Digital Commons Network^™

Noninferiority Of Hypofractionated Vs Conventional Postprostatectomy Radiotherapy For Genitourinary And Gastrointestinal Symptoms: The Nrg-Gu003 Phase 3 Randomized Clinical Trial, Mark K Buyyounouski, Stephanie L Pugh, Ronald C Chen, Mark J Mann, Rajat J Kudchadker, Andre A Konski, Omar Y Mian, Jeff M Michalski, Eric Vigneault, Richard K Valicenti, Maroie Barkati, Colleen A F Lawton, Louis Potters, Drew C Monitto, Jeffrey A Kittel, Thomas M Schroeder, Raquibul Hannan, Casey E Duncan, Joseph P Rodgers, Felix Feng, Howard M Sandler

Faculty, Staff and Student Publications

Importance: No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy.

Objective: To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years.

Design, setting, and participants: In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (< 0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed.

Intervention: Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT).

Main outcomes and measures: The coprimary end points were the 2-year …

Antihypertensive Medications And Risk Of Melanoma And Keratinocyte Carcinomas: A Systematic Review And Meta-Analysis, Olivia G Cohen, Matthew Taylor, Cassandra Mohr, Kevin T Nead, Candice L Hinkston, Sharon H Giordano, Sinead M Langan, David J Margolis, Mackenzie R Wehner

Faculty, Staff and Student Publications

Some antihypertensive medications are photosensitizing. The implications for skin cancer risk remain unclear because results from prior studies are inconsistent and as new evidence is published. We performed a systematic review and meta-analysis to evaluate the association between antihypertensives and common skin cancers (cutaneous squamous cell carcinoma, basal cell carcinoma, and melanoma) and to evaluate dose-response relationships. Forty-four articles met inclusion criteria, and 42 could be meta analyzed. Increased risks were seen for basal cell carcinoma with calcium channel blockers (relative risk [RR] = 1.17, 95% confidence interval [CI] = 1.11-1.22), diuretics (RR = 1.06, 95% CI = 1.03-1.10), and …

A Radiotherapy Community Data-Driven Approach To Determine Which Complexity Metrics Best Predict The Impact Of Atypical Tps Beam Modeling On Clinical Dose Calculation Accuracy, Fre'etta Mae Dayo Brooks, Mallory Carson Glenn, Victor Hernandez, Jordi Saez, Hunter Mehrens, Julianne Marie Pollard-Larkin, Rebecca Maureen Howell, Christine Burns Peterson, Christopher Lee Nelson, Catharine Helen Clark, Stephen Frasier Kry

Faculty, Staff and Student Publications

PURPOSE: To quantify the impact of treatment planning system beam model parameters, based on the actual spread in radiotherapy community data, on clinical treatment plans and determine which complexity metrics best describe the impact beam modeling errors have on dose accuracy.

METHODS: Ten beam modeling parameters for a Varian accelerator were modified in RayStation to match radiotherapy community data at the 2.5, 25, 50, 75, and 97.5 percentile levels. These modifications were evaluated on 25 patient cases, including prostate, non-small cell lung, H&N, brain, and mesothelioma, generating 1,000 plan perturbations. Differences in the mean planned dose to clinical target volumes …

Social Support In An Internet Weight Loss Community, Richard Freund, Marta Favara, Catherine Porter, Jere Behrman

Faculty, Staff and Student Publications

Many low- and middle-income countries have introduced public works programs (PWPs) to fight poverty. This paper provides the first evidence that children from families who benefit from PWPs show increased foundational cognitive skills. The results, based on unique tablet-based data collected as part of a long-standing longitudinal survey, show positive associations between participation in the Productive Safety Net Programme (PSNP) in Ethiopia during childhood with long-term memory and implicit learning, and suggestive evidence for working memory. These associations appear to be strongest for children whose households were still PSNP participants in the year of data collection. Evidence suggests that the …

