions. The virus attacks oligodendrocytes, leading to demyelination and significant neurological deficits. Immunosuppressive therapies such as natalizumab, rituximab, and mycophenolate increase the risk of PML. Diagnosing PML is challenging as its symptoms—focal neurological deficits, sensory-motor issues, and visual disturbances—overlap with conditions …

Carm1 Regulates Tubulin Autoregulation Through Pi3kc2Α R175 Methylation, Yena Cho, Jee Won Hwang, Mark T Bedford, Dae-Geun Song, Su-Nam Kim, Yong Kee Kim

Faculty, Staff and Student Publications

Tubulin is crucial in several cellular processes, including intracellular organization, organelle transport, motility, and chromosome segregation. Intracellular tubulin concentration is tightly regulated by an autoregulation mechanism, in which excess free tubulin promotes tubulin mRNA degradation. However, the details of how changes in free tubulin levels initiate this autoregulation remain unclear. In this study, we identified coactivator-associated arginine methyltransferase 1 (CARM1)-phosphatidylinositol 3-kinase class 2α (PI3KC2α) axis as a novel regulator of tubulin autoregulation. CARM1 stabilizes PI3KC2α by methylating its R175 residue. Once PI3KC2α is not methylated, it becomes unstable, leading to decreased cellular levels. Loss of PI3KC2α results in the release …

Photoacoustic Imaging For Image-Guided Gastric Tube Placement: Ex Vivo Characterization, Samuel John, Yeidi Yuja Vaquiz, Nikhila Nyayapathi, Loay Kabbani, Anoop Nilam, Jonathan F Lovell, Nicole A Wilson, Yan Yan, Mohammad Mehrmohammadi

Faculty, Staff and Student Publications

Over 250,000 gastrostomy tubes (G-tubes) are placed annually in the United States. Percutaneous endoscopic gastrostomy (PEG) is the most widely used clinical method for placing G-tubes within the stomach. However, endoscope detectability is limited due to the scattering of light by tissues. Poor organ visibility and low sensitivity of the palpation techniques cause blind needle insertions, which cause colon/liver perforations, abdominal bleeding, and gastric resections. Additionally, imaging artifacts and the poor distinguishability between water-filled tissues make ultrasound (US) imaging-based techniques incompatible with G-tube placement. The risk of ionizing radiation exposure and the confinement of fluoroscopy to radiology suites limits its …

Factors Driving Adolescent Tuberculosis Incidence By Age And Sex In 30 High-Tuberculosis Burden Countries: A Mathematical Modelling Study, Silvia S Chiang, Megan B Murray, Alexander W Kay, Peter J Dodd

Faculty, Staff and Students Publications

INTRODUCTION: During adolescence, tuberculosis incidence rises, with a greater increase in males compared with females. Tuberculosis notifications and estimates infrequently disaggregate adolescent age groups. Moreover, the factors that drive the increases in overall incidence and the male-to-female (MF) ratio remain unclear.

METHODS: We constructed a mechanistic model to estimate cumulative Mycobacterium tuberculosis infection and tuberculosis disease incidence in the WHO’s 30 high-tuberculosis burden countries (HBCs), which represent 86%–90% of global tuberculosis incidence. We derived infection risk from tuberculosis prevalence and assortative social mixing based on sex and age (10–14 years vs 15–19 years old). We adjusted age subgroup-specific risks of …

Response To: Correspondence On “Hyperleukocytosis In A Neuroblastoma Patient After Treatment With Natural Killer T Cells Expressing A Gd2-Specific Chimeric Antigen Receptor And Il-15” By Ataca Atilla And Atilla, Gengwen Tian, Amy N Courtney, Andras Heczey, Leonid S Metelitsa

Faculty, Staff and Students Publications

No abstract provided.

Every Jump Is A Leap Of Faith-Just Ask Evel Knievel!, Vicente Orozco-Sevilla, Joseph S Coselli

Faculty, Staff and Students Publications

No abstract provided.

