Digital Commons Network^™

Deep-Learning Endomicroscope With Large Field-Of-View And Depth-Of-Field For Real-Time In Vivo Imaging Of Epithelial Cancer Hallmarks, Huayu Hou, Jimin Wu, Jinyun Liu, Vivek Boominathan, Argaja Shende, Karthik Goli, Jennifer Carns, Richard A Schwarz, Ann M Gillenwater, Preetha Ramalingam, Mila P Salcedo, Kathleen M Schmeler, Tomasz S Tkaczyk, Jacob T Robinson, Ashok Veeraraghavan, Rebecca R Richards-Kortum

Faculty, Staff and Students Publications

In vivo microscopy (IVM) has shown great promise to improve early detection of epithelial precancer, but it suffers from fundamental trade-offs that limit the resolution, field-of-view (FOV) and depth-of-field (DOF). Here, we present PrecisionView, a compact, deep learning-enabled endomicroscope that breaks these constraints and achieves 20 mm2 FOV and 500 µm DOF with 4 µm resolution, representing approximately 5× increase in FOV and 8× larger DOF compared to conventional IVM with similar resolution. PrecisionView integrates a deep learning-optimized phase mask and real-time reconstruction, enabling rapid in vivo assessment of two key hallmarks of cancer: epithelial cell nuclear morphology and subsurface …

Investigating Racial Differences In The Receipt Of Antenatal Interventions Prior To Periviable Delivery, Niurka Monteserin, Whitney Bender

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: The Society for Maternal Fetal Medicine (SMFM) provides guidance on the use of antenatal corticosteroids, antibiotics, and cesarean delivery in the periviable period. Although racial differences exist in postnatal active management of periviable neonates have been described, less is known about racial differences in antenatal interventions preceding delivery.

OBJECTIVE: To evaluate differences in the receipt of antenatal interventions before periviable delivery by birthing parent race.

METHODS:  We conducted a population-based cohort study using the National Center for Health Statistics database including periviable deliveries (20w0d-25w6d) from 2016-2021. Individuals delivering a non-anomalous live singleton gestation in a hospital were included. Births …

Urobiome Composition Varies With Vesicoureteral Reflux Grade And History Of Febrile Urinary Tract Infection, Theresa C. Barrett, Kelvin Li, Adam Fitch, Asha Patel, Bhanu Sharma, Jacqueline Holden, Kermina Abdelsayed, Nina N. Kowalewski, Sridhar Narla, Daniel Bushnell, Barbara A. Methé, Catherine S. Forster

Department of Medicine Faculty Papers

Vesicoureteral reflux (VUR) is a risk factor for urinary tract infection (UTI). However, data describing the urobiome in children with VUR are limited. Here, we characterized the urobiome in children with and without VUR to better understand its potential role in VUR pathogenesis. Catheterized urine samples were obtained from children who presented for voiding cystourethrogram (VCUG) between 12/1/2020 and 10/3/2023. Children were excluded if they had any surgical procedures of the genitourinary tract in the 30 days prior to VCUG or were on treatment antibiotics at the time of VCUG. 16S rRNA gene sequencing and taxonomical classification identified the urobiome. …

Pneumomlpred: Innovating Pneumonia Management With Guideline Adherence Review And Explainable Machine Learning-Based Mortality Prediction - A Single-Centre Retrospective Study, Kamel A. Samara, Hiba Jawdat Barqawi, Saryia Adra, Batool Aldaher, Drishti D. Kampani, Enad Haddad, Hebah Soudan, Islam Ibrahim Anwar, Mohamad Besher Adi, Omar Hamadi, Yumna Almour, Mohamed Nassef, Zaher Al Aghbari, Eman Abu-Gharbieh

Abington Jefferson Health Papers

Introduction: Community-acquired pneumonia (CAP) is one of the leading causes of death globally. Changing antibiotic resistance profiles, paucity of reliable CAP mortality prediction models, and ageing populations will increase its burden. This study aims to evaluate adherence to CAP management guidelines as well as develop an ML-based mortality prediction model.

Methods: This retrospective, chart review included all CAP cases between 2016 and 2021. Variables collected included patients' demographics, comorbidities, vitals, laboratory, imaging, and culture findings, as well as initial and targeted antibiotic regimens. Data was pre-processed and analysed in python-3. Adherence to the American thoracic society/infectious diseases society of America …

Subclinical Neuropsychiatric Trait Variation In Parents Of Children With Autism Spectrum Disorder: A Cohort Study, Lindsay J Mullin, Carolyn Lasch, Natasha Marrus, Et Al.

