Medicine and Health Sciences Commons^™

Neuronal Alpha-Synuclein Disease Integrated Staging System Performance In Ppmi, Pasadena, And Spark Baseline Cohorts, Tien Dam, Gennaro Pagano, Michael C Brumm, Caroline Gochanour, Kathleen L Poston, Daniel Weintraub, Lana M Chahine, Christopher Coffey, Caroline M Tanner, Catherine M Kopil, Yuge Xiao, Sohini Chowdhury, Luis Concha-Marambio, Peter Dibiaso, Tatiana Foroud, Mark Frasier, Danna Jennings, Karl Kieburtz, Kalpana Merchant, Brit Mollenhauer, Thomas J Montine, Kelly Nudelman, John Seibyl, Todd Sherer, Andrew Singleton, Diane Stephenson, Matthew Stern, Claudio Soto, Eduardo Tolosa, Andrew Siderowf, Billy Dunn, Tanya Simuni, Kenneth Marek, Parkinson’S Progression Markers Initiative Collaborators

Faculty, Staff and Student Publications

The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson's disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1741 participants had SAA data and of these 1030 (59%) were S+ consistent …

Use Of Web-Based Decision Support To Improve Informed Choice For Chemoprevention: A Qualitative Analysis Of Pre-Implementation Interviews (Swog S1904), Alissa M Michel, Haeseung Yi, Jacquelyn Amenta, Nicole Collins, Anna Vaynrub, Subiksha Umakanth, Garnet Anderson, Katie Arnold, Cynthia Law, Sandhya Pruthi, Ana Sandoval-Leon, Rachel Shirley, Maria Grosse Perdekamp, Sarah Colonna, Stacy Krisher, Tari King, Lisa D Yee, Tarah J Ballinger, Christa Braun-Inglis, Debra A Mangino, Kari Wisinski, Claudia A Deyoung, Masey Ross, Justin Floyd, Andrea Kaster, Lindi Vanderwalde, Thomas J Saphner, Corrine Zarwan, Shelly Lo, Cathy Graham, Alison Conlin, Kathleen Yost, Doreen Agnese, Cheryl Jernigan, Dawn L Hershman, Marian L Neuhouser, Banu Arun, Katherine D Crew, Rita Kukafka

Faculty, Staff and Student Publications

Background: Women with high-risk breast lesions, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have a 4- to tenfold increased risk of breast cancer compared to women with non-proliferative breast disease. Despite high-quality data supporting chemoprevention, uptake remains low. Interventions are needed to break down barriers.

Methods: The parent trial, MiCHOICE, is a cluster randomized controlled trial evaluating the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. For this pre-implementation analysis, 25 providers participated in semi-structured interviews prior to accessing decision support tools. …

Usf2 And Tfeb Compete In Regulating Lysosomal And Autophagy Genes, Jaebeom Kim, Young Suk Yu, Yehwa Choi, Do Hui Lee, Soobin Han, Junhee Kwon, Taichi Noda, Masahito Ikawa, Dongha Kim, Hyunkyung Kim, Andrea Ballabio, Keun Il Kim, Sung Hee Baek

Duncan NRI Faculty and Staff Publications

Autophagy, a highly conserved self-digestion process crucial for cellular homeostasis, is triggered by various environmental signals, including nutrient scarcity. The regulation of lysosomal and autophagy-related processes is pivotal to maintaining cellular homeostasis and basal metabolism. The consequences of disrupting or diminishing lysosomal and autophagy systems have been investigated; however, information on the implications of hyperactivating lysosomal and autophagy genes on homeostasis is limited. Here, we present a mechanism of transcriptional repression involving upstream stimulatory factor 2 (USF2), which inhibits lysosomal and autophagy genes under nutrient-rich conditions. We find that USF2, together with HDAC1, binds to the CLEAR motif within lysosomal …

The Association Of The Oral Microbiota With Cognitive Functioning In Adolescence, Oxana Y Naumova, Pavel V Dobrynin, Galina V Khafizova, Elena L Grigorenko

Faculty, Staff and Students Publications

Background: A growing body of research supports the role of the microbial communities residing in the digestive system in the host's cognitive functioning. Most of these studies have been focused on the gut microbiome and its association with clinical phenotypes in middle-aged and older adults. There is an insufficiency of population-based research exploring the association of normative cognitive functioning with the microbiome particularly with the oral microbiota.