A Bland–Altman Comparison Of The Lead Care® System And Inductively Coupled Plasma Mass Spectrometry For Detecting Low-Level Lead In Child Whole Blood Samples, Christina Sobin, Tanner Schaub, Natali Parisi, Eva De La Riva

Departmental Papers (PH)

Chronic childhood lead exposure, yielding blood lead levels consistently below 10 μg/dL, remains a major public health concern. Low neurotoxic effect thresholds have not yet been established. Progress requires accurate, efficient, and cost-effective methods for testing large numbers of children. The LeadCare® System (LCS) may provide one ready option. The comparability of this system to the “gold standard” method of inductively coupled plasma mass spectrometry (ICP-MS) for the purpose of detecting blood lead levels below 10 μg/dL has not yet been examined. Paired blood samples from 177 children ages 5.2–12.8 years were tested with LCS and ICP-MS. Triplicate repeat tests …

A Peculiar Pancreatitis: Investigating The Adverse Effects Of Mesalamine, Elias Arellano Villanueva, Miguel Lopez, Alhasan Asaad, Jose Campo Maldonado

Research Symposium

Background: Acute pancreatitis (AP) is a leading cause of gastrointestinal-related hospitalizations in the United States, accounting for approximately 300,000 emergency department visits annually. It is characterized by parenchymal and peripancreatic fat necrosis accompanied by inflammation. The clinical diagnosis of AP is based on elevated serum amylase and lipase levels, characteristic imaging findings, and epigastric pain often radiating to the back. While gallstones and alcohol use are the most common causes of AP, drug-induced pancreatitis (DIP) is a rare but increasingly recognized etiology, contributing to 0.1–5% of cases. DIP is typically diagnosed by excluding other causes and is often associated with …

Learning Directed Acyclic Graphs For Ligands And Receptors Based On Spatially Resolved Transcriptomic Data Of Ovarian Cancer, Shrabanti Chowdhury, Sammy Ferri-Borgogno, Peng Yang, Wenyi Wang, Jie Peng, Samuel C Mok, Pei Wang

Faculty, Staff and Student Publications

To unravel the mechanism of immune activation and suppression within tumors, a critical step is to identify transcriptional signals governing cell-cell communication between tumor and immune/stromal cells in the tumor microenvironment. Central to this communication are interactions between secreted ligands and cell-surface receptors, creating a highly connected signaling network among cells. Recent advancements in in situ-omics profiling, particularly spatial transcriptomic (ST) technology, provide unique opportunities to directly characterize ligand-receptor signaling networks that power cell-cell communication. In this paper, we propose a novel statistical method, LRnetST, to characterize the ligand-receptor interaction networks between adjacent tumor and immune/stroma cells based on ST …

Addressing Health Disparities In Hematologic Malignancies: From Genes To Outreach, Christopher R Flowers, Rachel W Anantha, Veronica Leautaud, Pinkal Desai, Chancellor E Donald, Michelle A T Hildebrandt, Jean L Koff, Rulla M Tamimi, Wendy Cozen, Chijioke Nze, Ari M Melnick

Faculty, Staff and Student Publications

This review underscores our shared responsibility to champion multidimensional strategies rooted in basic and translational science, community involvement, and societal responsiveness for a meaningful impact. Unifying themes include the need to enhance collaborative infrastructure to engage laboratory researchers, epidemiologists, data scientists, clinicians, patients, community leaders, and policymakers; patient-level support services; outreach, education, and navigation for patients at the community level; recruitment and retention of underrepresented groups in the healthcare and research workforce; and funding for these efforts.

