Digital Commons Network^™

Cannabis Stigma And Symptom Management Considerations In Cancer Survivors: A Mixed-Methods Exploration Of Patient Perspectives, Sera Levy, Salimah Meghani, Brooke Worster, Colleen Kilanowski, Danielle Smith, Amy A. Case, Rebecca L. Ashare

Department of Medical Oncology Faculty Papers

PURPOSE: This study aims to assess for indications of stigma and attitudes toward cannabis among cancer survivors (CS) who use or consider the use of cannabis.

METHODS: This study employed a convergent, parallel mixed methods design utilizing focus group and questionnaire data to assess the presence of stigma among a sample of CS (n = 23) who use (n = 10) and do not use (n = 13) cannabis to manage symptoms. CS were recruited from a multi-site observational study in the Northeast U.S. region that assesses cannabis use among oncology patients.

RESULTS: A total of 23 CS participated in …

The Efficacy And Safety Of Serratus Anterior Plane Block In Patients Undergoing Cardiac Surgery: A Systematic Review And Meta-Analysis, Xu-Bo Cui, Ming-Zhu Cui, Qiu-Ju Yang, Yang Liu, Meng-Qi Yi, Xiao-Yang Zhang, Yun-Tai Yao

Faculty, Staff and Student Publications

Background: Serratus anterior plane block (SAPB) is a widely used fascial block that reduces postoperative pain and perioperative opioid consumption. This meta-analysis assessed the efficacy and safety of SAPB in cardiac surgery patients.

Methods: We systematically searched PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang databases on May 10, 2024. Pooled relative risks and mean differences (MD) with 95% confidence intervals (CI) were calculated for dichotomous and continuous outcomes, respectively. Heterogeneity was assessed using the I2 statistic, and publication bias was evaluated using Egger test. Subgroup analyses were stratified by study design (randomized controlled trials …

Persistent Microglial Activation Following Neonatal Cmv Infection Mediates Neurodegeneration, Jessica L. Mccord, Debotri Chatterjee, John Y.S. Han, Drew Scoles, Richard J. Smeyne, Nancy J. Philp, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Human cytomegalovirus (HCMV) causes the most common congenital viral infection in the United States, with well-known acute and late-onset neurological pathologies. Moreover, HCMV, like multiple herpesviruses, has been associated with neuroinflammation and neurodegeneration. Using a well-established neonatal murine (M)CMV infection model, we found that early-life infection drove adult-onset neuron loss and neuropathology in the retina and brain, without evident viral reactivation. Pathology was associated with the persistence of highly activated and inflammatory damage-associated microglia. Transient depletion of these microglia before the development of pathology resulted in repopulation of the tissue by microglia with a more reparative profile, which was then …

Gut Microbiota Modulation Via Repeated Donor Fecal Transplantation Improves Motor And Gastrointestinal Symptoms In Drug-Naïve Parkinson’S Disease: A Randomized Phase 2 Trial, Rui Zhang, Renyi Feng, Jiuqi Wang, Yongkang Chen, Han Liu, Qingyong Zhu, Haiyan Tian, Chi Qin, Junfang Teng, Beisha Tang, Min Wu, Jinsheng Zeng, Erxi Wu, Xuebing Ding, Xuejing Wang

Faculty, Staff and Students Publications

The gut-brain axis is increasingly recognized as a critical contributor to Parkinson's disease (PD) pathogenesis, yet the therapeutic impact of microbiota modulation remains unclear due to lack of clinical trials in drug-naïve patients. We conducted a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the safety, tolerability, and efficacy of repeated donor fecal microbiota transplantation (dFMT) in de novo PD. FMT was administered for seven days (200 mL on days 1-3; 50 mL on days 4-7) per 4-week cycle. Seventy-two patients were randomized 1:1 to receive dFMT or autologous FMT (aFMT), and 66 completed the trial. At 35 weeks, the …