Diagnosing Autism In Adults: Clinically Focused Recommendations, Antonio F Pagán, Daniel D Flint, Katherine A Loveland

Faculty, Staff and Student Publications

Autism is sometimes missed in childhood and can be associated with co-occurring conditions (e.g., attention-deficit/hyperactivity disorder or anxiety) and lower quality of life in adulthood. The present paper seeks to provide concise and up-to-date information for practicing clinicians who are tasked with evaluating potentially autistic adults who were not diagnosed in childhood. For assessments of autism, practicing clinicians should consider many factors in adults, including "masking" symptoms, sex or gender differences, and family reports of developmental history when available. Treatment providers should tailor their interventions to include psychoeducation about autism symptoms for newly diagnosed autistic adults. Clinicians should utilize a …

Light Scattering By Vitreous Of Humans With Vision Degrading Myodesopsia From Floaters, Alba M Paniagua-Diaz, Justin H Nguyen, Pablo Artal, Wei Gui, J Sebag

Faculty, Staff and Student Publications

PURPOSE: Vision-degrading myodesopsia (VDM) from vitreous floaters significantly degrades vision and impacts visual quality of life (VQOL), but the relationship to light scattering is poorly understood. This study compared in vitro measures of light scatter and transmission in surgically excised human vitreous to preoperative indexes of vitreous structure, visual function, and VQOL.

METHODS: Pure vitreous collected during vitrectomy from 8 patients with VDM had wide-angle straylight measurements and dark-field imaging, performed within 36 hours of vitrectomy. Preoperative VQOL assessment with VFQ-25, contrast sensitivity (CS) measurements with Freiburg acuity contrast testing, and quantitative ultrasonography were compared to light scattering and transmission …

Alteration In Resting-State Brain Activity In Stroke Survivors After Repetitive Finger Stimulation, Dorothy He, William A Sikora, Shirley A James, Jordan N Williamson, Louis V Lepak, Carolyn F Cheema, Evgeny Sidorov, Sheng Li, Yuan Yang

Faculty, Staff and Student Publications

Objective: This quasi-experimental study examined the effect of repetitive finger stimulation on brain activation in eight stroke and seven control subjects, measured by quantitative electroencephalogram.

Methods: We applied 5 mins of 2-Hz repetitive bilateral index finger transcutaneous electrical nerve stimulation and compared differences pre- and post-transcutaneous electrical nerve stimulation using quantitative electroencephalogram metrics delta/alpha ratio and delta-theta/alpha-beta ratio.

Results: Between-group differences before and after stimulation were significantly different in the delta/alpha ratio ( z = -2.88, P = 0.0040) and the delta-theta/alpha-beta ratio variables ( z = -3.90 with P < 0.0001). Significant decrease in the delta/alpha ratio and delta-theta/alpha-beta ratio variables after the transcutaneous electrical nerve stimulation was detected only in the stroke group (delta/alpha ratio diff = 3.87, P = 0.0211) (delta-theta/alpha-beta ratio diff = 1.19, P = 0.0074).

Conclusions: The decrease in quantitative electroencephalogram metrics in the stroke …

Practice Facilitation And Peer Coaching For Uncontrolled Hypertension Among Black Individuals: A Randomized Clinical Trial, Monika M Safford, Doyle M Cummings, Jacqueline R Halladay, James M Shikany, Joshua Richman, Suzanne Oparil, James Hollenberg, Alyssa Adams, Muna Anabtawi, Lynn Andreae, Elizabeth Baquero, Joanna Bryan, Debra Sanders-Clark, Ethel Johnson, Erica Richman, Orysya Soroka, Jimmy Tillman, Andrea L Cherrington

Faculty, Staff and Student Publications

IMPORTANCE: Rural Black participants need effective intervention to achieve better blood pressure (BP) control.

OBJECTIVE: Among Black rural adults with persistently uncontrolled hypertension attending primary care clinics, to determine whether peer coaching (PC), practice facilitation (PF), or both (PCPF) are superior to enhanced usual care (EUC) in improving BP control.