Wernicke-Korsakoff Syndrome: A Current Perspective, Astrid-Ines Foamkom, Maria Sophia Zaraspe Malbas, Kory D. Punch, Victor A. Bob-Yellowe, Allison J. Mcadams, Julia Paz, Karina Zamora, Kelsey Baker, Ihsan Salloum, Ney Alliey-Rodriguez

Research Symposium

Background: Wernicke-Korsakoff syndrome (WKS) is a debilitating neuropsychological condition characterized by the profound loss of thiamine (vitamin B1). The neuropsychological presentation of WKS has been increasingly refined since its discovery in the nineteenth century, leading to a more robust understanding of the condition. In general, it has been shown that WKS causes differ amongst individuals but the main causes for the condition include chronic alcoholism, immunodeficiency, genetic disorders, malnutrition, drug-induced thiamine deficiency, and hyperemesis gravidarum. However, it remains unclear how demographic, environmental, and ethnic differences may influence WKS etiology and severity. Here, we sought to conduct a systematic review of …

Utilidad De La Combinación De Los Biomarcadores: Procalcitonina, Proteína C Reactiva Y Volumen Plaquetario Medio En El Diagnóstico Temprano De Sepsis Neonatal [Usefulness Of The Combination Of Biomarkers: Procalcitonin, C-Reactive Protein And Mean Platelet Volume In The Early Diagnosis Of Neonatal Sepsis], Oscar Manuel Berlanga Bolado Jr, Patricia Rivera Vazquez, Arely Socorro Hernández García, Angelica Lizbeth Martinez Ortiz

Research Symposium

Introducción: La sepsis neonatal es una causa frecuente de morbilidad y mortalidad infantil. Se le ha definido como un síndrome clínico caracterizado por signos sistémicos de infección, acompañado de bacteriemia en el primer mes de vida. Por lo tanto, el diagnóstico temprano es fundamental.

Objetivo: Conocer la sensibilidad y especificidad de la combinación de biomarcadores séricos como procalcitonina, proteína C reactiva y volumen plaquetario medio en el diagnóstico temprano de sepsis neonatal.

Material y métodos: Estudio clínico, de tipo prospectivo, predictivo, observacional, analítico, longitudinal y conveniencia. Se analizaron los biomarcadores como PCT, PCR, VPM para diagnosticar sepsis neonatal. Se incluyeron …

Gain-Of-Function Chromatin Remodeling Activity Of Oncogenic Foxl2c134w Reprograms Glucocorticoid Receptor Occupancy To Drive Granulosa Cell Tumors, Thomas Welte, Veena K Vuttaradhi, Eleonora Y Khlebus, Allison Brodsky, Alejandra Flores Legarreta, Joseph Celestino, Reid T Powell, Clifford C Stephan, Nghi Nguyen, Jian Li, Shiro Takamatsu, Katherine Calzoncinth, Anil K Sood, David M Gershenson, P Andrew Futreal, Barrett Lawson, R Tyler Hillman

Faculty, Staff and Student Publications

Adult type ovarian granulosa cell tumors (AGCT) are rare malignancies with the near universal c.C402G (p.Cys134Trp) somatic mutation in FOXL2, a forkhead box family transcription factor important for ovarian function. Relapsed AGCT is incurable, but the mechanism of the unique FOXL2 mutation could confer therapeutic vulnerabilities. To identify FOXL2C134W-dependent pharmacologic synergies, we created and characterized endogenous FOXL2 isogenic AGCT cells and an AGCT tumoroid biobank. A drug screen identified that glucocorticoids promote FOXL2C134W-dependent AGCT growth. Epigenetic investigation revealed that the Cys134Trp mutation exposes latent DNA sequence-specific chromatin remodeling activity in FOXL2. FOXL2C134W-dependent chromatin remodeling activity redirected glucocorticoid receptor chromatin occupancy …

Antibody-Drug Conjugates Targeting The Egfr Ligand Epiregulin Elicit Robust Antitumor Activity In Colorectal Cancer, Joan Jacob, Yasuaki Anami, Peyton C High, Zhengdong Liang, Shraddha Subramanian, Sukhen C Ghosh, Solmaz Aghaamiri, Cara Guernsey-Biddle, Ha Tran, Julie Rowe, Ali Azhdarinia, Kyoji Tsuchikama, Kendra S Carmon