Publication Productivity Among International Medical Graduates And U.S. Medical Graduates In Neurosurgery: A Comparative Assessment Using The Arms Race Control Score, Joanna M. Roy, Omar M. M. Mansoor, Samit Sen, Aaron C. Segura, Rithvik Naga Ganti, Basel Musmar, Gilberto Perez Rodriguez Garcia, Brett Henshey, Saarang Patel, Sruthi Ranganathan, Victor Gabriel El-Hajj, Stavropoula I. Tjoumakaris, M. Reid Gooch, Robert H. Rosenwasswer, Christian Bowers, Pascal Jabbour

Department of Neurosurgery Faculty Papers

BACKGROUND AND OBJECTIVES: The Arms Race Control Score (ARCS) was developed to provide a quantitative assessment of publications among residency applicants. International medical graduates (IMGs) often have higher numbers of publications compared to U.S medical graduates (US MDs). However, there is limited knowledge of publication quality and effort among IMGs and US MDs. Our study analyzes publication productivity among IMGs and US MDs using the ARCS.

METHODS: Applicants were selected from ACGME-accredited training programs that enrolled both IMG and US MD residents over the 2018-2024 match cycle. Programs without IMG residents in a given year were excluded from the analysis. …

Mist: A Hierarchical Bayesian Framework For Detecting Differential Dna Methylation Dynamics In Single-Cell Data, Daoyu Duan, Wenjing Ma, Wen Tang, Hao Wu, Liangliang Zhang, Hao Feng

Faculty, Staff and Student Publications

Recent advancements in single-cell DNA methylation (scDNAm) sequencing technologies have enabled the profiling of epigenetic landscapes at unprecedented resolution, offering insights into cellular heterogeneity, differentiation and evolution. Trajectory inference, which orders cells along pseudotime, allows researchers to track genomics changes across continuous cell states and identify key loci exhibiting differential methylation. However, no methods currently exist to model methylation changes along pseudotime in scDNAm data. Here, we present a hierarchical Bayesian framework for scDNAm data analysis. Our method, named mist (methylation inference for single-cell along trajectory), models stage-specific biological variations, identifies genomic features with significant methylation changes along pseudotime, and …

Cost-Effectiveness And Implementation Strategies For Hypertension Management Using Non-Physician Healthcare Workers In Low- And Middle-Income Countries: A Systematic Review, Gabriel Lamkur Shedul, Olutobi Adekunle Sanuade, Emmanuel Iroboudu Okpetu, Molly Beestrum, Dike Bevis Ojji, Lisa R Hirschhorn, Mark D Huffman, Dustin D French

2020-Current year OA Pubs

BACKGROUND: This review assessed the cost-effectiveness and implementation strategies of hypertension management by non-physician healthcare workers (NPHCWs) in low- and middle-income countries (LMICs).

METHODS: A systematic search (inception-May 2024) included adults ≥18 years managed by NPHCWs LMICs, following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Economic evaluations were assessed using Drummond's checklist and ROBINS-I.

RESULTS: Seven studies (2002-2022) conducted across eight countries enrolled 96-10,000 participants and included randomized, modeling, observational, and quasi-experimental designs. NPHCWs included pharmacists, community and village health workers, and nurses. Patients' mean age ranged 58-71 years, with 57-82% female. Outcomes assessed included cost per …

The Use And Utility Of Wearable Devices For Tracking Sleep And Activity In Inpatient Mental Health Settings: Protocol For A Rapid Review, Gillian Strudwick, Hwayeon Danielle Shin, Iman Kassam, Karishini Ramamoorthi, Benjamin Rosen, Michelle A Patriquin, Justin Baker, Nicholas Neufeld

Faculty, Staff and Student Publications

Background: Wearable devices offer an opportunity to objectively monitor and capture sleep and activity in psychiatric inpatient settings, where traditional approaches often rely on subjective reporting or staff observation, both of which have inherent flaws. Technologies such as Fitbit, Garmin, Oura Ring, GENEActiv, Empatica, and WHOOP (among others) have been used to passively collect physiological data that may inform care planning and clinical decision-making. Despite growing interest, the extent to which these wearables are feasible, acceptable, and useful in inpatient mental health settings remains unclear. Synthesizing this evidence is essential to inform their potential integration into psychiatric care.