Methods: In this study, using metagenomics and metabolomics, we characterized the salivary microbiome diversity in a sample of 51 males of Hispanic and African American origin aged 12-18 years and explored …

Prevalence Of Cardiometabolic Risk Factors In Women: Insights From The Houston Heartreach Study, Arjun R Raghuram, Matthew W Segar, Stephanie Coulter, Joseph G Rogers

The Texas Heart Institute Journal

BACKGROUND: Cardiovascular disease is the leading cause of death among women in the United States. Past research has highlighted the importance of the relationship between female-specific demographics and traditional risk factors. The present analysis aimed to identify the prevalence of modifiable risk factors in women attending a community cardiovascular health screening.

METHODS: Data collected between 2011 and 2019 were obtained from the Houston HeartReach Registry. Participants were classified as having or not having each of 4 traditional cardiometabolic risk factors: hypertension, diabetes, body mass index indicating overweight or obesity, and dyslipidemia. Differences in prevalence were compared using the Pearson χ2 …

Sequencing-Based Detection Of Avian Influenza A(H5n1) Virus In Wastewater In Ten Cities, Michael J Tisza, Blake M Hanson, Justin R Clark, Li Wang, Katelyn Payne, Matthew C Ross, Kristina D Mena, Anna Gitter, Sara J Javornik Cregeen, Juwan Cormier, Vasanthi Avadhanula, Austen Terwilliger, John Balliew, Fuqing Wu, Janelle Rios, Jennifer Deegan, Pedro A Piedra, Joseph F Petrosino, Eric Boerwinkle, Anthony W Maresso

Faculty, Staff and Student Publications

No abstract provided.

Study Protocol For Writing To Heal: A Culturally Based Brief Expressive Writing Intervention For Chinese Immigrant Breast Cancer Survivors, Qian Lu, Di Lun, Lenna Dawkins-Moultin, Yisheng Li, Minxing Chen, Sharon Hermes Giordano, James W Pennebaker, Lucy Young, Carol Wang

Faculty, Staff and Student Publications

BACKGROUND: This study uses a randomized controlled trial (RCT) to test the health benefits of expressive writing that is culturally adapted for Chinese immigrant breast cancer survivors (BCSs) and to characterize how acculturation moderates the effects of expressive writing interventions.

METHODS: We will recruit Chinese immigrant BCSs (N = 240) diagnosed with stage 0-III breast cancer and within 5 years of completion of primary treatment. Recruitment will occur primarily through community-based organizations and cancer registries. Participants will be randomly assigned either to a control condition to write about neutral topics or to one of two intervention conditions, self-regulation or self-cultivation, …

Effect Of An In-Home Palivizumab Administration Program For Children With Medical Complexity, Hina Emanuel, Aravind Yadav, Julie C Eapan, Maria Caldas-Vasquez, Tomika S Harris, Katrina Mcbeth, Fatima Boricha, Janice John, Ivan G Magana Ceballos, Giuseppe N Colasurdo, Maria E Tellez, Tina Reddy, Wilfredo De Jesús-Rojas, Ricardo A Mosquera

Faculty, Staff and Student Publications

Background: In-home palivizumab administration programs (PH) have shown promise in reducing RSV-associated infections. These programs may be particularly beneficial for children with medical complexity (CMC) by limiting their exposure to healthcare-associated infections (HAIs) from non-RSV-related pathogens during transportation and visits to medical facilities.

