Digital Commons Network^™

Wavelet-Based Mechanomyographic Intensity Responses To Sustained Tasks Anchored To Low Versus High Ratings Of Perceived Exertion, Dolores G. Ortega, Robert W. Smith, Jocelyn E. Arnett, Tyler J. Neltner, Trevor D. Roberts, Justin S. Pioske, Richard J. Schmidt, Terry J. Housh

Journal for Sports Neuroscience

Purpose: This study examined the effects of sustained, isometric forearm flexion tasks anchored to ratings of perceived exertion of 2 (RPE2_FT) versus 8 (RPE8_FT) on the wavelet-based mechanomyographic (MMG) intensity responses from pretest and posttest maximal voluntary isometric contractions (MVICs) as well as the time course of changes in the MMG intensity responses throughout the sustained tasks. Methods: Eleven men (mean±SD: age=20.9±2.3 yrs) performed MVICs before and after the sustained tasks. The wavelet analyses decomposed the MMG signals onto a set of 11 wavelet bands (WBs). Repeated measures ANOVAs were used to analyze the MMG intensity …

Global Deep-Sea Hydrothermal Deposit Metagenomes And Metagenome-Assembled Genomes Over Time And Space, Emily St John, Anna-Louise Reysenbach

Center for Life in Extreme Environments Publications

Actively venting high temperature deep-sea hydrothermal vent deposits along tectonic spreading centers and in backarc basins harbor a rich diversity of thermophilic Bacteria and Archaea, many of which have no representatives in cultivation nor any genomic representation in databases. Here, in order to produce a global-scale time series metagenomic resource for studying the microbial functional and genomic diversity in these high temperature ecosystems, we obtained 70 metagenomes from collections across spatial and temporal gradients from 21 different vent fields spanning 16 years (1993-2009). The dataset (Deep-Sea Hydrothermal Vent dataset (DSV70)) includes 3.56 Tbp of raw DNA sequence reads, that have …

Evaluating The Fate And Variability Of Soil Organic Carbon And Nitrogen Species Under Conservation Practices In The Raccoon River Watershed, Zhonglong Zhang, May Wu

Civil and Environmental Engineering Faculty Publications and Presentations

This study evaluates the fate and variability of soil organic carbon (SOC) stocks and nitrogen species using the latest version of the Soil and Water Assessment Tool– Carbon (SWAT-C) and assesses how conservation practices influence their dynamics in the Raccoon River Watershed (RRW). Dominated by intensive agricultural pro- duction, the RRW is a significant contributor of sediment and nutrient loads to local rivers and the Mississippi River. This SWAT-C model simulates the export of SOC and nitrogen species and evaluates their responses under varying management scenarios. Model calibration was performed for streamflow, sediment, nitrate, total nitrogen, and organic carbon with …

An Inflammatory And Quiescent Hsc Subpopulation Expands With Age In Humans., Ksenia R Safina, Basit Salik, Dylan Kotliar, Michelle Curtis, Jonathan D Good, Chen Weng, Shawn David, Soumya Raychaudhuri, Antonia Kreso, Jennifer J. Trowbridge, Vijay G Sankaran, Peter Van Galen

Faculty Research 2026

Aging of the blood system impacts systemic health and can be traced to hematopoietic stem cells (HSCs). Despite multiple reports on human HSC aging, a unified map detailing their molecular age-related changes is lacking. We developed a consensus map of gene expression in HSCs by integrating seven single-cell datasets. This map reveals previously unappreciated heterogeneity within the HSC population. It also links inflammatory pathway activation (TNF/NFκB, AP-1) and quiescence within a single gene expression program. This program dominates an inflammatory HSC subpopulation that increases with age, highlighting a potential target for further experimental studies and anti-aging interventions.