Faculty, Staff and Student Publications

As colorectal cancer remains a leading cause of cancer-related death, identifying therapeutic targets and approaches is essential to improve patient outcomes. The EGFR ligand epiregulin (EREG) is highly expressed in RAS wild-type (WT) and mutant colorectal cancer, with minimal expression in normal tissues, making it an attractive target for antibody-drug conjugate (ADC) development. In this study, we produced and purified an EREG mAb, H231, which had high specificity and affinity for human and mouse EREG. H231 also internalized to lysosomes, which is important for ADC payload release. ImmunoPET and ex vivo biodistribution studies showed significant tumor uptake of zirconium-89-labeled H231, …

Epigenetic Landscapes Of Aging In Breast Cancer Survivors: Unraveling The Impact Of Therapeutic Interventions-A Scoping Review, Nikita Nikita, Zhengyang Sun, Swapnil Sharma, Amy L Shaver, Victoria Seewaldt, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

Breast cancer therapies have dramatically improved survival rates, but their long-term effects, especially on aging survivors, need careful consideration. This review delves into how breast cancer treatments and aging intersect, focusing on the epigenetic changes triggered by chemotherapy, radiation, hormonal treatments, and targeted therapies. Treatments can speed up biological aging by altering DNA methylation, histone modifications, and chromatin remodeling, affecting gene expression without changing the DNA sequence itself. The review explains the double-edged sword effect of therapy-induced epigenetic modifications, which help fight cancer but also accelerate aging. Chemotherapy and targeted therapies, in particular, impact DNA methylation and histone modifications, promoting …

First-In-Human Clinical Trial Of A Small-Molecule Ebna1 Inhibitor, Vk-2019, In Patients With Epstein-Barr-Positive Nasopharyngeal Cancer, With Pharmacokinetic And Pharmacodynamic Studies, A Dimitrios Colevas, Zahra Talebi, Elizabeth Winters, Caroline Even, Victor Ho-Fun Lee, Maura L Gillison, Saad A Khan, Rong Lu, Benjamin A Pinsky, Samantha S Soldan, Olga Vladmirova, Paul M Lieberman, Troy E Messick

Faculty, Staff and Student Publications

Purpose: A first-in-human phase I study was conducted in patients with nasopharyngeal carcinoma to assess the safety and tolerability of VK-2019, a small-molecule selective inhibitor of Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1).

Patients and methods: Pharmacokinetic and pharmacodynamic studies were performed, including the measurement of EBV DNA plasma levels. Twenty-three patients received VK-2019 orally once daily at doses ranging from 60 to 1,800 mg using an accelerated titration design, with cohort expansion at 1,800 mg. EBV genome copy number and spatial transcriptomic analyses were conducted on biopsies collected from three patients at baseline and after treatment.

Results: VK-2019 was …

Ancestral Differences In Anticancer Treatment Efficacy And Their Underlying Genomic And Molecular Alterations, Mei Luo, Jingwen Yang, Alejandro A Schäffer, Chengxuan Chen, Yuan Liu, Yamei Chen, Chunru Lin, Lixia Diao, Yong Zang, Yanyan Lou, Huda Salman, Gordon B Mills, Eytan Ruppin, Leng Han

Faculty, Staff and Student Publications

Systematic multi-omics analysis revealed ancestry-dependent molecular alterations, but their impact on the efficacy of anti-cancer treatment is yet largely unknown. Here, we analyzed clinical trials from ClinicalTrials.gov and found that only 8,779/102,721 (8.5%) oncology clinical trials posted information on enrollment by race/ethnicity. The underrepresentation of non-White populations suggests that it remains challenging to determine differences in the efficacy of anti-tumor treatments among different racial groups. Through a comprehensive analysis of clinically actionable genes, imputed drug responses, and immune features, we identified potential differences in treatment response to targeted, chemo and immunotherapies between different ancestral populations. Further analysis of multiple independent …

Pleural Effusion: Shedding Light On Pleural Disease Beyond Infection And Malignancy, William C Harding, Abdul R Halawa, Mazen M Aiche, Bilal Zafar, Hyeon-Ju R Ali, Lara Bashoura, Saadia A Faiz

Faculty, Staff and Student Publications

Background and Objectives: Non-malignant pleural effusions (NMPEs) are the most frequently encountered pleural disease. They arise from various non-malignant, non-infectious clinical conditions, including cardiac, renal, and hepatic organ dysfunction. Despite their wide prevalence, there is a lack of literature for NMPE. This publication aims to provide an updated overview of the causes, diagnostic strategies, and management options for NMPE.