2020-Current year OA Pubs

BACKGROUND: Many neuropsychiatric conditions share overlapping features underpinned by shared genetics. In this study, we examined the co-aggregation of sub-threshold variation in neuropsychiatric phenotypes in biological parents of autistic children to provide insights into the intergenerational transmission of genetic liability for autism.

METHODS: Autistic, neuropsychiatric (i.e., anxiety, depression, ADHD), and cognitive traits were characterized in biological parents of children enrolled in a longitudinal developmental study: 189 families of autistic children and 100 families with no autistic children were included. Families were further characterized as having only one (simplex) or more than one (multiplex) autistic child. Maternal and paternal traits were …

Longitudinal Changes In Cognition And Brain Imaging In Persons With Human Immunodeficiency Virus, James Kennedy, Sarah A Cooley, June Roman Fox, Kalen J Petersen, Elizabeth Westerhaus, Pat Reid, Linet Lopez, Beau M Ances

2020-Current year OA Pubs

BACKGROUND: As persons with human immunodeficiency virus (PWH) live longer, interactions between human immunodeficiency virus (HIV), aging, and structural brain integrity become increasingly vital for understanding cognitive disorders. This study analyzed the effects of aging, HIV serostatus, and viral load on cognition and brain volumes in a large cohort of persons without HIV (PWOH), PWH with undetectable virus (PWHU) (HIV RNA ≤50 copies/mL), and PWH with detectable virus (PHWD) (HIV RNA >50 copies/mL). Cross-sectional and longitudinal data were included.

METHODS: Cognitive composites (NPZ4) and brain volumes were obtained from 259 PWOH, 264 PWHU, and 84 PWHD with a total of …

Vaccination-Related Applications And Health Care Professionals' Observed Changes In Human Papillomavirus Vaccine Hesitancy: Cross-Sectional Survey, Manali Desai, Shreela Sharma, Joel Fokom-Domgue, Robert Yu, Wenyaw Chan, Onyema G Chido-Amajuoyi, Charles Darkoh, Sanjay Shete

Faculty, Staff and Student Publications

Background: Digital tools are known to promote public health interventions such as vaccine delivery. The recommendation that health care professionals (HCPs) use vaccination-related mobile apps or web-based applications has contributed to improving vaccine awareness and acceptance in the United States. The state of Texas, which has one of the lowest human papillomavirus (HPV) vaccination rates, has seen a significant increase in HPV vaccine hesitancy, particularly during the COVID-19 pandemic.

Objective: This study aimed to examine the association between changes in HPV vaccine hesitancy observed by HCPs among patients in Texas and promotion of vaccination-related applications at the health care facilities …

Leveraging Multimodal Large Language Models For Fall Risk Reduction In Older Adults In The Home: Proposed Model Design, Justin Do, Vivaswat Suresh, Lily Zhang, Bharvi M. Chavre, Jeremy Cha, Robert S. Pugliese

SKMC Student Presentations and Publications

This research letter proposes a novel model design leveraging natively multimodal large language models to identify fall risks and generate visualizations of recommended home environmental modifications, aiming to improve the accessibility and impact of personalized fall prevention advice for older adults. Through a pilot rating study, this work demonstrates that multimodal large language models can generate safe and actionable advice to reduce fall risk in lived spaces of older adults, and also generate realistic edits based on original images. While this concept needs further testing and clinical comparison, it highlights a promising avenue for further innovation of fall prevention tactics.

A Survey Of Health Professions Learners’ Attitudes Towards Social Media In Medical Education: A Substance Use Disorders Education Case Study, Gregory A. Jaffe, Sarah Lawson, William Leach, Mallika Kodavatiganti, Erin Avanzato, Katherine Fesperman, Heather Klusaritz

Department of Family & Community Medicine Faculty Papers

BACKGROUND: Social media is a ubiquitous part of the modern world and plays a key role in the dissemination of information. While utilizing social media for educational purposes has been repeatedly demonstrated as feasible, it has been underutilized in medical education and remains a critical opportunity to integrate microlearning and stigma reduction curricula.

METHODS: A cross-sectional survey on social media usage, attitudes, and beliefs was sent to medical and nursing students at two large academic institutions within Philadelphia. Descriptive statistics are reported, and non-parametric tests were utilized for exploratory analyses.