Objective: This …

Clinical Trial Success Rate In Lymphoma: Fate Of Trials And Agents From 2000 To 2019, Zhiping Luo, Meng Li, Brian C Primeaux, Rahul Shah, Ruitao Lin, Swaminathan P Iyer, Loretta J Nastoupil, Michael R Green, Jason R Westin, Christopher R Flowers, Dai Chihara

Faculty, Staff and Student Publications

Although previous studies have examined the drug development and clinical trial success rates in oncology, a comprehensive analysis of development success rate in lymphoma has not been performed. Therefore, we analyzed lymphoma trials initiated between 1 January 2000 and 31 December 2019, using the Trialtrove database and ClinicalTrials.gov. We identified phase 1, 2, and 3 trials that included patients with lymphoma and analyzed the transition rate of investigational agents across phases and their US Food and Drug Administration (FDA) approval rates to assess the efficiency and success of the clinical development process. A total of 1032 phase 1 trials and …

International Consensus-Driven Recommendations For Patient-Reported Outcome Research Objectives In Early Phase Dose-Finding Oncology Trials: Optimise-Ror, Emily Alger, Olalekan Lee Aiyegbusi, Amylou C Dueck, Anna Minchom, Madeline Pe, John D Peipert, Claire Snyder, Stefan N Symeonides, Roger Wilson, Ethan Basch, Yu Qiao, Susan E Bates, Helen Bulbeck, Lizzie Dean, Massimo Di Maio, Aaron R Hansen, Olga Kholmanskikh, Ken Kobayashi, Dónal Landers, Christophe Le Tourneau, J Jack Lee, Brigette B Y Ma, Lynley V Marshall, Sheetal Patel, Joan Petrie, Gregory R Pond, Kieran Prior, Khadija R Rantell, John F Reeve, Olga Solovyeva, Nolan A Wages, Harald A Weber, Melanie J Calvert, Christina Yap

Faculty, Staff and Student Publications

Purpose: There is growing scientific interest in incorporating patient-reported outcomes (PROs) in early phase dose-finding oncology trials (DFOTs) to assess tolerability, inform dose selection, and guide later stage trial design. However, research indicates that PRO objectives in DFOTs are often unclear. The Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Research Objectives Recommendations (OPTIMISE-ROR) project was established to support trialists to effectively incorporate PROs into DFOTs.

Methods: Using the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework, guideline development included the following: (1) a methodological review of published DFOTs incorporating PROs; (2) candidate item generation, refined through expert consultation; (3) …

Virtual Reality For The Management Of Postoperative Pain And Anxiety In Children And Adolescents Undergoing Nuss Repair Of Pectus Excavatum: Randomized Controlled Trial, Charlotte M. Walter, Dillon Froass, Nora Bell, Lauren Haack, Chloe Boehmer, Claudia Bruguera Torres, Rachel Spivak, Max Chou, Kristie Geisler, Keith O'Conor, Sara E. Williams, Lili Ding, Christopher D. King, Vanessa A. Olbrecht

Department of Medicine Faculty Papers

BACKGROUND: Virtual reality (VR) is a novel technology with implications for pain and sensory processing. VR may serve as a novel, scalable method to deliver clinically validated therapy for pain management as an alternative or adjunct to opioids for acute pain. Given that psychological factors and pain perception are both components of postoperative pain, it may also be beneficial to incorporate modalities that decrease anxiety, such as active relaxation and guided meditation with VR. Unfortunately, these therapies are not widely available due to multiple barriers. VR has the potential to deliver pain-reducing, psychologically based therapy to children, thereby enhancing multimodal …