Theoretical Analysis Of Mir-Based Differential Photoacoustic Spectroscopy For Noninvasive Glucose Sensing, Tasnim Ahmed, Khan Mahmud, Md Rejvi Kaysir, Shazzad Rassel, Dayan Ban

Electrical and Computer Engineering Faculty Research

Diabetes is a developing global health concern that cannot be cured, necessitating frequent blood glucose monitoring and dietary management. Photoacoustic Spectroscopy (PAS) in the mid-infrared (MIR) region has recently emerged as a viable noninvasive blood glucose monitoring technique. However, MIR-PAS confronts significant challenges: (i) Water absorption, which reduces light penetration, and (ii) interference from other blood components. This paper systematically analyzes the background of photoacoustic signal generation and proposes a differential PAS (DPAS) in the MIR region for removing the background signals arising from water and other interfering components of blood, which improves the overall detection sensitivity. A detailed mathematical …

An Inflammatory And Quiescent Hsc Subpopulation Expands With Age In Humans., Ksenia R Safina, Basit Salik, Dylan Kotliar, Michelle Curtis, Jonathan D Good, Chen Weng, Shawn David, Soumya Raychaudhuri, Antonia Kreso, Jennifer J. Trowbridge, Vijay G Sankaran, Peter Van Galen

Faculty Research 2026

Aging of the blood system impacts systemic health and can be traced to hematopoietic stem cells (HSCs). Despite multiple reports on human HSC aging, a unified map detailing their molecular age-related changes is lacking. We developed a consensus map of gene expression in HSCs by integrating seven single-cell datasets. This map reveals previously unappreciated heterogeneity within the HSC population. It also links inflammatory pathway activation (TNF/NFκB, AP-1) and quiescence within a single gene expression program. This program dominates an inflammatory HSC subpopulation that increases with age, highlighting a potential target for further experimental studies and anti-aging interventions.

A Deep Learning-Based Real-Time No-Reference Image Decolorization Network With Perceptual Preservation, Mengjuan Zhao, Yitao Liang, Weiya Shi, Juan Xia

Turkish Journal of Electrical Engineering and Computer Sciences

Currently, grayscale images are preferred as input data for some specific vision tasks. Decolorization is the transformation of a color image into a grayscale image. Efficient decolorization algorithms can improve the overall task efficiency, while perceptual preservation in decolorization can provide more information for further processing. In recent research, traditional methods focus on preserving contrast or detail information with little attention to perceptual features. Deep-learning methods are beginning to consider perceptual preservation, but they run inefficiently. In addition, the decolorization methods lack the optimal target grayscale images for reference. Therefore, we propose a new deep learning-based real-time no-reference decolorization network …

Volume Cxlv, Number 9, January 16, 2026, Lawrence University

The Lawrentian

No abstract provided.

Ai Derivation And Exploration Of Antibiotic Class Spaces, Adam Bess, Sean Rowland, Chris Alvin, Supratik Mukhopadhyay

Open Access Fund Publications

Purpose The rapid evolution of antibiotic-resistant bacteria poses an urgent global health crisis. A key gap in current antibiotic discovery approaches is the absence of automated chemical synthesis methods designed to systematically generate and evaluate compounds within specific antibiotic classes. We address this gap through fragment-based computational experiments that systematically explore antibiotic chemical spaces.

Methods Our computational methodology consists of three steps: fragmentation of known compounds (eMolFrag), generating new molecular structures by recombining fragments (eSynth), and filtering of candidates based on desired properties (eFilter). eFilter combines structural analysis, pathway information, and protein targets …

Fda's New Approval Plan For Covid-19 Vaccines: An Inquiry Of "Benefit" Rather Than The Statutory Scope Of "Safety, Purity, And Potency"?, Henry Yat-Shing Kwan

Journal of Law and Health

This article analyzes the FDA's proposed policy plan issued in May 2025 regarding the approval of Covid-19 boosters for different groups of persons. It offers two constructive recommendations that will help prevent constitutionality challenge on impermissible intrusion of the freedom of health.