RESULTS: Health learners were low consumers of social media, reporting …

Postapproval Study For Brain-Responsive Neurostimulation For Drug-Resistant Focal Epilepsy: Three-Year Efficacy And Interim Safety Results, Dawn Eliashiv, Vikram R Rao, Barbara C Jobst, Jerzy P Szaflarski, John D Rolston, Lesley C Kaye, Taneeta Mindy Ganguly, Katie Bullinger, Patricia C Dugan, David E Burdette, Angela Y Peters, Atif Sheikh, Kevin F Haas, Dileep R Nair, Lilit Mnatsakanyan, Imran H Quraishi, Meriem K Bensalem-Owen, Rns System Pas Study, Michael J Doherty, Babak Razavi, Tiffany L Fisher, Christopher Skidmore, Pradeep N Modur, Tawnya M Constantino, Vicenta Salanova, Andrew J Cole, Olga Taraschenko, Angelica Rivera-Cruz, James W Wheless, Nitin Tandon, Antoaneta Balabanov, Sami Aboumatar, Itzhak Fried, Cornelia Drees, Hae Won Shin, Zeenat Jaisani, Stephanie E Maciver, Sanjay E Patra, Edward F Chang, Jon T Willie, Ryder Gwinn, Travis Stoub, John M Stern, Tami Crabtree, Cairn G Seale, Sharon C Mcfadden, Jacob F Norman, Lise Johnson, Martha J Morrell

Faculty, Staff and Student Publications

Background and objectives: Neuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct brain stimulation device (The RNS System for focal epilepsy), the Food and Drug Administration required a prospective study to evaluate whether real-world safety and effectiveness differed from outcomes in the RCT.

Methods: This open-labeled study enrolled adult participants who met the RNS System-approved indication for use. The primary effectiveness end point was median percent change in seizure frequency at 3 years of treatment. Interim safety is presented; the primary safety endpoint analysis will …

Multi-Grader Validation Of The Telemedicine Retinopathy Of Prematurity Severity Score, Harrison W. Pratt, Sarthak V. Shah, Cindy S. Zhao, Arthur R. Brant, Caroline R. Baumal, Cagri G. Besirli, Audina M. Berrocal, Kimberley A. Drenser, Anna L. Ells, Clio Armitage Harper, G. Baker Hubbard, Eric D. Nudleman, Polly Quiram, Irena Tsui, Edward Wood, Yoshihiro Yonekawa, Tatiana Rosenblatt, Jochen Kumm, Darius M. Moshfeghi

Wills Eye Hospital Papers

We aimed to statefully validate Retinopathy of Prematurity (ROP) grading by evaluating intergrader variability over age-matched simulated exams. In a prospective retinal photographic grading cohort study, both eyes of twenty patients with five images per eye per visit were graded by twelve expert graders across six weekly visits. For each eye visit, ROP experts graded the Zone, Stage, and Plus, from which the Telemedicine ROP Severity Score (tROP-SS) was calculated. Graders retained knowledge of prior assessments for a given eye and followed International Classification of ROP rules. Intergrader coefficient of variation (CoV) for Zone, Stage, Plus, and tROP-SS remained below …

Postapproval Study For Brain-Responsive Neurostimulation For Drug-Resistant Focal Epilepsy: Three-Year Efficacy And Interim Safety Results, Dawn Eliashiv, Vikram R. Rao, Barbara C. Jobst, Jerzy P. Szaflarski, John D. Rolston, Lesley C. Kaye, Taneeta Mindy Ganguly, Katie Bullinger, Patricia C. Dugan, David E. Burdette, Angela Y. Peters, Atif Sheikh, Kevin F. Haas, Dileep R. Nair, Lilit Mnatsakanyan, Imran H. Quraishi, Meriem K. Bensalem-Owen, Michael J. Doherty, Babak Razavi, Tiffany L. Fisher, Christopher T. Skidmore, Pradeep N. Modur, Tawnya M. Constantino, Vicenta Salanova, Andrew J. Cole, Olga Taraschenko, Angelica Rivera-Cruz, James W. Wheless, Nitin Tandon, Antoaneta Balabanov, Sami Aboumatar, Itzhak Fried, Cornelia Drees, Hae Won Shin, Zeenat Jaisani, Stephanie E. Maciver, Sanjay E. Patra, Edward F. Chang, Jon T. Willie, Ryder Gwinn, Travis Stoub, John M. Stern, Tami Crabtree, Cairn G. Seale, Sharon C. Mcfadden, Jacob F. Norman, Lise Johnson, Martha J. Morrell

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Neuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct brain stimulation device (The RNS System for focal epilepsy), the Food and Drug Administration required a prospective study to evaluate whether real-world safety and effectiveness differed from outcomes in the RCT.