Hematopoietic Cell Transplantation For Wiskott-Aldrich Syndrome: A Pidtc Report, Jessie L Alexander, Blachy J Dávila Saldaña, Ruta Brazauskas, Sravya Gethika Dammalapati, Linda M Griffith, Ami J Shah, Kristin A Shimano, Hans D Ochs, Jack J Bleesing, Christen L Ebens, Malika Kapadia, Andrea Bauchat, Neena Kapoor, Joseph H Oved, Hesham Eissa, Hannah Lust, Michael D Keller, Hilary Haines, Shanmuganathan Chandrakasan, Julie-An Talano, Ahmad Rayes, Lisa Madden, Evan Shereck, Holly K Miller, Lisa Forbes Satter, Caridad Martinez, Jacob Rozmus, Jeffrey J Bednarski, Lolie C Yu, Deepakbabu Chellapandian, Victor M Aquino, Alan Knutsen, Hey Chong, Ashley Chopek, Alfred P Gillio, Avni Joshi, Hemalatha Rangarajan, Theodore B Moore, Jeffrey R Andolina, Kenneth B Desantes, Mark Vander Lugt, Susan E Prockop, David C Shyr, Kathleen E Sullivan, Suhag Parikh, Katja G Weinacht, Troy R Torgerson, Rebecca Marsh, Christopher C Dvorak, Alice Y Chan, Elie Haddad, Jennifer R Heimall, Michael A Pulsipher, Jennifer W Leiding, Donald B Kohn, Jennifer M Puck, Luigi D Notarangelo, David J Rawlings, Morton J Cowan, Aleksandra Petrovic, Sung-Yun Pai, Lauri M Burroughs

Faculty, Staff and Students Publications

Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to affect overall survival (OS). However, the influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium from 1990 to 2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and …

Bacterial Fecal Microbiome Composition Associated With Hiv Stage Among Rural And Peri-Urban Adults Living With Hiv In Uganda, Bożena M Morawski, Elise R Morton, Miya Yunus, Claudia Muñoz-Zanzi, Rojelio Mejia, Ran Blekhman, David R Boulware, Sarah M Lofgren

Faculty, Staff and Students Publications

Background

Gut microbiome composition in HIV-infection provides insight into HIV pathogenesis and potentially offers avenues to adjunctive HIV therapies. Although two-thirds of people living with HIV (PLHIV) are in Africa, studies of the gut microbiome PLHIV have focused on non-African populations. Additionally, social, cultural, and environmental factors influence the gut microbiome and differ substantially between African and Western and urban and rural communities. Here, we quantify the relationships between immune status and fecal microbiome composition in 175 rural Ugandan PLHIV.

Methods

In 2013, 175 Ugandan PLHIV contributed a single fecal sample as part of a cohort study of 202 participants. …

Underexplored Maternal Microbiomes: Immune, Metabolic, And Microbial Pathways Shaping Pregnancy Outcomes, Rafael Tomoya Michita, Nicole Jimenez, Melissa M Herbst-Kralovetz, Indira U Mysorekar

Faculty, Staff and Students Publications

Maternal microbial ecosystems play critical roles in shaping reproductive physiology and pregnancy outcomes. During the pre-conception and prenatal periods, these communities modulate maternal physiology by regulating immune tolerance, nutrient metabolism, and susceptibility to pregnancy complications such as preterm birth, hypertensive disorders, and gestational diabetes. While the gut microbiota has been extensively studied, the roles of cervicovaginal, urinary, respiratory, oral, and upper reproductive tract microbiomes remain less clear. In this minireview, we synthesize current knowledge on these underexplored maternal microbiomes, with an emphasis on the cervicovaginal and urinary microbiota and their interactions with the placenta and fetus. We discuss cross-niche microbial …

Incarcerated Geriatric Patients’ Experiences Of Aging And Healthcare, Michelle I Suh, Stephen Chen, Megan Benavides, Sumin Yoon, Nia Lucas, Josiah D Rich, Marc David Robinson, Anita N Chary

Faculty, Staff and Students Publications

Older adults comprise the fastest growing demographic in correctional facilities in the United States. Studies have shown older adults in prison report difficulty accessing healthcare and navigating the prison environment. Little is known about how older adults navigate aging and access healthcare in the jail setting. We sought to explore experiences of older adults incarcerated in a county jail. We conducted semi-structured qualitative interviews with 20 older adults (> 50 years old) who were incarcerated at a local county jail and were referred to the emergency department for acute care needs. Interviews focused on experiences of aging while incarcerated and …