DESIGN, SETTING, AND PARTICIPANTS: A cluster randomized clinical trial was conducted in 69 rural primary care practices across Alabama and North Carolina between September 23, 2016, and September 26, 2019. The participating practices were randomized to 4 groups: PC plus EUC, PF plus EUC, PCPF plus EUC, and EUC alone. …

Simultaneous Hemorrhage And Venous Thrombosis In A Patient With Systemic Lupus Erythematosus, Binoy Yohannan, Natalie A Montanez, Miguel A Escobar

Faculty, Staff and Student Publications

No abstract provided.

Cross-Vendor Multiparametric Mapping Of The Human Brain Using 3d-Qalas: A Multicenter And Multivendor Study, Shohei Fujita, Borjan Gagoski, Ken-Pin Hwang, Akifumi Hagiwara, Marcel Warntjes, Issei Fukunaga, Wataru Uchida, Yuya Saito, Towa Sekine, Rina Tachibana, Tomoya Muroi, Toshiya Akatsu, Akihiro Kasahara, Ryo Sato, Tsuyoshi Ueyama, Christina Andica, Koji Kamagata, Shiori Amemiya, Hidemasa Takao, Yasunobu Hoshino, Yuji Tomizawa, Kazumasa Yokoyama, Berkin Bilgic, Nobutaka Hattori, Osamu Abe, Shigeki Aoki

Faculty, Staff and Student Publications

Purpose: To evaluate a vendor-agnostic multiparametric mapping scheme based on 3D quantification using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (3D-QALAS) for whole-brain T1, T2, and proton density (PD) mapping.

Methods: This prospective, multi-institutional study was conducted between September 2021 and February 2022 using five different 3T systems from four prominent MRI vendors. The accuracy of this technique was evaluated using a standardized MRI system phantom. Intra-scanner repeatability and inter-vendor reproducibility of T1, T2, and PD values were evaluated in 10 healthy volunteers (6 men; mean age ± SD, 28.0 ± 5.6 y) who underwent scan-rescan sessions …

Deep Learning-Based Automatic Classification Of Ischemic Stroke Subtype Using Diffusion-Weighted Images, Wi-Sun Ryu, Dawid Schellingerhout, Hoyoun Lee, Keon-Joo Lee, Chi Kyung Kim, Beom Joon Kim, Jong-Won Chung, Jae-Sung Lim, Joon-Tae Kim, Dae-Hyun Kim, Jae-Kwan Cha, Leonard Sunwoo, Dongmin Kim, Sang-Il Suh, Oh Young Bang, Hee-Joon Bae, Dong-Eog Kim

Faculty, Staff and Student Publications

Background and purpose: Accurate classification of ischemic stroke subtype is important for effective secondary prevention of stroke. We used diffusion-weighted image (DWI) and atrial fibrillation (AF) data to train a deep learning algorithm to classify stroke subtype.

Methods: Model development was done in 2,988 patients with ischemic stroke from three centers by using U-net for infarct segmentation and EfficientNetV2 for subtype classification. Experienced neurologists (n=5) determined subtypes for external test datasets, while establishing a consensus for clinical trial datasets. Automatically segmented infarcts were fed into the model (DWI-only algorithm). Subsequently, another model was trained, with AF included as a categorical …

The Constitutively Active Form Of A Key Cholesterol Synthesis Enzyme Is Lipid Droplet-Localized And Upregulated In Endometrial Cancer Tissues, Hudson W Coates, Tina B Nguyen, Ximing Du, Ellen M Olzomer, Rhonda Farrell, Frances L Byrne, Hongyuan Yang, Andrew J Brown