Materials and Methods: This review synthesizes findings from studies published on NMPE, focusing on the presentation, diagnosis (such as imaging and pleural fluid analysis), and management strategies. Studies were selected based on relevance and were analyzed to provide a comprehensive summary …

Targeted Normoxemia And Supplemental Oxygen-Free Days In Critically Injured Adults: A Stepped-Wedge Cluster Randomized Clinical Trial, David J Douin, John D Rice, Erin L Anderson, Conner L Jackson, Alex C Cheng, Mengli Xiao, Jessica Cwik, Laurel E Beaty, Jessica L Wild, Mohamud R Daya, Pratik B Doshi, Shannon C Eastham, Michael D Goodman, Scott R Gunn, Jason S Haukoos, Jessica A Hudson, Jan O Jansen, Jason T Mcmullan, Julie A Rizzo, Martin A Schreiber, Wesley H Self, Matthew W Semler, Aimee Steinwand, Nicole Werner, Vikhyat S Bebarta, Steven G Schauer, Adit A Ginde

Faculty, Staff and Student Publications

Importance: Supplemental oxygen is fundamental to caring for critically injured adults but can expose them to excess inspired oxygen.

Objective: To determine the safety and effectiveness of targeting normoxemia in critically ill trauma patients.

Design, setting, and participants: This multicenter, stepped-wedge, cluster randomized clinical trial compared targeted normoxemia (defined as a peripheral oxygen saturation [Spo2] of 90% to 96%) with usual care among adult trauma patients admitted to an intensive care unit (ICU) at 8 level I trauma centers across the US. These trauma centers were randomized at 3-month intervals when they crossed over from usual care to targeting normoxemia. …

Accumulation Of Cd38 In Hybrid Epithelial/Mesenchymal Cells Promotes Immune Remodeling And Metastasis In Breast Cancer, Tanvi H Visal, Recep Bayraktar, Petra Den Hollander, Michael A Attathikhun, Tieling Zhou, Jing Wang, Li Shen, Corina-Elena Minciuna, Meng Chen, Elizve Barrientos-Toro, Harsh Batra, Maria Gabriela Raso, Fei Yang, Edwin R Parra, Aysegul A Sahin, George A Calin, Sendurai A Mani

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer. The epithelial-to-mesenchymal transition is a nonbinary process in the metastatic cascade that generates tumor cells with both epithelial and mesenchymal traits known as hybrid EM cells. Recent studies have elucidated the enhanced metastatic potential of cancers featuring the hybrid EM phenotype, highlighting the need to uncover molecular drivers and targetable vulnerabilities of the hybrid EM state. Here, we discovered that hybrid EM breast tumors are enriched in CD38, an immunosuppressive molecule associated with worse clinical outcomes in liquid malignancies. Altering CD38 expression in tumor cell impacted migratory, invasive, …

A Novel Sensitivity Maximization At A Given Specificity Method For Binary Classifications, Seyyed Mahmood Ghasemi, Chunhui Gu, Johannes F Fahrmann, Samir Hanash, Kim-Anh Do, James P Long, Ehsan Irajizad

Faculty, Staff and Student Publications

In the cancer early detection field, logistic regression (LR) is a frequently used approach to establish a combination rule that differentiates cancer from noncancer. However, the application of LR relies on a maximum likelihood approach, which may not yield optimal combination rules for maximizing sensitivity at a clinically desirable specificity and vice versa. In this article, we have developed an improved regression framework, sensitivity maximization at a given specificity (SMAGS), for binary classification that finds the linear decision rule, yielding the maximum sensitivity for a given specificity or the maximum specificity for a given sensitivity. We additionally expand the framework …