Emapalumab Use In Malignancy-Associated Hemophagocytic Lymphohistiocytosis In The United States: The Real-Hlh Study, Adi Zoref-Lorenz, Carl E Allen, Edward M Behrens, Shanmuganathan Chandrakasan, May Chien, Michelle L Hermiston, Ashley P Hinson, Stefanos Intzes, Michael S Isakoff, Jennifer W Leiding, Abiola Oladapo, Arun Panigrahi, Sachit A Patel, Priti Pednekar, Anish K Ray, Jennifer A Rothman, Blachy Dávila Saldaña, Kelly J Walkovich, Joanna Weinstein, John D Yee, Michael B Jordan, Joanna Weinstein, Ashley P Hinson, Carl E Allen, Olive S Eckstein, Nitya Gulati, Shanmuganathan Chandrakasan, Hilary Haines, Taizo A Nakano, Sachit A Patel, Edward M Behrens, Stefanos Intzes, Allyson Hays, Blachy Dávila Saldaña, Michael B Jordan, Adi Zoref-Lorenz, Rabi Hanna, Michael Isakoff, Anish K Ray, Jennifer A Rothman, Anand Tandra, Robert Cooper, Jennifer W Leiding, May Chien, Susmita Sarangi, Vinod K Gidvani-Diaz, Prakash Satwani, John Carter, Michael Henry, Nicholas Gloude, Sima Bhatt, Deepika Bhatla, Lauren Draper, Arun Panigrahi, Michelle L Hermiston, Renee Modica, Mona Riskalla, Ashley Baker, Brant Ward

Faculty, Staff and Students Publications

Malignancy-associated hemophagocytic lymphohistiocytosis (mHLH), a hyperinflammatory syndrome, has poor prognosis and no standard therapy. Emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon gamma, is approved for treating primary hemophagocytic lymphohistiocytosis (pHLH). REAL-HLH, a retrospective chart review conducted across 33 US hospitals, evaluated real-world treatment patterns and outcomes in patients treated with ≥1 dose of emapalumab between 20 November 2018 and 31 October 2021. Data are presented for the subset of patients with mHLH. Overall, 51 of 105 (48.6%) patients were categorized as having secondary HLH, of which 17 of 51 patients had HLH associated with an …

A Case Of Autosomal Dominant Polycystic Kidney Disease With Multiple Bilateral Spontaneous Retroperitoneal Hemorrhages, Masato Mizuta, Tatsuya Suwabe, Yuki Oba, Akinari Sekine, Masayuki Yamanouchi, Hiroki Mizuno, Eiko Hasegawa, Takehiko Wada, Makoto Fukuda, Motoaki Miyazono, Naoki Sawa, Yoshifumi Ubara

Children’s Nutrition Research Center Staff Publications

We experienced a 45-year-old male with ADPKD who developed spontaneous retroperitoneal hemorrhages with hypertension in the right subcapsular renal space without trauma. After his condition worsened with conservative management, he was treated by renal transarterial embolization (TAE). Over the next eight years, he experienced bilateral bleeding at three different sites and underwent repeated endovascular treatment with renal TAE to stop the bleeding. After the fourth occurrence, the patient underwent hemodialysis. Although renal cysts and urinary tract bleeding occur frequently in ADPKD, retroperitoneal hemorrhage is rare; however, TAE is both effective and a good way to preserve renal function.

Penile Prosthetic Infections: What Can Be Learned From Orthopedics?, Kenneth B Mathis, Alisina Shahi

Faculty, Staff and Student Publications

No abstract provided.