The first is to avoid using the confusing term "benefit" but instead focus on the statutory parameters of "safety, purity, and potency." The affected group can make a strong case that their free choice of vaccination should not be deprived, as long as the vaccine qualifies for the statutory thresholds of being safe, pure, and potent. They are …

Patent Pending: How The Current Patent Utility Requirement Hinders Biotechnological Innovation, Madison Drlik

Journal of Law and Health

The legal system is always playing catch up to adapt to new legal landscapes, doctrines, and technology; however, patent law needs help to compete with biotechnological research in the race towards innovation. Biotechnological research in the realm of human health and medicine often involves the use of therapeutic drugs. The field of healthcare biotechnology takes biological systems and processes and generates novel, creative solutions to a number of human health conditions. However, the translation process for a new drug, therapy, or process is long and expensive which requires investors to help the researchers and scientists move their creations from inception …

Explaining Transformer-Based Classification Of Radiology Reports, M Courtman, G Abdelhalim, L Sun, E Ifeachor, S Mullin, M Thurston

Peninsula Medical School

ObjectivesDeep learning models developed for the classification of radiological reports have lacked explainability. We aimed to validate and explain a pretrained classification model by applying it to the removal of confounding data from a radiological dataset.MethodsTwo radiologists categorized 2038 anonymized MRI head free-text radiology reports for abnormality and for small vessel disease presence. Of these reports, 80% (n = 1630) were used to fine-tune pretrained transformer models to classify scans. Five-fold cross-validation was used in model development. The models were tested on the remaining 20% of the reports (n = 408). SHapley Additive exPlanations (SHAP) were used to explain the …

Elevated Trna Halves In Olfactory Epithelial Cells Of Patients With Schizophrenia, Justin T. Gumas, Megumi Shigematsu, Karin E. Borgmann-Winter, C. G. Hahn, Yohei Kirino

Computational Medicine Center Faculty Papers

Schizophrenia patients' olfactory epithelial cells contain abundant immune-activating tRNA fragments, linking small RNA biology to inflammation and suggesting avenues for diagnostics.

Do Upside-Down Jellyfish Influence Marine Macrofauna Assemblages?, Juleika Y. Vega Pérez, Natalia B. Lopez-Figueroa, Sebastian Digeronimo, Michael J. Schram, Milton Muñoz Hincapie, Elizabeth Stoner, Pamela Hallock

Making Waves REU

• Estuaries are essential ecosystems for many organisms as they serve as spawning areas and nurseries
• Macrofauna are crucial members of estuarine ecosystems
• Many estuary macrofauna are considered of commercial importance
• Jellyfish blooms can alter nutrient cycling and modify habitat
• Little is known about how other macrofauna respond to Cassiopea blooms
• This study documents composition and diversity of macrofauna associated with Cassiopea blooms in Jobos Bay, Puerto Rico

A Programmable Genetic Platform For Engineering Noninvasive Biosensors, Asish N Chacko, Kaamini M Dhanabalan, Jinyang Wan, Roy Chien, Nolan T Anderson, Binzhi Xu, Katie Pham, Ritu Tiwari, Arnab Mukherjee

Faculty, Staff and Student Publications

Creating genetic sensors for noninvasive visualization of biological activities in optically opaque tissues holds immense potential for basic research and the development of genetic and cell-based therapies. Magnetic resonance imaging (MRI) stands out among deep tissue imaging methods for its ability to generate high-resolution images without ionizing radiation. However, the adoption of MRI as a mainstream biomolecular technology has been hindered by the lack of adaptable methods to link molecular events with genetically encodable contrast. Here, we introduce modular aquaporin-based protease-activatable probes for enhanced reporting (MAPPER), a platform for the systematic creation of genetic sensors for MRI. To develop MAPPER, …

Prevalence Of Depression Among Doctors In General Hospitals Of Basrah City Center During The Covid-19 Pandemic, Riham Sabri Saleh, Amaleed Kadhum, Raya Habeeb Abdulimam

Iraqi National Journal of Medicine

Background: Depression is the most common mental disorder in community settings and a major cause of disability worldwide. In 1999, it was the fourth most common cause of disability globally, and by 2020, it is projected to become the second most common cause. Doctors, as the primary workforce in hospitals, endure significant emotional and physical stress, which may have been exacerbated by the COVID-19 pandemic. Aim: This study aimed to estimate the prevalence of depression among doctors during the COVID-19 pandemic and its risk factors. Methods: This descriptive cross-sectional study was conducted from February 1 to June 1, 2021. The …