Methods: In this prospective study, 41 children with CMC less than 2 years of age were randomized by their health insurance to receive PH or in the clinic (PC) during the RSV season (October 2018-April 2019). Patients were stratified by home ventilation. The primary outcome was the total number of face-to-face encounters. Secondary outcomes were unscheduled clinic …

Using Syndromic Surveillance For Unintentional And Undetermined Intent Drowning Surveillance In A Large Metropolitan Area, Rohit P Shenoi, Briana Moreland, Jennifer L Jones, Nicholas Peoples, Elizabeth A Camp, Ned Levine

Faculty, Staff and Students Publications

INTRODUCTION: A drowning definition is available for use with National Syndromic Surveillance Program (NSSP) data. However, its accuracy in capturing drowning emergency department and urgent care visits at the regional level is unknown. We tested the ability of the syndromic surveillance (SS) definition in capturing unintentional and undetermined intent drowning (UUID) and describe UUID SS visit trends in a large metropolitan area.

METHODS: We applied the drowning definition to NSSP data from 2016 to 2022 for the 8-county metropolitan Houston region. We queried the dataset for UUID ICD-10-CM codes and manually reviewed the chief complaint (CC) and discharge diagnosis (DD) …

Chronic Graft-Versus-Host Disease: Unresolved Complication Or Ancient History?, Joseph A Pidala, Ted A Gooley, Leo Luznik, Bruce R Blazar

Faculty, Staff and Students Publications

Chronic graft-versus-host disease (cGVHD) is associated with morbidity, mortality, impaired quality of life, prolonged immunosuppressive therapy, and infection risk after allogeneic hematopoietic cell transplantation (HCT). Major strides have occurred in the understanding of cGVHD biology; National Institutes of Health Consensus meetings have refined rigorous approaches to diagnosis, staging, and response criteria; major interventional trials have established standard benchmarks for treatment outcome; and 3 agents to date have been US Food and Drug Administration approved for treating corticosteroid-refractory cGVHD. Promising results from several recent trials have led some, but not others, to conclude that the risk of developing cGVHD is sufficiently …

Untargeted Metabolomic Biomarker Discovery For The Detection Of Ectopic Pregnancy, Onur Turkoglu, Ayse Citil, Ceren Katar, Ismail Mert, Robert A Quinn, Ray O Bahado-Singh, Stewart F Graham

Faculty, Staff and Students Publications

Ectopic pregnancy (EP) is the leading cause of maternal morbidity and mortality in the first trimester. Using an untargeted metabolomic approach, we sought to identify putative plasma biomarkers using tandem liquid chromatography-mass spectrometry for the detection of tubal EP. This case-control study included the prospective recruitment of 50 tubal EP cases and 50 early intrauterine pregnancy controls. To avoid over-fitting, logistic regression models were developed in a randomly selected discovery group (30 cases vs. 30 controls) and validated in the test group (20 cases vs. 20 controls). In total, 585 mass spectral features were detected, of which 221 molecular features …

Sequencing-Based Detection Of Avian Influenza A(H5n1) Virus In Wastewater In Ten Cities, Michael J Tisza, Blake M Hanson, Justin R Clark, Li Wang, Katelyn Payne, Matthew C Ross, Kristina D Mena, Anna Gitter, Sara J Javornik Cregeen, Juwan Cormier, Vasanthi Avadhanula, Austen Terwilliger, John Balliew, Fuqing Wu, Janelle Rios, Jennifer Deegan, Pedro A Piedra, Joseph F Petrosino, Eric Boerwinkle, Anthony W Maresso

Faculty, Staff and Students Publications

No abstract provided.