Kinetic Human Movement Ontology: A Semantic Terminology Model To Symbolically Represent Physiological Movement, Muhammad Amith, Vivian Ha, Eloisa Nguyen, Yang Gong, Ahsiya Lin, Cui Tao, Licong Cui

Faculty, Staff and Student Publications

Cataloging physiological and anatomical terminologies may provide a fundamental basis for bridging the involvement of muscles, skeletal, and other essential parts in human movement, in addition to understanding their role on human morbidity. We present a general formalized ontology model that focuses on anatomical and physiological entities that are active during human movement, called the Kinetic Human Movement Ontology (KHMO). We developed a model to represent human movement that links human postures using OWL2. We used the model to assemble various open-sourced controlled terminologies involved in human movement - anatomical entities, physiological terms, etc. KHMO presents 1954 classes, 42 properties, …

Multi-Stakeholder Perspectives On Barriers To Mental Health Support For Informal Caregivers, Maria Lizette Rangel, Donaji Stelzig, Cassandra Martinez Enriquez, Hoda Badr

Department of Medical Oncology Faculty Papers

BACKGROUND: Informal caregivers experience elevated psychological distress but face substantial challenges in accessing mental health support. Prior research has focused primarily on individual or interpersonal determinants, with less attention to how organizational, community, and policy contexts shape access and contribute to inequities in service availability.

METHODS: Fifty-one stakeholders, including 17 informal caregivers, 23 community health workers (CHWs), and 11 mental health professionals, completed a demographic survey and 60-90-min semi-structured interviews in English or Spanish. Data were analyzed using thematic analysis, combining deductive coding guided by the Socioecological Model with inductive identification of emergent themes.

RESULTS: Participants identified both barriers and …

Development Of A Sustainable Blended Food Aid Product Using Local Ingredients For Nutritionally Vulnerable Populations In Haiti, Sherlie Jean Louis Dulience, Rachel Zimmerman, Michelle Dorce, Ilana Seff, Andrea Spray Bulungu, Patricia Kohl, Carolyn Lesorogol, Bazelais Dulience, Lora Iannotti

2020-Current year OA Pubs

OBJECTIVES: This study aimed to: (1) identify optimal blended food recipe options using local flours; (2) assess behaviors, attitudes, and practices around the use of blended foods among nutritionally vulnerable groups in Haiti; and (3) evaluate the nutrient composition of prototype blended food product relative to nutrient requirements for vulnerable populations.

METHODS: Blended food recipes made from local flours were identified through matrix scoring and stakeholder consensus. Focus groups (n = 7) assessed behaviors and attitudes toward blended foods. Prototype recipes were selected based on matrix scoring, program participant feedback, and feasibility of bringing to scale. Nutrient composition of the …

Identification Of De Novo Variants From Parent-Proband Duos Via Long-Read Sequencing, Leandros Boukas, Emmanuèle C. Délot, Georgia Pitsava, Christine Lambert, Cairbre Fanslow, Primo Baybayan, Sami Belhadj, Bojan Losic, John Harting, Krista Bluske, Jonathan Lotempio, Huda B. Al-Kouatly, Rachid Karam, William J. Rowell, Changrui Xiao, Eric Vilain, Seth I. Berger

Department of Obstetrics and Gynecology Faculty Papers

While de novo variants cause many Mendelian disorders, their detection currently requires sequencing of the proband and both biological parents. This is not feasible when only one parent is available, a limitation for millions of families. Here, we develop duoNovo, which identifies de novo variants from parent-proband duos using long-read sequencing followed by haplotype reconstruction and detection of identical-by-descent haplotype blocks. We sequenced 104 trios with PacBio HiFi sequencing and applied duoNovo to each of the 208 duos constructed by masking one parent, classifying over 55 million variants according to their de novo status. We evaluated duoNovo's performance against classifications …

Immune-Mediated Necrotising Myopathy Following Semaglutide Treatment: A Contributing Factor?, Brian Lam, Eleni Tiniakou, Xinhai Robert Zhang, Shervin Assassi

Faculty, Staff and Student Publications

This report describes a female patient in her 60s with an immune-mediated necrotising myopathy (IMNM) occurring after semaglutide use. She was found to have progressive dysphagia, dysphonia, proximal muscle weakness and creatine kinase elevation over a 4-month course. Her symptoms were preceded by a single dose of semaglutide. Her work-up revealed features consistent with necrotising myopathy with inflammatory infiltrate on biopsy, and she responded to immunosuppression with corticosteroids and intravenous immunoglobulin (IVIG). She gradually improved and successfully returned to her baseline functional status while off immunosuppression for several months and with continued avoidance of glucagon-like peptide-1 (GLP-1) receptor agonists. Here, …