Clinicopathological Features Of Colorectal Cancer In Young Patients In Comparison With Older Patients, Bahaa Al-Neama, Wasam Al-Asadi

Iraqi National Journal of Medicine

Background:  Colorectal cancer (CRC) has traditionally been considered a disease of older adults; however, recent evidence shows an increasing incidence among younger patients. Understanding the differences in clinicopathological features between young and older individuals is essential for improving early diagnosis, treatment strategies, and outcomes. Aim: The primary objective of this study is to compare the demographic profiles and clinicopathological characteristics of younger patients (aged <40 years) with those of older patients (aged ≥40 years) diagnosed with colorectal cancer. Methods: Eighty-five consecutive patients admitted to our hospital were prospectively followed for their entire hospital stay or up to 7 days, whichever came first. Each patient's blood glucose measurement was recorded according to ward protocol. Indices included total blood glucose per ward, per patient-day, or patient stay, and percentage blood glucose levels per predefined cut points to assess the incidence of hypo-, eu-, and hyperglycemia. The trial registration number at Clinicaltrials.org is NCT04800861. Results: Total data consisted of 645 blood glucose tests from 85 patients and 284 patient-day results, with an average of 2.27 tests per patient-day and 7.59 measurements per patient stay. The percentage of blood glucose in the range (80–180 mg/dL) varied by model, with patient-day showing the highest results at 48.24%, while the percentage of patients with hypoglycemia (blood glucose <60 mg/dL) was highest per patient stay at 1.18%. Conclusions: Younger colorectal cancer patients in this study presented more frequently with rectal tumors, poor differentiation, and advanced disease stages. Despite similar symptom profiles, delayed diagnosis may contribute to worse pathological features. These findings support the need for greater awareness and consideration of earlier screening in younger populations.

Opioid Use After Screw Fixation Of Slipped Capital Femoral Epiphysis., Jonathan R. Warren, Stephanie Coupal, Colleen M. Moreland, Mckenna C. Noe, George E. Quaye, Lisa Berglund, Caleb W. Grote

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is a common pediatric hip disorder primarily managed with transphyseal screw fixation. Opioid pain medication is often used postoperatively, but there is little evidence to guide prescribing practices. The purpose of this study was to describe opioid utilization and prescribing practices for patients after screw fixation of SCFE.

METHODS: This was a prospective observational study of patients with SCFE who underwent transphyseal screw fixation. Patients and guardians were contacted on postoperative days 1, 3, and 5 for data collection. Postdischarge analgesic use, pain severity using a parental proxy, and pain control satisfaction were recorded. …

Aberrant Cd25 And Increased Cd123 Expression Are Common In Acute Myeloid Leukemia With Kmt2a Partial Tandem Duplication And Are Associated With Flt3 Internal Tandem Duplication, Qing Wei, Guilin Tang, Shaoying Li, Sa A Wang, Pei Lin, Wei Wang, Sanam Loghavi, Wei J Wang, L Jeffrey Medeiros, Jie Xu

Faculty, Staff and Student Publications

Background: KMT2A partial tandem duplication (PTD) occurs in approximately 5-10% of acute myeloid leukemia (AML) cases and is associated with poor prognosis. While its cytogenetic and molecular features are well described, the immunophenotypic characteristics of AML with KMT2A-PTD remain incompletely defined.

Methods: We identified 47 cases of AML with KMT2A-PTD by optical genome mapping. All cases underwent flow cytometric immunophenotypic analysis and next-generation sequencing using an 81-gene panel.