Molecular Testing Of Environmental Samples As A Potential Source To Estimate Parasite Infection, Rojelio Mejia, Barton Slatko, Cristina Almazan, Ruben Cimino, Alejandro Krolewiecki, Natalia Montellano Duran, Jacob Edwin Valera Aspetty, Paola Andrea Vargas, Chiara Cássia Oliveira Amorim, Stefan Michael Geiger, Ricardo Toshio Fujiwara, Juan David Ramirez, Luz Marina Llangarí-Arizo, Irene Guadalupe, Liliana E Villanueva-Lizama, Julio Vladimir Cruz-Chan, María Leticia Ojeda, Eva Mereles Aranda, Sandra Ocampos Benedetti, Maritza Dalí Camones Rivera, Eddyson Montalvo Sabino, Carlos Pineda, Eric J Wetzel, Philip J Cooper

Faculty, Staff and Students Publications

We discuss the potential usefulness of molecular testing of soil, dust, and water samples to detect medically important parasites, and where such testing could be used to supplement stool sampling in humans. A wide variety of parasites including protozoa and helminths, many of which are zoonotic, have an important infection reservoir in the environment. In some cases, this environmental period is essential for further parasite development. We describe the progress in implementing methods for the molecular detection of these parasites in soil across eight collaborating centers in Latin America and represent a variety of potential applications in improving our understanding …

An Approach To Analyze Spatiotemporal Patterns Of Gene Expression At Single-Cell Resolution In Candida Albicans-Infected Mouse Tongues, Elena Lindemann-Perez, Diana L Rodríguez, J Christian Pérez

Faculty, Staff and Student Publications

Microbial gene expression measurements derived from infected organs are invaluable to understand pathogenesis. However, current methods are limited to "bulk" analyses that neglect microbial cell heterogeneity and the lesion's spatial architecture. Here, we report the use of hybridization chain reaction RNA fluorescence in situ hybridization (HCR RNA-FISH) to visualize and quantify Candida albicans transcripts at single-cell resolution in tongues of infected mice. The method is compatible with fixed-frozen and formalin-fixed paraffin-embedded tissues. We document cell-to-cell variation and intriguing spatiotemporal expression patterns for C. albicans mRNAs that encode products implicated in oral candidiasis. The approach provides a spatial dimension to gene …

B Cells Drive Neuropathic Pain-Related Behaviors In Mice Through Igg-Fc Gamma Receptor Signaling, Michael J Lacagnina, Kendal F Willcox, Nabila Boukelmoune, Alexis Bavencoffe, Ishwarya Sankaranarayanan, Daniel T Barratt, Younus A Zuberi, Dorsa Dayani, Melissa V Chavez, Jonathan T Lu, Alex Bersellini Farinotti, Stephanie Shiers, Allison M Barry, Juliet M Mwirigi, Diana Tavares-Ferreira, Geoffrey A Funk, Anna M Cervantes, Camilla I Svensson, Edgar T Walters, Mark R Hutchinson, Cobi J Heijnen, Theodore J Price, Nathan T Fiore, Peter M Grace

Faculty, Staff and Student Publications

Neuroimmune interactions are essential for the development of neuropathic pain, yet the contributions of distinct immune cell populations have not been fully unraveled. Here, we demonstrate the critical role of B cells in promoting mechanical hypersensitivity (allodynia) after peripheral nerve injury in male and female mice. Depletion of B cells with a single injection of anti-CD20 monoclonal antibody at the time of injury prevented the development of allodynia. B cell-deficient (muMT) mice were similarly spared from allodynia. Nerve injury was associated with increased immunoglobulin G (IgG) accumulation in ipsilateral lumbar dorsal root ganglia (DRGs) and dorsal spinal cords. IgG was …

Nutrition Management In Children Less Than 5 Years Of Age With Glycogen Storage Disease Type I: Survey Results, Mary Sowa, Monica Boyer, Jessica Green, Surekha Pendyal, Heather Saavedra

Faculty, Staff and Student Publications

Background: Nutrition management for GSD Type I (GSDI; OMIM #232200, 232220) is complex, with the goal being to maintain euglycemia while minimizing metabolic derangements. Management guidelines were published in 2002 and 2014. However, there is limited information on the nuances of nutrition management and the unique feeding challenges of children.

Methods: A REDCap survey focusing on staffing and current practices in the nutrition management of children with GSD I who were < 5 years of age was sent to the metabolic dietitian's listserv and GMDI membership in 8/2023.