METHODS: This open-labeled study enrolled adult participants who met the RNS System-approved indication for use. The primary effectiveness end point was median percent change in seizure frequency at 3 years of treatment. Interim safety is presented; the primary safety endpoint analysis will …

Smart Pediatric Oncology Tracker Of Symptoms (Spots), A Web-Based Interface For The Pediatric Pro-Ctcae: Development And Usability Study, Stacey Crane, Deevakar Rogith, Melody Hellsten, Andrew D Miller, Jacqueline Castillo, Brandy Boeger, Susan Vidaurre, Stefanie Pieper, Cecile Nguyen, Duc Anh Thanh Huynh, Jessica Wooden, Amy Franklin, Karen Moody, Wenyaw Chan, Pamela S Hinds, Constance Johnson

Faculty, Staff and Student Publications

Background: Children undergoing cancer treatment experience a range of treatment-related toxicities that significantly affect quality of life and adherence to therapy. Current methods for symptom reporting rely heavily on clinician interpretation of caregiver or child verbal reports, which can result in incomplete or inaccurate records. The Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Pediatric PRO-CTCAE; National Cancer Institute) provides a validated mechanism for direct symptom reporting by children and caregivers, yet its traditional administration and preselection of questions limit the breadth of symptom capture.

Objective: This research aimed to co-design and conduct formative usability testing …

Simultaneous Multielectrode Recordings Along The Human Scala Tympani: Evidence For Level-Dependent Place Coding, Amit Walia, Matthew A Shew, Shannon M Lefler, Amanda J Ortmann, Patrick Ioerger, Jordan Varghese, Jacques A Herzog, Craig A Buchman

2020-Current year OA Pubs

The cochlea systematically encodes sound frequency and intensity via a precisely organized tonotopic map, in which traveling waves peak at specific cochlear locations. A fundamental but incompletely understood aspect of auditory coding involves how stimulus intensity shapes this tonotopic organization. In animal models, increasing intensity shifts the cochlear traveling wave peak basally; however, physiological evidence for such intensity-dependent shifts in human cochlear processing is limited. Here, we performed simultaneous multielectrode electrocochleography recordings along the human scala tympani to characterize how cochlear place coding varies as a function of stimulus intensity. In subjects with preserved cochlear mechanics, including individuals with auditory …

Mosunetuzumab Monotherapy Is Active And Tolerable In Patients With Relapsed/Refractory Richter Transformation, Katharine L Lewis, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

Richter transformation (RT) to diffuse large B-cell lymphoma is an aggressive lymphoma that arises from underlying chronic lymphocytic leukemia or small lymphocytic lymphoma. RT is often chemorefractory, resulting in poor clinical outcomes with standard chemoimmunotherapy. Mosunetuzumab, a bispecific CD20/CD3 T-cell-engaging antibody, was investigated in a cohort of 20 patients with relapsed/refractory RT. Cytokine release syndrome occurred in 65% of patients, almost exclusively grade 1 (20%) or grade 2 (40%), and occurring during the first treatment cycle. Other adverse events included infections, neutropenia, thrombocytopenia, tumor flare, and low-grade neurotoxicity, with no adverse events leading to treatment discontinuation. Mosunetuzumab resulted in an …

The Hidden Crisis: A Rare Case Of Thyrotoxicosis In A Young Female, Mimicking Neuromuscular Disease, Ali Haider Awan, Seerat Riaz, Hafiz Muhammad Hashim Butt, Sajeela Riaz, Fnu Sameeha, Hilana Soliman Omar, Shafia Naeem, Abida Perveen, Jahanzeb Malik

Journal of Community Hospital Internal Medicine Perspectives

Thyrotoxic periodic paralysis (TPP) is a rare but life-threatening cause of acute flaccid paralysis associated with hypokalemia. Although more common in males and individuals of Asian descent, it may present atypically in young females and be easily misdiagnosed. We report a case of a 30-year-old female who presented with acute quadriparesis. Extensive neuromuscular evaluation initially pointed toward Guillain-Barré syndrome (GBS), but subsequent investigations revealed profound hypokalemia. Further workup confirmed thyrotoxicosis as the underlying cause. Prompt potassium replacement and initiation of antithyroid therapy led to complete clinical recovery. This case highlights the importance of considering both endocrine disorders and electrolyte disturbances, …