Results: The cohort included 32 men and 15 women with a median age of 67 years (range, 19-87). Thirty-eight cases were de novo AML, and nine were secondary to myelodysplastic …

Emt-Induced Stem Cell And Mesenchymal Programs Can Be Decoupled Via Cell Division And Esrp1-Dependent Mechanisms, Petra Den Hollander, Maria Castaneda, Suhas V Vasaikar, Joanna Joyce Maddela, Claire Gould, Breanna R Demestichas, Robiya Joseph, Shivangi Agarwal, Abhijeet P Deshmukh, Alvina Zia, Shruti Shah, Tieling Zhou, Geraldine Raja, Paul Allegakoen, Nick A Kuburich, Mika Pietila, Chunxiao Fu, Jeffrey Chang, Chad J Creighton, William F Symmans, Rama Soundararajan, Sendurai A Mani

Faculty, Staff and Student Publications

Epithelial-to-mesenchymal transition (EMT) is known to induce both stemness and mesenchymal properties, and our findings reveal that these two programs can be uncoupled. During EMT, epithelial cells transition from symmetric divisions producing differentiated daughter cells to self-renewing daughter cells. When we block cell division and induce EMT, cells gain mesenchymal properties but not stemness, suggesting the importance of cell division for gaining stemness. We identified ESRP1 as a key regulator of EMT-driven stemness, which get downregulated during EMT in a cell division-dependent manner. Overexpression of ESRP1 prevents the gain of stemness without affecting the mesenchymal program. Only the stemness and …

Role Of The Etv5/P38 Signaling Axis In Aggressive Thyroid Cancer Cells, Jerry H Houl, Rozita Bagheri-Yarmand, Muthusamy Kunnimalaiyaan, Paola Miranda Mendez, Joseph L Kidd, Ali Dadbin, Andrea Ruiz-Jurado, Parag A Parekh, Ying C Henderson, Nikhil S Chari, Aatish Thennavan, Reid T Powell, Clifford C Stephan, Xiao Zhao, Anastasios Maniakas, Roza Nurieva, Naifa L Busaidy, Maria E Cabanillas, Ramona Dadu, Mark Zafereo, Jennifer R Wang, Stephen Y Lai, Marie-Claude Hofmann

Faculty, Staff and Student Publications

Patients with poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) face a much poorer prognosis than those with differentiated thyroid cancers. Around 25% of PDTCs and 35% of ATCs carry the BRAFV600E mutation, which constitutively activates the MAPK pathway, a key driver of cell growth. Although combining BRAF and MEK inhibitors can shrink tumors, resistance often develops. The exact cause of this resistance remains unclear. We previously found that in PDTC and ATC cells, the BRAFV600E mutation is strongly linked to the expression of ETV5, a transcription factor downstream of the MAPK pathway. In the current study, we …

Advances In Targeting Her2 Across Cancer Subtypes: A Pan-Tumor Approach, Taiwo Adesoye, Ecaterina E Dumbrava, Kanwal P S Raghav, Aysegul A Sahin, Hui Chen, Sunyoung S Lee, Milind M Javle, Shubham Pant, Omar Alhalabi, Xiuning Le, Vicente Valero, Paula R Pohlmann, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Human epidermal growth factor receptor 2 (HER2) is an established therapeutic target in multiple solid tumors, particularly breast and gastric cancers. Significant advancements have been made in the development of HER2-targeted therapies, including monoclonal antibodies, tyrosine kinase inhibitors, antibody-drug conjugates (ADC), and novel bispecific antibodies. These agents have revolutionized the treatment landscape for HER2-positive metastatic cancers, resulting in improved progression-free and overall survival, and quality of life for patients. Beyond breast and gastric cancers, HER2 expression/amplification has been observed in other solid tumors, such as colorectal, lung, bladder, ovarian, and biliary tract cancers, offering new opportunities for personalized therapy in …

Host-Specific Fluorescence Dynamics In Legume-Rhizobium Symbiosis During Nodulation, Chandan K. Gautam, Gayathri Senanayake, Amanda B. Pease, Mohamed A. Salem, Ahmed H. Rabia, Birgit M. Prüß, Barney A. Geddes