Results: There were 21 North American respondents. In 17/21 clinics (81%), Prosobee® was the primary choice for infant formula. Dietitians used different methods to determine hourly glucose needs. Fasting …

Transient Elastography And Diffusion-Weighted Magnetic Resonance Imaging For Assessment Of Liver Fibrosis In Children With Chronic Hepatitis C, Mohamed A El-Guindi, Alif A Allam, Ahmed A Abdel-Razek, Gihan A Sobhy, Menan E Salem, Mohamed A Abd-Allah, Mostafa M Sira

Faculty, Staff and Student Publications

BACKGROUND: Chronic hepatitis C (CHC) is a health burden with consequent morbidity and mortality. Liver biopsy is the gold standard for evaluating fibrosis and assessing disease severity and prognostic purposes post-treatment. Noninvasive alternatives for liver biopsy such as transient elastography (TE) and diffusion-weighted magnetic resonance imaging (DW-MRI) are critical needs.

AIM: To evaluate TE and DW-MRI as noninvasive tools for predicting liver fibrosis in children with CHC.

METHODS: This prospective cross-sectional study initially recruited 100 children with CHC virus infection. Sixty-four children completed the full set of investigations including liver stiffness measurement (LSM) using TE and measurement of apparent diffusion …

Chatgpt Provides Acceptable Responses To Patient Questions Regarding Common Shoulder Pathology, Umar Ghilzai, Benjamin Fiedler, Abdullah Ghali, Aaron Singh, Benjamin Cass, Allan Young, Adil Shahzad Ahmed

Faculty, Staff and Students Publications

BACKGROUND: ChatGPT is rapidly becoming a source of medical knowledge for patients. This study aims to assess the completeness and accuracy of ChatGPT's answers to the most frequently asked patients' questions about shoulder pathology.

METHODS: ChatGPT (version 3.5) was queried to produce the five most common shoulder pathologies: biceps tendonitis, rotator cuff tears, shoulder arthritis, shoulder dislocation and adhesive capsulitis. Subsequently, it generated the five most common patient questions regarding these pathologies and was queried to respond. Responses were evaluated by three shoulder and elbow fellowship-trained orthopedic surgeons with a mean of 9 years of independent practice, on Likert scales …

Dense And Persistent Odor Representations In The Olfactory Bulb Of Awake Mice, Delaram Pirhayati, Cameron L Smith, Ryan Kroeger, Saket Navlakha, Paul Pfaffinger, Jacob Reimer, Benjamin R Arenkiel, Ankit Patel, Elizabeth H Moss

Children’s Nutrition Research Center Staff Publications

Recording and analysis of neural activity are often biased toward detecting sparse subsets of highly active neurons, masking important signals carried in low-magnitude and variable responses. To investigate the contribution of seemingly noisy activity to odor encoding, we used mesoscale calcium imaging from mice of both sexes to record odor responses from the dorsal surface of bilateral olfactory bulbs (OBs). The outer layer of the mouse OB is comprised of dendrites organized into discrete "glomeruli," which are defined by odor receptor-specific sensory neuron input. We extracted activity from a large population of glomeruli and used logistic regression to classify odors …

Skin In The Game: A Review Of Single-Cell And Spatial Transcriptomics In Dermatological Research, Samuel Schepps, Jonathan Xu, Henry Yang, Jenna Mandel, Jaanvi Mehta, Julianna Tolotta, Nicole Baker, Volkan Tekmen, Neda Nikbakht, Paolo Fortina, Ignacia Fuentes, Bonnie Lafleur, Raymond J Cho, Andrew P South

Staff and Researcher Publications

Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) are two emerging research technologies that uniquely characterize gene expression microenvironments on a cellular or subcellular level. The skin, a clinically accessible tissue composed of diverse, essential cell populations, serves as an ideal target for these high-resolution investigative approaches. Using these tools, researchers are assembling a compendium of data and discoveries in healthy skin as well as a range of dermatologic pathophysiologies, including atopic dermatitis, psoriasis, and cutaneous malignancies. The ongoing advancement of single-cell approaches, coupled with anticipated decreases in cost with increased adoption, will reshape dermatologic research, profoundly influencing disease characterization, …