Faculty, Staff and Student Publications

Cholesterol is essential for both normal cell viability and cancer cell proliferation. Aberrant activity of squalene monooxygenase (SM, also known as squalene epoxidase), the rate-limiting enzyme of the committed cholesterol synthesis pathway, is accordingly implicated in a growing list of cancers. We previously reported that hypoxia triggers the truncation of SM to a constitutively active form, thus preserving sterol synthesis during oxygen shortfalls. Here, we show SM truncation is upregulated and correlates with the magnitude of hypoxia in endometrial cancer tissues, supporting the in vivo relevance of our earlier work. To further investigate the pathophysiological consequences of SM truncation, we …

The Intrinsic Substrate Specificity Of The Human Tyrosine Kinome, Tomer M Yaron-Barir, Brian A Joughin, Emily M Huntsman, Alexander Kerelsky, Daniel M Cizin, Benjamin M Cohen, Amit Regev, Junho Song, Neil Vasan, Ting-Yu Lin, Jose M Orozco, Christina Schoenherr, Cari Sagum, Mark T Bedford, R Max Wynn, Shih-Chia Tso, David T Chuang, Lei Li, Shawn S-C Li, Pau Creixell, Konstantin Krismer, Mina Takegami, Harin Lee, Bin Zhang, Jingyi Lu, Ian Cossentino, Sean D Landry, Mohamed Uduman, John Blenis, Olivier Elemento, Margaret C Frame, Peter V Hornbeck, Lewis C Cantley, Benjamin E Turk, Michael B Yaffe, Jared L Johnson

Faculty, Staff and Student Publications

Phosphorylation of proteins on tyrosine (Tyr) residues evolved in metazoan organisms as a mechanism of coordinating tissue growth1. Multicellular eukaryotes typically have more than 50 distinct protein Tyr kinases that catalyse the phosphorylation of thousands of Tyr residues throughout the proteome1-3. How a given Tyr kinase can phosphorylate a specific subset of proteins at unique Tyr sites is only partially understood4-7. Here we used combinatorial peptide arrays to profile the substrate sequence specificity of all human Tyr kinases. Globally, the Tyr kinases demonstrate considerable diversity in optimal patterns of residues surrounding the site of phosphorylation, revealing the functional organization of …

Enhanced Ctla-4 Blockade Anti-Tumor Immunity With Apg-157 Combination In A Murine Head And Neck Cancer, Daniel Sanghoon Shin, Saroj Basak, Mysore S Veena, Begoña Comin-Anduix, Arjun Bhattacharya, Tien S Dong, Albert Ko, Philip Han, Jonathan Jacobs, Neda A Moatamed, Luis Avila, Matteo Pellegrini, Marilene Wang, Eri S Srivatsan

Faculty, Staff and Student Publications

BACKGROUND: A phase I clinical study for patients with locally advanced H&N cancer with a new class of botanical drug APG-157 provided hints of potential synergy with immunotherapy. We sought to evaluate the efficacy of the combination of APG-157 and immune checkpoint inhibitors.

METHODS: CCL23, UM-SCC1 (human), and SCCVII (HPV-), MEER (HPV+) (murine) H&N cancer cell lines were utilized for in vitro and in vivo studies. We measured tumor growth by treating the mice with APG-157, anti-PD-1, and anti-CTLA-4 antibody combinations (8 groups). The tumor microenvironments were assessed by multi-color flow cytometry, immunohistochemistry, and RNA-seq analysis. Fecal microbiome was analyzed …

Foundation Models, Generative Ai, And Large Language Models: Essentials For Nursing, Angela Ross, Kathleen Mcgrow, Degui Zhi, Laila Rasmy

Faculty, Staff and Student Publications

We are in a booming era of artificial intelligence, particularly with the increased availability of technologies that can help generate content, such as ChatGPT. Healthcare institutions are discussing or have started utilizing these innovative technologies within their workflow. Major electronic health record vendors have begun to leverage large language models to process and analyze vast amounts of clinical natural language text, performing a wide range of tasks in healthcare settings to help alleviate clinicians' burden. Although such technologies can be helpful in applications such as patient education, drafting responses to patient questions and emails, medical record summarization, and medical research …

Montelukast As A Repurposable Additive Drug For Standard-Efficacy Multiple Sclerosis Treatment: Emulating Clinical Trials With Retrospective Administrative Health Claims Data, Astrid M Manuel, Assaf Gottlieb, Leorah Freeman, Zhongming Zhao

Faculty, Staff and Student Publications

BACKGROUND: Effective and safe treatment options for multiple sclerosis (MS) are still needed. Montelukast, a leukotriene receptor antagonist (LTRA) currently indicated for asthma or allergic rhinitis, may provide an additional therapeutic approach.