APC Fund Awardees

The legume-rhizobium symbiosis is a cornerstone of sustainable agriculture due to its ability to facilitate biological nitrogen fixation. Still, real-time visualization and quantification of this interaction remain technically challenging, especially across different host backgrounds. In this study, we systematically evaluate the efficacyefficacyefficacyof the nitrogenase system nifH promoter (PnifH) in driving expression of distinct fluorescent reporters; superfolder yellow fluorescent protein (sfYFP), superfolder cyan fluorescent protein (sfCFP), and various red fluorescent proteins (RFPs) within root nodules of determinate (Lotus japonicus-Mesorhizobium japonicum) and indeterminate (Pisum sativum-Rhizobium leguminosarum) systems. We show that PnifH-driven sfYFP and sfCFP yield strong, uniform, and reproducible fluorescence in nodules …

Selective Deletion Of Slc2a1 From The Rpe Reveals That Rods But Not Cones Depend On Glucose Transport Across The Outer Blood-Retinal Barrier, Lauren L. Daniele, John Y.S. Han, Minzhong Yu, Ravi A. Sangani, Craig D. Beight, Cyrus Rostami, Philip D. Kiser, Neal S. Peachy, Nancy J. Philp

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

GLUT1 facilitates a continuous flow of glucose across the inner and outer blood-retinal barriers (BRBs) to support vision. To understand the extent to which photoreceptors rely on glucose transport across the outer BRB, we generated a tamoxifen-inducible conditional knockout of Slc2a1 in the retinal pigment epithelium (RPE) (RPE-iΔGlut1). In the RPE-iΔGlut1 mice, rod photoreceptors exhibited impaired outer segment renewal and decreased the expression of proteins involved in phototransduction and ciliary transport. Proteins regulating the retinal stress response increased. Cone photoreceptors were functional and viable 15 months post-tamoxifen treatment in the RPE-iΔGlut1 mice, while 70% of the rods died. …

Optimal Murine Cd4+ T Cell Priming By Mrna-Lipid Nanoparticle Vaccines Requires Endogenous Antigen Processing, Julia E. Rood, Suh Kyung Yoon, Mary K. Heard, Stephen D. Carro, Emma J. Hedgepeth, Mary E. O'Mara, Michael J. Hogan, Nhu Le, Hiromi Muramatsu, Kieu Lam, Petra Schreiner, Coral Kasden, Hansell H. Stedman, Ryan A. Langlois, James Heyes, Norbert Pardi, Laurence C. Eisenlohr

College of Life Sciences Faculty Papers

Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines elicit robust CD4+ T cell responses, yet the mechanisms underlying this T cell priming remain unknown. Antigens presented to CD4+ T cells on major histocompatibility complex class II (MHC II) are traditionally acquired by antigen presenting cells (APCs) from extracellular sources. Here we show that vaccine specific CD4+ T cell responses instead rely on antigen directly expressed within APCs, without extracellular transit. Murine APCs treated with mRNA-LNP vaccines activate T cells more efficiently when presenting antigen produced internally, rather than acquired externally. Immunization with mRNA-LNP vaccines engineered to inhibit antigen expression in APCs results …

Single-Cell Rna Sequencing Suggests Different Progenitor Lineages Between Idh Mutant And Idhwt Glioma, Iyad Alnahhas, Allison Kayne, Mehak Khan, Wenyin Shi

Department of Neurology Faculty Papers

Introduction Single-cell RNA sequencing has elucidated the heterogeneity in cancer. Single-cell glioblastoma (GBM) analyses have also proposed the resemblance of GBM cells to radial glia and outer radial glia (oRG) supporting the hypothesis that remnants of developmental tissue get reactivated in cancer. A recent study isolated neural progenitor cells (NPCs) from developing fetal human brain (gestational week 17-19) and classified NPCs based on their expression of THY1 (CD90), CD24 and EGFR. Ventricular radial glia are THY1⁻CD24⁻EGFR⁺ whereas oRG are THY1⁻CD24⁻EGFR⁻. Early neuron precursors are CD24⁺THY1⁻EGFR …

Cold Atmospheric Plasma For Prostate Cancer Therapy—Potential For Clinical Translation, Shengxin Zhang, Janith Wanigasekara, Daniela Boehm, James F. Curtin, Paula Bourke, Tao Zhang, Gemma K. Kinsella