Recovery Potential In Patients After Cardiac Arrest Who Die After Limitations Or Withdrawal Of Life Support, Jonathan Elmer, Patrick J Coppler, Cecelia Ratay, Alexis Steinberg, Sara Difiore-Sprouse, Nicholas Case, Baruch Fischhoff, Maria De-Arteaga, Alain Cariou, Alejandro A Rabinstein, Andrea O Rossetti, Ankur A Doshi, Bradley J Molyneaux, Cameron Dezfulian, Carolina B Maciel, Christoph Leithner, Cindy H Hsu, Claudio Sandroni, David M Greer, David B Seder, Francis X Guyette, Fabio Silvio Taccone, Hiromichi Naito, Jasmeet Soar, Jean-Baptiste Lascarrou, Jerry P Nolan, Karen G Hirsch, Katherine M Berg, Marion Moseby-Knappe, Markus B Skrifvars, Michael C Kurz, Min Jung Kathy Chae, Mypinder S Sekhon, Nicholas J Johnson, Pedro Kurtz, Romergryko G Geocadin, Sachin Agarwal, Teresa L May, Theresa M Olasveengen, Clifton W Callaway, Optimizing Recovery Prediction After Cardiac Arrest (Orca) Study Group

Faculty, Staff and Students Publications

Importance: Understanding the relationship between patients' clinical characteristics and outcomes is fundamental to medicine. When critically ill patients die after withdrawal of life-sustaining therapy (WLST), the inability to observe the potential for recovery with continued aggressive care could bias future clinical decisions and research.

Objective: To quantify the frequency with which experts consider patients who died after WLST following resuscitated cardiac arrest to have had recovery potential if life-sustaining therapy had been continued.

Design, setting, and participants: This prospective cohort study included comatose adult patients (aged ≥18 years) treated following resuscitation from cardiac arrest at a single academic medical center …

Debating The Risks And Benefits Of Firearms In The Us-Make The Other Side Panicky, Cedric Dark

Faculty, Staff and Students Publications

No abstract provided.

Children Suspected For Developmental Coordination Disorder In Hong Kong And Associated Health-Related Functioning: A Survey Study, Kathlynne F. Eguia, Sum Kwing Cheung, Kevin K.H. Chung, Catherine M. Capio

Health Sciences Faculty Publications

Children with developmental coordination disorder (DCD) have motor difficulties that interfere with their daily functions. The extent to which DCD affects children in Hong Kong has not been established. In this study, we aimed to estimate the prevalence of children suspected of DCD (sDCD) in Hong Kong and to examine the relationship between motor performance difficulties and health-related functioning. We conducted a cross-sectional survey of parents of children aged 5 to 12 years across Hong Kong (N = 656). The survey consisted of the Developmental Coordination Disorder Questionnaire (DCDQ) and short forms on global health, physical activity, positive affect, and …

Exploring Oxylipins In Host–Microbe Interactions And Their Impact On Infection And Immunity, Robert J. Neff, Christopher D. Radka

Markey Cancer Center Faculty Publications

Plasma lipids are essential components of biological systems, transported through interactions with proteins to maintain cellular functions. These lipids exist in various forms, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenol lipids, derived from dietary intake, adipose tissue, and biosynthesis. While the association between certain fatty acids and cardiovascular diseases has been widely recognized, polyunsaturated fatty acids (PUFAs) exhibit cardioprotective effects, reducing risks of arrhythmias and heart-related mortality. This is due to their role in the production of eicosanoids, which modulate inflammation. Chronic inflammation, particularly in obesity, is significantly influenced by fatty acids, with saturated fatty acids promoting …

Functional Investigation Of A Putative Calcium-Binding Site Involved In The Inhibition Of Inositol 1,4, 5-Trisphosphate Receptor Activity, Vikas Arige, Larry E Wagner, Sundeep Malik, Mariah R Baker, Guizhen Fan, Irina I Serysheva, David I Yule