OBJECTIVE: The study aimed to evaluate the effects of montelukast on the relapses of people with MS (pwMS).

METHODS: In this retrospective case-control study, two independent longitudinal claims datasets were used to emulate randomized clinical trials (RCTs). We identified pwMS aged 18-65 years, on MS disease-modifying therapies concomitantly, in de-identified claims from Optum's Clinformatics

RESULTS: pwMS treated with montelukast demonstrated a statistically significant 23.6% reduction in relapses compared …

Mapping Genotypes To Chromatin Accessibility Profiles In Single Cells, Franco Izzo, Robert M Myers, Saravanan Ganesan, Levan Mekerishvili, Sanjay Kottapalli, Tamara Prieto, Elliot O Eton, Theo Botella, Andrew J Dunbar, Robert L Bowman, Jesus Sotelo, Catherine Potenski, Eleni P Mimitou, Maximilian Stahl, Sebastian El Ghaity-Beckley, Joann Arandela, Ramya Raviram, Daniel C Choi, Ronald Hoffman, Ronan Chaligné, Omar Abdel-Wahab, Peter Smibert, Irene M Ghobrial, Joseph M Scandura, Bridget Marcellino, Ross L Levine, Dan A Landau

Faculty, Staff and Student Publications

In somatic tissue differentiation, chromatin accessibility changes govern priming and precursor commitment towards cellular fates1-3. Therefore, somatic mutations are likely to alter chromatin accessibility patterns, as they disrupt differentiation topologies leading to abnormal clonal outgrowth. However, defining the impact of somatic mutations on the epigenome in human samples is challenging due to admixed mutated and wild-type cells. Here, to chart how somatic mutations disrupt epigenetic landscapes in human clonal outgrowths, we developed genotyping of targeted loci with single-cell chromatin accessibility (GoT-ChA). This high-throughput platform links genotypes to chromatin accessibility at single-cell resolution across thousands of cells within a single assay. …

Automated, High-Throughput Platform To Generate A High-Reliability, Comprehensive Rectal Cancer Database, Neal Bhutiani, Mahmoud M G Yousef, Abdelrahman Yousef, Mohammad Zeineddine, Mark Knafl, Olivia Ratliff, Uditha P Fernando, Anastasia Turin, Fadl A Zeineddine, Jeff Jin, Kristin Alfaro-Munoz, Drew Goldstein, George J Chang, Scott Kopetz, John Paul Shen, Abhineet Uppal

Faculty, Staff and Student Publications

Purpose: Dynamic operations platforms allow for cross-platform data extraction, integration, and analysis, although application of these platforms to large-scale oncology enterprises has not been described. This study presents a pipeline for automated, high-fidelity extraction, integration, and validation of cross-platform oncology data in patients undergoing treatment for rectal cancer at a single, high-volume institution.