Cd103+ Cdc1 Dendritic Cell Vaccine Therapy For Osteosarcoma Lung Metastases, Yuanzheng Yang, Yifan Zhou, Jian Wang, You Zhou, Stephanie S Watowich, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Background: We generated a CD103+DC vaccine using K7M3 OS cell lysates (cDCV) and investigated its ability to induce regression of primary tumors, established lung metastases, and a systemic immune response. Methods: A bilateral tumor model was used to assess cDCV therapy efficacy and systemic immunity induction. K7M3 cells were injected into mice bilaterally. Right-sided tumors received PBS (control) or cDCV. Left-sided tumors were untreated. Tumor growth was compared between the vaccine-treated and untreated tumor on the contralateral side and compared to the control group. The immune cell profiles of the tumors, and tumor-draining lymph nodes (TdLNs) and spleen were evaluated. …

In Vivo Crispr Screens Identify Mga As An Immunotherapy Target In Triple-Negative Breast Cancer, Xu Feng, Chang Yang, Yuanjian Huang, Dan Su, Chao Wang, Lori Lyn Wilson, Ling Yin, Mengfan Tang, Siting Li, Zhen Chen, Dandan Zhu, Shimin Wang, Shengzhe Zhang, Jie Zhang, Huimin Zhang, Litong Nie, Min Huang, Jae-Il Park, Traver Hart, Dadi Jiang, Kuirong Jiang, Junjie Chen

Faculty, Staff and Student Publications

Understanding the mechanisms underlying immune evasion is crucial for developing novel anticancer modalities. To systematically uncover tumor-intrinsic genetic modulators involved in immune escape in tumor microenvironment, we performed genome-scale in vivo CRISPR screens in two syngeneic models and later expanded up to seven syngeneic models with a focused validation library. These data help us better understand tumor immune evasion and pave the way for developing effective therapeutics. Importantly, we uncovered that Mga depletion elicited an antitumor immune response and inhibited tumor growth in triple-negative breast cancer. Our findings suggest that Mga may play a role in modulating the tumor immune …

Stimulation Of An Entorhinal-Hippocampal Extinction Circuit Facilitates Fear Extinction In A Post-Traumatic Stress Disorder Model, Ze-Jie Lin, Xue Gu, Wan-Kun Gong, Mo Wang, Yan-Jiao Wu, Qi Wang, Xin-Rong Wu, Xin-Yu Zhao, Michael X Zhu, Lu-Yang Wang, Quanying Liu, Ti-Fei Yuan, Wei-Guang Li, Tian-Le Xu

Faculty, Staff and Student Publications

Effective psychotherapy of post-traumatic stress disorder (PTSD) remains challenging owing to the fragile nature of fear extinction, for which the ventral hippocampal CA1 (vCA1) region is considered as a central hub. However, neither the core pathway nor the cellular mechanisms involved in implementing extinction are known. Here, we unveil a direct pathway, where layer 2a fan cells in the lateral entorhinal cortex (LEC) target parvalbumin-expressing interneurons (PV-INs) in the vCA1 region to propel low-gamma-band synchronization of the LEC-vCA1 activity during extinction learning. Bidirectional manipulations of either hippocampal PV-INs or LEC fan cells sufficed for fear extinction. Gamma entrainment of vCA1 …

Predictors Of Transition From Child And Adolescent Bipolar Not Otherwise Specified To Bipolar I Disorder, A Longitudinal 3.9-Year Study., María Ribeiro-Fernández, Azucena Díez-Suárez, Kiki D Chang, Cesar A Soutullo

Faculty, Staff and Student Publications

Background: Children and adolescents with subthreshold manic symptoms not meeting full DSM criteria for bipolar I or II disorder (BP-I or BP-II) are classified as unspecified bipolar disorder (formerly bipolar not otherwise specified: BP-NOS). Factors associated with transition from BP-II or NOS to BP-I may predict the progression of the disorder. Our objective is to analyze factors associated with transition to BP-I in a Spanish sample of youth with BP-NOS or BP-II.