Natural History Of Ngly1 Deficiency: Motor Function & Clinical Features, Grace Morrison, Selina Dwight, Hal Landy, William F Mueller, Pam Ventola, Regina Deck, Becky Schweighardt, Matt Wilsey, Kevin J Lee, Bernhard Suter

Faculty, Staff and Students Publications

N-glycanase 1 (NGLY1) Deficiency is an ultra-rare neurodevelopmental disorder caused by biallelic loss-of-function mutations in the NGLY1 gene, leading to severe impairments in neurocognitive and motor function abilities in the affected patient population. Its core clinical features include global developmental delay, hyperkinetic movement disorders, elevation of liver transaminases, (hypo)alacrima, and progressive sensorimotor neuropathy. Due to the range of phenotypes and severity within the confirmed patient population, ongoing characterization of the disease is critical. A prospective natural history study (NHS) was conducted to further elucidate disease phenotypes and examine any changes in neurocognitive or motor function over a one-year period. Fifteen …

Risk Of Late Recurrence Of Colorectal And Breast Cancer Among Older Long-Term Cancer Survivors., Faiza Yasin, Sarah J. Westvold, Jessica B. Long, Terry Hyslop, Michael Cecchini, Ira Leeds, Andrea Silber, Shi-Yi Wang, Lisa Spees, Rebecca Forman, Tendai Kwaramba, Melissa Taylor, Cary P. Gross, Michaela A. Dinan

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

BACKGROUND: A growing population of older adult cancer survivors faces competing cancer and noncancer health risks. There are limited real-world data on recurrence patterns beyond 5 years post-treatment.

METHODS: This was a SEER-Medicare retrospective cohort study of patients aged ≥66 with stage I-III breast, colon, or rectal cancer who received definitive surgery and survived ≥5 years from diagnosis without recurrence or second primary malignancy. Late recurrence (5-10 years postdiagnosis) was identified using a validated algorithm to detect treated recurrence in Medicare claims. Demographic and clinical characteristics collected at cancer diagnosis were assessed as predictors of late treated recurrence using restricted …

Developmental Origins Of Exceptional Health And Survival: A Four-Generation Family Cohort Study, Matthew Thomas Keys, Søren Netra, Dorthe Almind Pedersen, Pernille Stemann Larsen, Alexander Kulminski, Mary F Feitosa, Mary Wojczynski, Michael Province, Kaare Christensen

2020-Current year OA Pubs

Descendants of longevity-enriched sibships demonstrate a broad health and survival advantage throughout the life course. However, little is known about manifestations during very early life. Here we show a pattern of lower risk of adverse early-life outcomes in third-generation grandchildren (N = 5637) of Danish longevity-enriched sibships compared to the general population, including infant mortality (Hazard Ratio = 0.53, 95% CI [0.36, 0.77]) and a range of neonatal health indicators. These associations in fourth-generation great-grandchildren (N = 14,908) were attenuated and less consistent (e.g., infant mortality, Hazard Ratio = 0.90, [0.70, 1.17]). Dilatory patterns across successive generations were independent of …

Inflammatory Markers In The Emergency Department And Ptsd Symptoms In The Aurora Study: A Longitudinal Cohort Study, Kristen Nishimi, Sarah Linnstaedt, Thomas Neylan, Lauren Mckibben, Liz Marie Albertorio-Sáez, Ying Zhao, Stacey House, Francesca Beaudoin, Xinming An, Jennifer Stevens, Gari Clifford, Tanja Jovanovic, Laura Germine, Scott Rauch, John Haran, Alan Storrow, Paul Musey, Phyllis Hendry, Sophia Sheikh, Brittany Punches, Robert Swor, Jose Pascual, Mark Seamon, Elizabeth M Datner, Claire Pearson, David Peak, Roland Merchant, Robert Domeier, Niels Rathlev, Brian O'Neil, Paulina Sergot, Leon Sanchez, Steven Bruce, Steven Harte, Ronald Kessler, Karestan Koenen, Kerry Ressler, Samuel Mclean, Aoife O'Donovan

Department of Emergency Medicine Faculty Papers

BACKGROUND: Systemic inflammation is hypothesized to contribute to post-traumatic stress disorder (PTSD) vulnerability. Few studies have examined inflammation shortly after trauma as a predictor of later PTSD symptoms. We examined whether inflammation from the emergency department (ED) post-trauma is associated with PTSD symptom severity over the following 6 months.