Methods: A dynamic operations platform was used to identify patients with rectal cancer treated at MD Anderson Cancer Center between 2016 and 2022 who had magnetic resonance imaging (MRI) imaging and preoperative treatment details available in the electronic health record (EHR). Demographic, clinicopathologic, tumor mutation, radiographic, and …

Genomic Landscape Of Lynch Syndrome Colorectal Neoplasia Identifies Shared Mutated Neoantigens For Immunoprevention, Ana M Bolivar, Fahriye Duzagac, Nan Deng, Laura Reyes-Uribe, Kyle Chang, Wenhui Wu, Charles M Bowen, Melissa W Taggart, Selvi Thirumurthi, Patrick M Lynch, Y Nancy You, Jesus Rodriguez-Pascual, Steven M Lipkin, Scott Kopetz, Paul Scheet, Gregory A Lizee, Alexandre Reuben, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

Background & aims: Lynch syndrome (LS) carriers develop mismatch repair-deficient neoplasia with high neoantigen (neoAg) rates. No detailed information on targetable neoAgs from LS precancers exists, which is crucial for vaccine development and immune-interception strategies. We report a focused somatic mutation and frameshift-neoAg landscape of microsatellite loci from colorectal polyps without malignant potential (PWOMP), precancers, and early-stage cancers in LS carriers.

Methods: We generated paired whole-exome and transcriptomic sequencing data from 8 colorectal PWOMP, 41 precancers, 8 advanced precancers, and 12 early-stage cancers of 43 LS carriers. A computational pipeline was developed to predict, rank, and prioritize the top 100 …

Igwas: Image-Based Genome-Wide Association Of Self-Supervised Deep Phenotyping Of Retina Fundus Images, Ziqian Xie, Tao Zhang, Sangbae Kim, Jiaxiong Lu, Wanheng Zhang, Cheng-Hui Lin, Man-Ru Wu, Alexander Davis, Roomasa Channa, Luca Giancardo, Han Chen, Sui Wang, Rui Chen, Degui Zhi

Faculty, Staff and Student Publications

Existing imaging genetics studies have been mostly limited in scope by using imaging-derived phenotypes defined by human experts. Here, leveraging new breakthroughs in self-supervised deep representation learning, we propose a new approach, image-based genome-wide association study (iGWAS), for identifying genetic factors associated with phenotypes discovered from medical images using contrastive learning. Using retinal fundus photos, our model extracts a 128-dimensional vector representing features of the retina as phenotypes. After training the model on 40,000 images from the EyePACS dataset, we generated phenotypes from 130,329 images of 65,629 British White participants in the UK Biobank. We conducted GWAS on these phenotypes …

Circulating Immune Signatures In Chronic Pancreatitis With And Without Preceding Acute Pancreatitis: A Pilot Study, Rasmus Hagn-Meincke, Dhiraj Yadav, Dana K Andersen, Santhi Swaroop Vege, Evan L Fogel, Jose Serrano, Melena D Bellin, Mark D Topazian, Darwin L Conwell, Liang Li, Stephen K Van Den Eeden, Asbjørn M Drewes, Stephen J Pandol, Chris E Forsmark, William E Fisher, Phil A Hart, Søren S Olesen, Walter G Park, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Objective: To investigate profiles of circulating immune signatures in healthy controls and chronic pancreatitis patients (CP) with and without a preceding history of acute pancreatitis (AP).

Methods: We performed a phase 1, cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies (PROCEED) study. All samples were collected during a clinically quiescent phase. CP subjects were categorized into two subgroups based on preceding episode(s) of AP. Healthy controls were included for comparison. Blinded samples were analyzed using an 80-plex Luminex assay of cytokines, chemokines, and adhesion molecules. Group and pairwise comparisons …

Single-Nucleotide Variant Calling In Single-Cell Sequencing Data With Monopogen, Jinzhuang Dou, Yukun Tan, Kian Hong Kock, Jun Wang, Xuesen Cheng, Le Min Tan, Kyung Yeon Han, Chung-Chau Hon, Woong-Yang Park, Jay W Shin, Haijing Jin, Yujia Wang, Han Chen, Li Ding, Shyam Prabhakar, Nicholas Navin, Rui Chen, Ken Chen