Methods: We included all youth diagnosed with BP before 18 years of age presenting to our clinic (October 1999-December 2014). We assessed clinical factors that may predict transition …

A Review Of Studies On Hiv Pre-Exposure Prophylaxis In Community Pharmacies In States With Restrictive Pharmacist Prescription Authority In The United States, Hongmei Wang, Dominique Guinn, Xavier Roshitha Ramisetty, Thomas P Giordano, Ivy O Poon

Faculty, Staff and Students Publications

Community pharmacies have unparalleled potential to increase access to pre-exposure prophylaxis medications (PrEP) for HIV prevention; however, only 17 out of 50 states in the United States have statewide authority for pharmacists to provide PrEP at community pharmacies. Few studies have reported on how pharmacists overcome the legislative barrier and provide PrEP services in restrictive pharmacy prescription states. The objective of this article is to identify the existing primary literature describing pharmacist PrEP services in the community in states with restrictive prescription authority. Methods: A systemic literature review was conducted to identify the primary literature that involved community pharmacy service …

Qualitative Investigation Of School Experiences In Children With Osteogenesis Imperfecta, Julia M Morales, Andrew D Wiese, Whitney S Shepherd, Gianna M Colombo, Selena Guo, Justin Qian, W Conor Rork, Hannah Cho, Kristin M Kostick-Quenet, Dianne Nguyen, Erin M Carter, Michelle L Fynan, Members Of The Bbdc, Chaya N Murali, Marie-Eve Robinson, Sophie C Schneider, Brendan Lee, V Reid Sutton, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Osteogenesis imperfecta (OI) is a rare genetic chronic condition leading to fragile bones and frequent bone fractures with wide-reaching health implications. Current literature suggests that children with chronic diseases face unique challenges at school, yet research regarding educational concerns among those with OI is limited. The present study involved qualitative analysis of semi-structured interviews with 10 children with OI and 12 caregivers of a child with OI. Children and caregivers participated in the interviews individually; they were not dyads of participants. Half of the caregivers who participated had OI themselves. The interviews were coded, and six themes were identified: (1) …

Olfactory Deficit And Gastrointestinal Dysfunction Precede Motor Abnormalities In Alpha-Synuclein G51d Knock-In Mice, Youngdoo Kim, Joseph Mcinnes, Jiyoen Kim, Yan Hong Wei Liang, Surabi Veeraragavan, Alexandra Rae Garza, Benjamin David Webst Belfort, Benjamin Arenkiel, Rodney Samaco, Huda Yahya Zoghbi

Faculty, Staff and Students Publications

Many Parkinson’s disease (PD) models overexpress α-Synuclein using heterologous promoters, which is adequate to demonstrate that excessive α-Synuclein is toxic but not ideal for learning the precise ontogeny of the disease pathogenesis, specifically where the disease starts and how it progresses. To answer these questions, it is beneficial to generate a mouse model expressing a disease-causing mutation under the endogenous promoter. Here, we generated three Snca knock-in mice. Among them, homozygous Snca^G51D mice develop motor deficits by 9 mo of age. These mice exhibit olfactory and gastrointestinal abnormalities by 6 mo. They lose dopaminergic neurons and have reduced dopamine …

Metadegron: Multimodal Feature-Integrated Protein Language Model For Predicting E3 Ligase Targeted Degrons, Mengqiu Zheng, Shaofeng Lin, Kunqi Chen, Ruifeng Hu, Liming Wang, Zhongming Zhao, Haodong Xu

Faculty, Staff and Student Publications

Protein degradation through the ubiquitin proteasome system at the spatial and temporal regulation is essential for many cellular processes. E3 ligases and degradation signals (degrons), the sequences they recognize in the target proteins, are key parts of the ubiquitin-mediated proteolysis, and their interactions determine the degradation specificity and maintain cellular homeostasis. To date, only a limited number of targeted degron instances have been identified, and their properties are not yet fully characterized. To tackle on this challenge, here we develop a novel deep-learning framework, namely MetaDegron, for predicting E3 ligase targeted degron by integrating the protein language model and comprehensive …