Bi-Allelic Variants In Nrdc Cause A Neurodevelopmental Disorder Characterized By Neonatal Lethality, Microcephaly, And Brain Abnormalities, Davut Pehlivan, Abigail Sandoval, Reza Maroofian, François Lecoquierre, Aisha M Al Shamsi, Gyu S Lee, Osman Yesilbas, Preston Taylor, Matthew B Mcdougal, Vahid Bahrambeigi, Omid Aryani, Juan Felipe Ramirez, Khalid Hama Salih, Chadi Al Alam, Heba Morsy, Haytham Hussien, Tarek Omar, Ibrahim M Abdelrazek, Anne Claire Brehin, Dana Marafi, Tugba Kalayci, Jubran Abu Rahma, Jawabreh Kassem Talbeya, Husein Dabbah, Eric Verspyck, Toktam Moosavian, Jawid M Fatih, Tadahiro Mitani, Gulsen Akay, Daniel G Calame, Anne-Marie Guerrot, Wendy K Chung, Henry Houlden, James R Lupski, Adel Shalata, Wan Hee Yoon

Faculty, Staff and Students Publications

Nardilysin (NRDC) plays a role in multiple cellular functions in diverse cellular compartments, including ectodomain shedding in the plasma membrane, as well as chaperoning a key Krebs cycle enzyme in mitochondria. We had previously reported limited clinical information from two individuals with homozygous frameshift variants in NRDC. With inclusion of previously published individuals, here we report 14 individuals (10 females, four males) from nine unrelated families carrying homozygous NRDC pathogenic variants. Common clinical features include severe to profound developmental delay/intellectual disability (12/12), microcephaly (13/13), prematurity (5/13), lethality in the first 3 years of life (9/14), seizures (7/11), joint contractures (4/8), …

Proteomics Analysis Of Plasma For Risk Of Sepsis: Findings From The Atherosclerosis Risk In Communities Study, Junichi Ishigami, Xiao Hu, Pascal Schlosser, Thomas R Austin, Jingsha Chen, Bruce M Psaty, David Dowdy, Christie M Ballantyne, Morgan E Grams, Josef Coresh, James S Floyd, Kunihiro Matsushita

Faculty, Staff and Students Publications

Background: Sepsis is a life-threatening complication of infection with high mortality. A high-throughput analysis of circulating blood proteins may provide mechanistic insight and potent therapeutic targets for the prevention of sepsis.

Methods: We used multivariable Cox regression analysis to examine the association of 4955 plasma proteins, measured by SomaScan, with the risk of incident sepsis among 11 065 participants of the Atherosclerosis Risk in Communities (ARIC) Study (visit 3 in 1993 to 1995; mean age, 60.1 years, 54.4% female, 21.0% Black). Proteins (false discovery rate [FDR] of P < 0.05) discovered at visit 3 were replicated using data at visit 5 (n = 4869 in 2011 to 2013: mean age, 75.5 years) and in the Cardiovascular Health Study (CHS) (n = 3512 in 1992 to 1993; mean age, 74.5 years). Canonical pathways were identified by enrichment analyses.

Results: At ARIC visit three, 669 proteins were associated with the risk …

Smartphone-Based Ecological Momentary Assessment Of Pain In Older Adults Undergoing Auricular Point Acupressure For Chronic Low Back Pain: Secondary Analysis Of A Randomized Controlled Trial, Nada Lukkahatai, Chitchanok Benjasirisan, Xinran Huang, Hulin Wu, Jennifer Kawi, Jingyu Zhang, Claudia M Campbell, Constance M Johnson, Paul J Christo, Johannes Thrul

Faculty, Staff and Student Publications

Background: Chronic low back pain (cLBP) is a prevalent and disabling condition in older adults. Auricular point acupressure (APA), a nonpharmacologic intervention, has shown promise in managing cLBP. However, its impact on daily symptom fluctuations remains unclear. Ecological momentary assessment (EMA), which collects real-time data, offers a method to capture these fluctuations.