Faculty, Staff and Student Publications

The regulation of inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) activity is thought to define the spatiotemporal patterns of Ca2+ signals necessary for the appropriate activation of downstream effectors. The binding of both IP3 and Ca2+ is obligatory for IP3R channel opening. Ca2+ however regulates IP3R activity in a biphasic manner. Ca2+ binding to a high-affinity pocket formed by the third armadillo repeat domain and linker domain promotes IP3R channel opening without altering the Ca2+ dependency for channel inactivation. These data suggest that a distinct low-affinity Ca2+-binding site is responsible for the reduction in IP3R activity at higher [Ca2+]. We mutated a …

Awareness On Environmental Air Pollution Among Adults In Rural Mysuru, Rakesh M, Jesymol Joy, Sunil Kumar D

Digital Journal of Clinical Medicine

Introduction

Air pollution is a major environmental threat and one of the main cases of death among all risk factors known so far. Health effects also include preterm and low-birthweight, asthma as well as cognitive and neurological impairment basically having the potential to impact our whole body, way beyond our lungs. The proposed study focusses on to assess the awareness on air pollution and factors associated with it among adults in South Mysuru which can put a light on the preventive measures and policies to be taken by the individuals as well as the authorities.

Methodology

A Community-based cross-sectional study …

Safety And Efficacy Of Dtx401, An Aav8-Mediated Liver-Directed Gene Therapy, In Adults With Glycogen Storage Disease Type I A (Gsdia), David A Weinstein, Terry G Derks, David F Rodriguez-Buritica, Ayesha Ahmad, María-Luz Couce, John J Mitchell, Rebecca Riba-Wolman, Malaya Mount, Julieta Bonvin Sallago, Katalin M Ross, Melanie M Van Der Klauw, Foekje De Boer, Caroline Van Der Schaaf, Heather Saavedra, Miguel Martínez-Olmos, Elvis Atanga, Asad Hosseini, Deepali Mitragotri, Eric Crombez

Faculty, Staff and Student Publications

Glycogen storage disease type Ia (GSDIa) is a rare, life‐threatening, inherited carbohydrate metabolism disorder caused by glucose‐6‐phosphatase (G6Pase) deficiency, which is essential for glycogenolysis and gluconeogenesis. GSDIa management includes a strict medically prescribed diet that typically includes daily uncooked cornstarch doses, including overnight, to maintain euglycemia. DTX401 is an investigational adeno‐associated virus serotype 8 vector expressing the human G6PC1 gene that encodes G6Pase. This open‐label, phase 1/2, dose‐escalation, 52‐week gene therapy trial evaluated the safety and efficacy of a single DTX401 infusion in 12 adults with GSDIa (ClinicalTrials.gov Identifier: NCT03517085). Three participants in Cohort 1 received DTX401 2.0 × …

Bevacizumab Beyond Progression: Impact Of Subsequent Bevacizumab Re-Treatment In Patients With Ovarian, Fallopian Tube, And Peritoneal Cancer After Progression, Amma Asare, Rebecca Ann Previs, Daniel Spinosa, Bryan Fellman, Amelia L Scott, Isabelle Mulder, May Mahmoud, Ahmed Enbaya, Jean Hansen Siedel, Lauren Cobb, Pamela T Soliman, Anil K Sood, Robert L Coleman, Angeles Alvarez Secord, Shannon N Westin

Faculty, Staff and Student Publications

Background: This study evaluated whether patients with epithelial ovarian, fallopian tube, and primary peritoneal carcinoma (OC) who are immediately re-treated with bevacizumab derive benefit after disease progression on a bevacizumab-containing regimen.

Methods: This multi-institutional, retrospective study compared patients with high grade non-mucinous epithelial OC who received bevacizumab followed directly by another bevacizumab-containing treatment regimen to patients who received bevacizumab followed by a regimen that did not contain bevacizumab (or received no further treatment). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier product-limit estimator and modeled via Cox proportional hazards regression.

Results: Among 226 patients with OC …