Research Outputs: 2025-Present

Cold atmospheric plasma (CAP) has potential as a new cancer treatment tool due to its room temperature biocompatibility and possible cancer cell selectivity with low side effects. This review examines the current research stage of CAP therapy for Prostate Cancer (PCa) treatment with a focus on CAP device standardization and CAP therapy clinical translation. The current CAP preclinical data is explored through the lens of PCa cellular response, PCa cells selectivity, CAP treatment type and CAP combination therapies. Finally, building on the current preclinical data, this review proposes the potential clinical application methods of CAP at different PCa stages to …

The Ethical Limits Of Physician Autonomy In Reproductive Medicine, Isabel Martens

Honors Theses

In vitro fertilization is a relatively new medical practice that helps people who face infertility be able to reproduce. Reproductive medicine providers face ethical dilemmas often in their field, only some of which have standards of care. There are questions in the medical landscape pertaining to physician autonomy versus patient autonomy, which heavily apply to reproductive medicine providers. Patient autonomy is highly valued in medical ethics; however, physician autonomy should also be considered. When a physician decides who can and cannot reproduce, ethical considerations must be followed to maintain the practice of reproductive autonomy. Limited policies exist that manage reproductive …

Combining Dna Methylation Features And Clinical Characteristics Predicts Ketamine Treatment Response For Ptsd, Amir Valizadeh, John D Roache, Xinyu Zhang, Ying Hu, Ralitza Gueorguieva, Lynnette A Averill, Mohini Ranganathan, Zuoheng Wang, Douglas E Williamson, Paulo R Shiroma, Matthew J Girgenti, Ismene L Petrakis, Argelio L López-Roca, Stacey Young-Mccaughan, Terence M Keane, Alan L Peterson, Chadi G Abdallah, John H Krystal, Ke Xu

Staff and Researcher Publications

Post-traumatic stress disorder (PTSD) exhibits extensive clinical and biological variability, making treatment challenging. The Consortium to Alleviate PTSD (CAP)-ketamine trial, the largest randomized study of ketamine for PTSD, found no overall benefit of ketamine over placebo, underscoring the necessity to identify responsive subgroups. Using pre-treatment blood DNA methylation profiles and clinical measures from the CAP-ketamine trial, we applied machine learning to predict treatment response. A model based on 1,208 methylation sites achieved higher predictive accuracy than models using clinical variables alone, and combining both data types further improved performance. The methylation-derived score distinguished responders with 92.9% accuracy. The predictive CpGs …

Rare Heterozygous De Novo Variants In Rapgef2 Are Associated With A Neurodevelopmental Disorder, Ali H Bereshneh, Kirkland A Wilson, Xueyang Pan, Shabab B Hannan, Megan A Cooper, Jullianne Diaz, Eyby Leon, Tiana M Moses, Mahshid S Azamian, Daryl A Scott, Ping Yee Billie Au, Juan Pablo Appendino, Ingrid E Scheffer, Antony Kaspi, Melanie Bahlo, Michael S Hildebrand, Angela T Morgan, Ekanem Ekure, Joshua M Shulman, Friedhelm Hildebrandt, Jennifer E Posey, Paul Kruszka, Eric Vilain, Shinya Yamamoto, Oguz Kanca, Seth Berger, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Purpose: RAPGEF2 encodes a guanine nucleotide exchange factor (GEF) that activates small GTPases and has not been linked to a Mendelian disorder. RAPGEF2 is highly intolerant to loss-of-function variants. We report 5 de novo heterozygous variants in RAPGEF2 in unrelated individuals with developmental delay, attention deficit hyperactivity disorder, epilepsy, dysmorphic features, or other manifestations. We used a Drosophila model to assess the functional impact of the identified human variants.

Methods: We generated a Kozak-GAL4 null allele of the Drosophila ortholog of RAPGEF2, PDZ-GEF, and used the allele to determine the gene expression pattern as well as the loss-of-function phenotypes. We …