Faculty, Staff and Student Publications

Single-cell omics technologies enable molecular characterization of diverse cell types and states, but how the resulting transcriptional and epigenetic profiles depend on the cell's genetic background remains understudied. We describe Monopogen, a computational tool to detect single-nucleotide variants (SNVs) from single-cell sequencing data. Monopogen leverages linkage disequilibrium from external reference panels to identify germline SNVs and detects putative somatic SNVs using allele cosegregating patterns at the cell population level. It can identify 100 K to 3 M germline SNVs achieving a genotyping accuracy of 95%, together with hundreds of putative somatic SNVs. Monopogen-derived genotypes enable global and local ancestry inference …

Alterations In Brain Morphometric Networks And Their Relationship With Memory Dysfunction In Patients With Type 2 Diabetes Mellitus, Rye Young Kim, Yoonji Joo, Eunji Ha, Haejin Hong, Chaewon Suh, Youngeun Shim, Hyeonji Lee, Yejin Kim, Jae-Hyoung Cho, Sujung Yoon, In Kyoon Lyoo

Faculty, Staff and Student Publications

Cognitive dysfunction, a significant complication of type 2 diabetes mellitus (T2DM), can potentially manifest even from the early stages of the disease. Despite evidence of global brain atrophy and related cognitive dysfunction in early-stage T2DM patients, specific regions vulnerable to these changes have not yet been identified. The study enrolled patients with T2DM of less than five years’ duration and without chronic complications (T2DM group, n=100) and demographically similar healthy controls (control group, n=50). High-resolution T1-weighted magnetic resonance imaging data were subjected to independent component analysis to identify structurally significant components indicative of morphometric networks. Within these networks, the groups’ …

A Matter Of Time: How Musical Training Affects Time Perception, Jahanvi Mittal, Khushi Kaur Juneja, Saumya Saumya, Anuj Shukla

Faculty, Staff and Student Publications

Musical training has been linked to changes in early attentional and perceptual processing. Thus, such an altered attentional and perceptual processing has enabled musicians to judge the duration differently than non-musicians. Although these claims seem intriguing, there are many questions that are not addressed yet, for example, how would the performance of musically-trained differ from that of untrained on visual and auditory temporal judgments? Is there any advantage to musically-trained person in temporal processing? To understand these questions, we thus conducted a series of Auditory and Visual Temporal Bisection Tasks on 32 musically-trained and 32 musically-untrained participants. We hypothesized that …

Nestedbd: Bayesian Inference Of Phylogenetic Trees From Single-Cell Copy Number Profiles Under A Birth-Death Model, Yushu Liu, Mohammadamin Edrisi, Zhi Yan, Huw A Ogilvie, Luay Nakhleh

Faculty, Staff and Student Publications

Copy number aberrations (CNAs) are ubiquitous in many types of cancer. Inferring CNAs from cancer genomic data could help shed light on the initiation, progression, and potential treatment of cancer. While such data have traditionally been available via “bulk sequencing,” the more recently introduced techniques for single-cell DNA sequencing (scDNAseq) provide the type of data that makes CNA inference possible at the single-cell resolution. We introduce a new birth-death evolutionary model of CNAs and a Bayesian method, NestedBD, for the inference of evolutionary trees (topologies and branch lengths with relative mutation rates) from single-cell data. We evaluated NestedBD’s performance using …

Comprehensive Analysis Of Bulk And Single-Cell Transcriptomic Data Reveals A Novel Signature Associated With Endoplasmic Reticulum Stress, Lipid Metabolism, And Liver Metastasis In Pancreatic Cancer, Xiaohong Liu, Bo Ren, Yuan Fang, Jie Ren, Xing Wang, Minzhi Gu, Feihan Zhou, Ruiling Xiao, Xiyuan Luo, Lei You, Yupei Zhao

Faculty, Staff and Student Publications

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with high probability of recurrence and distant metastasis. Liver metastasis is the predominant metastatic mode developed in most pancreatic cancer cases, which seriously affects the overall survival rate of patients. Abnormally activated endoplasmic reticulum stress and lipid metabolism reprogramming are closely related to tumor growth and metastasis. This study aims to construct a prognostic model based on endoplasmic reticulum stress and lipid metabolism for pancreatic cancer, and further explore its correlation with tumor immunity and the possibility of immunotherapy.