Objective: This secondary analysis evaluated the effects of APA on EMA-reported pain intensity and pain interference among older adults with cLBP and examined associations among APA practice patterns, recall-based assessments, and EMA engagement.

Methods: Data were drawn from a published 3-arm randomized controlled trial of 272 adults aged …

Sickle Cell Visualization In Vivo In Humans: Microvascular Occlusion Formation And Hemorheological Indices, Marisa M Morakis, Luojie Huang, Gregory N. Mckay, Sophie Lanzkron, Lydia H. Pecker, Nicholas J. Durr

Cardeza Foundation for Hematologic Research

Vaso-occlusion is a signature pathology of sickle cell disease (SCD). However, the lack of in vivo methods to observe individual blood cell dynamics in humans limits our understanding of occlusion formation mechanisms. We present a novel in vivo, noninvasive, label-free, and high-resolution imaging technique to study blood flow and sickled cell behavior in affected individuals. We used oblique back-illumination microscopy (OBM) to capture videos of 91.0 ± 42.3 sublingual capillaries in each of 10 participants with SCD before and after red cell transfusions and compared the measurements to 10 unaffected controls. With direct observation of blood cell activity, we identified …

Medial Pulvinar Nucleus As A Causal Hub For Heteromodal Naming, Oscar Woolnough, Tessy Thomas, Kathryn M Snyder, Ellery Wheeler, Jay Gavvala, Nitin Tandon

Faculty, Staff and Student Publications

Our ability to retrieve the names of objects in our environment is a fundamental aspect of everyday life. This process requires a complex, dynamic network of cortical and subcortical interactions. While the cortical constituents of this network have been extensively studied with intracranial recordings, the subcortical nodes of the naming network are unclear. We probed the role of the left medial pulvinar nucleus in naming with direct intracranial recordings and stimulation in eight humans (three male, five female) as they named objects using pictures and auditory and written descriptions. We found a spectrotemporal signature of naming in the left medial …

Modulating Alternative Splicing Of Mecp2 Is A Potential Therapeutic Strategy For Rett Syndrome, Harini P Tirumala, Li Wang, Yan Li, Sameer S Bajikar, Ashley G Anderson, Wei Wang, Alexander J Trostle, Mahla Zahabiyon, Aleksandar Bajic, Jean J Kim, Hu Chen, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Rett syndrome (RTT) is a neurological disorder caused by loss-of-function mutations in methyl CpG binding protein 2 (MECP2), a transcriptional regulator essential for maintenance of normal neuronal function. The current FDA-approved treatment for RTT, Trofinetide, mildly alleviates some symptoms. In contrast, re-introducing MeCP2 or increasing its amount through transgenesis in mouse RTT models improves most neurological phenotypes and enhances survival. Here, we devised a therapeutic strategy to moderately increase MeCP2 protein by modulating the alternative splicing of MECP2 to switch the less efficiently translated e2 to the more efficiently translated e1 isoform. We deleted Mecp2 exon 2 (unique …

Post-Traumatic Stress Disorder And Risk Of All-Cause And Cause-Specific Mortality: A Nationwide Population And Sibling-Controlled Cohort Study In Taiwan, Chih-Wei Hsu, 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

Aims: Post-traumatic stress disorder (PTSD) may shorten life expectancy, but evidence for Asian populations and cause-specific mortality remains limited. The aim of this study is to investigate the association between PTSD and mortality risk in an Asian population.

Methods: We used Taiwan's National Health Insurance Research Database (2000-2022) to assemble a cohort of 28,777 individuals with incident PTSD and 115,108 age- and sex-matched unexposed individuals, plus a sibling cohort of 13,305 affected patients and 22,030 unaffected siblings. Cox models estimated adjusted hazard ratios (AHRs) for all-cause, unnatural-cause (suicide and accidents) and natural-cause mortality, with progressive adjustment for sociodemographic factors, comorbidity …