Mta-Cooperative Prmt5 Inhibitors Enhance T Cell-Mediated Antitumor Activity In Mtap-Loss Tumors, Si Chen, Jiakai Hou, Roshni Jaffery, Ashley Guerrero, Rongjie Fu, Leilei Shi, Ningbo Zheng, Ritu Bohat, Nicholas A Egan, Chengtai Yu, Sana Sharif, Yue Lu, Wei He, Shuyue Wang, Donjeta Gjuka, Everett M Stone, Pooja Anil Shah, Jordi Rodon Ahnert, Taiping Chen, Xinli Liu, Mark T Bedford, Han Xu, Weiyi Peng

Faculty, Staff and Student Publications

BACKGROUND: Hyperactivated protein arginine methyltransferases (PRMTs) are implicated in human cancers. Inhibiting tumor intrinsic PRMT5 was reported to potentiate antitumor immune responses, highlighting the possibility of combining PRMT5 inhibitors (PRMT5i) with cancer immunotherapy. However, global suppression of PRMT5 activity impairs the effector functions of immune cells. Here, we sought to identify strategies to specifically inhibit PRMT5 activity in tumor tissues and develop effective PRMT5i-based immuno-oncology (IO) combinations for cancer treatment, particularly for methylthioadenosine phosphorylase (MTAP)-loss cancer.

METHODS: Isogeneic tumor lines with and without MTAP loss were generated by CRISPR/Cas9 knockout. The effects of two PRMT5 inhibitors (GSK3326595 and MRTX1719) were …

Thrombectomy For Stroke With Large Infarct On Noncontrast Ct: The Tesla Randomized Clinical Trial, Writing Committee For The Tesla Investigators, Albert J Yoo, Osama O Zaidat, Sunil A Sheth, Ansaar T Rai, Santiago Ortega-Gutierrez, Curtis A Given, Syed F Zaidi, Ramesh Grandhi, Hugo Cuellar, Maxim Mokin, Jeffrey M Katz, Amer Alshekhlee, Muhammad A Taqi, Sameer A Ansari, Adnan H Siddiqui, Nobl Barazangi, Joey D English, Alberto Maud, Jawad Kirmani, Rishi Gupta, Dileep R Yavagal, Jason Tarpley, Dhruvil J Pandya, Marshall C Cress, Sushrut Dharmadhikari, Kaiz S Asif, Tareq Kass-Hout, Ajit S Puri, Nazli Janjua, Aniel Q Majjhoo, Aamir Badruddin, Randall C Edgell, Rakesh Khatri, Larry Morgan, Anmar Razak, Alicia Zha, Priyank Khandelwal, Nils Mueller-Kronast, Dennis J Rivet, Thomas Wolfe, Brian Snelling, Ali Sultan-Qurraie, Shao-Pow Lin, Rajkamal Khangura, Alejandro M Spiotta, Parita Bhuva, Sergio Salazar-Marioni, Eugene Lin, Abdul R Tarabishy, Edgar A Samaniego, Murali K Kolikonda, Mouhammad A Jumaa, Vivek K Reddy, Pankaj Sharma, Olvert A Berkhemer, Pieter-Jan Van Doormaal, Adriaan C G M Van Es, Wim H Van Zwam, Bart J Emmer, Ludo F Beenen, Charles B L M Majoie, Nancy Buderer, Michelle A Detry, Anna Bosse, Todd L Graves, Christina Saunders, Lucas Elijovich, Ashutosh Jadhav, Mary Patterson, Hannah Slight, Kristine Below, Sami Al Kasab, Tesla Investigators

Faculty, Staff and Student Publications

Importance: Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset.

Objective: To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset.

Design, setting, and participants: Open-label, blinded-end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at …