METHODS: Transcriptomic and clinical data are acquired from TCGA, ICGC, and GEO …

Examining The Effect Of Genes On Depression As Mediated By Smoking And Modified By Sex, Kirsten Voorhies, Julian Hecker, Sanghun Lee, Georg Hahn, Dmitry Prokopenko, Merry-Lynn Mcdonald, Alexander C Wu, Ann Wu, John E Hokanson, Michael H Cho, Christoph Lange, Karin F Hoth, Sharon M Lutz

Faculty, Staff and Student Publications

Depression is heritable, differs by sex, and has environmental risk factors such as cigarette smoking. However, the effect of single nucleotide polymorphisms (SNPs) on depression through cigarette smoking and the role of sex is unclear. In order to examine the association of SNPs with depression and smoking in the UK Biobank with replication in the COPDGene study, we used counterfactual-based mediation analysis to test the indirect or mediated effect of SNPs on broad depression through the log of pack-years of cigarette smoking, adjusting for age, sex, current smoking status, and genetic ancestry (via principal components). In secondary analyses, we adjusted …

The Impact Of Family Functioning Factors On Smartphone Addiction And Phubbing Among Muslim Adolescents In Thailand, Yejin Kim, Wanchai Dhammasaccakarn, Kasetchai Laeheem, Idsaratt Rinthaisong

Faculty, Staff and Student Publications

BACKGROUND: While there is research on protective factors against smartphone addiction (SA) and phubbing, which impact adolescents' physical, psychological, interpersonal, and academic well-being, focused studies on these issues among Thai Muslim students in Southern Thailand remain scarce.

OBJECTIVES: To bridge this gap, this research aimed to explore the influence of five family functioning factors-discipline, communication and problem-solving (CPS), relationship, emotional status, and family support-guided by family systems theory and the McMaster Model, on SA and phubbing.

METHODS: Data from 825 Thai Muslim adolescent secondary school students (Female N = 459 (55.7%), M

RESULTS: Significant connections were identified between family functioning …

The Swi/Snf Atp-Dependent Chromatin Remodeling Complex In Cell Lineage Priming And Early Development, Dhurjhoti Saha, Srinivas Animireddy, Blaine Bartholomew

Faculty, Staff and Student Publications

ATP dependent chromatin remodelers have pivotal roles in transcription, DNA replication and repair, and maintaining genome integrity. SWI/SNF remodelers were first discovered in yeast genetic screens for factors involved in mating type switching or for using alternative energy sources therefore termed SWI/SNF complex (short for SWItch/Sucrose NonFermentable). The SWI/SNF complexes utilize energy from ATP hydrolysis to disrupt histone-DNA interactions and shift, eject, or reposition nucleosomes making the underlying DNA more accessible to specific transcription factors and other regulatory proteins. In development, SWI/SNF orchestrates the precise activation and repression of genes at different stages, safe guards the formation of specific cell …

An Approach To Identify Gene-Environment Interactions And Reveal New Biological Insight In Complex Traits, Xiaofeng Zhu, Yihe Yang, Noah Lorincz-Comi, Gen Li, Amy R Bentley, Paul S De Vries, Michael Brown, Alanna C Morrison, Charles N Rotimi, W James Gauderman, Dabeeru C Rao, Hugues Aschard

Faculty, Staff and Student Publications

There is a long-standing debate about the magnitude of the contribution of gene-environment interactions to phenotypic variations of complex traits owing to the low statistical power and few reported interactions to date. to address this issue, the Gene-Lifestyle Interactions Working Group within the Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium has been spearheading efforts to investigate G × E in large and diverse samples through meta-analysis. Here, we present a powerful new approach to screen for interactions across the genome, an approach that shares substantial similarity to the Mendelian randomization framework. We identify and confirm 5 loci …