METHODS: Our sample included 742 AURORA participants, a longitudinal cohort of patients in 29 EDs across the United States after a traumatic stressor, followed up to 6 months. Plasma cytokines were assessed from a study blood draw in the ED: an inflammatory index (standardized sum of generally pro-inflammatory markers interleukin [IL]-6, …

Inflammatory Markers In The Emergency Department And Ptsd Symptoms In The Aurora Study: A Longitudinal Cohort Study, Kristen Nishimi, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: Systemic inflammation is hypothesized to contribute to post-traumatic stress disorder (PTSD) vulnerability. Few studies have examined inflammation shortly after trauma as a predictor of later PTSD symptoms. We examined whether inflammation from the emergency department (ED) post-trauma is associated with PTSD symptom severity over the following 6 months.

METHODS: Our sample included 742 AURORA participants, a longitudinal cohort of patients in 29 EDs across the United States after a traumatic stressor, followed up to 6 months. Plasma cytokines were assessed from a study blood draw in the ED: an inflammatory index (standardized sum of generally pro-inflammatory markers interleukin [IL]-6, …

Nudging Implementation Of Low Tidal Volume Ventilation: A Stepped Wedge, Cluster Randomized Trial, Meeta Prasad Kerlin, Michael O. Harhay, Fan Li, Dylan S. Small, Yingying Lu, Wei Wang, Barry D. Fuchs, Mark E. Mikkelsen, Teresa Tran, Aerielle Belk, Jasmine A. Silvestri, Tamar Klaiman, Stefania Scott, Elizabeth Levy, Michael W. Sjoding, Rachel Kohn, Karsten J. Roberts, Rinad S. Beidas, Scott D. Halpern

College of Health Professions Faculty Papers

BACKGROUND: "Nudges" embedded in the electronic health record (EHR) facilitate desired decisions while preserving autonomy and may provide a scalable strategy to overcome the common implementation barrier of lack of knowledge about a best practice. We sought to test whether EHR-based nudges targeting two intensive care unit (ICU) clinician groups would safely increase evidence-based use of low tidal volume ventilation.

METHODS: We performed a stepped-wedge, cluster randomized, hybrid type 3 effectiveness-implementation trial in 12 ICUs from February 2021 to May 2023 to test three nudges targeting clinicians responsible for order entry and respiratory therapists responsible for operationalizing orders and documentation. …

Systemic Α₂-Agonist Use And Lower Hazard Of Glaucoma Compared With Β-Blockers: A Cohort Study, Ibrahim Abboud, Amin Z. Khudari, Abdelaziz Abdelaal, Amr Almobayed, Subhi J. Al'aref, Jonathan S. Myers, Richard K. Lee, Abdelrahman M. Elhusseiny

Wills Eye Hospital Papers

OBJECTIVE: Systemic antihypertensive medications may influence glaucoma-related outcomes through intraocular pressure-dependent and vascular mechanisms. While topical α₂-agonists are established glaucoma therapies, the association between systemic α₂-agonists and glaucoma hazard remains unexamined; we compared their hazard with systemic β-blockers in adults with hypertension.

METHODS AND ANALYSIS: We conducted a multicentre retrospective cohort study using deidentified electronic health records. Adults aged ≥40 years with hypertension and chronic exposure to systemic α₂-agonists or β-blockers were included. Patients with pre-existing ocular hypertension (OHT), primary open-angle glaucoma (POAG), concomitant comparator use, or inadequate ophthalmic follow-up were excluded. We balanced cohorts using propensity score matching (PSM) …

Pharmacogenomic-Guided Prescribing And Polypharmacy Across Age Groups In Obsessive-Compulsive Disorder: A Retrospective Study, Sheldon R Garrison, Matthew W Boyer, Anthony W Zoghbi, Rachel A Schwartz, Nicolette Weisensel, Martin E Franklin, Madeline M Hartig, Maharaj Singh, Sreya Vadapalli

Faculty, Staff and Students Publications

Background: This study evaluated medication utilization in children, adolescents, and adults with obsessive-compulsive disorder (OCD), a chronic psychiatric condition characterized by intrusive thoughts and repetitive behaviors. Although first-line treatments include selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT), the heterogeneous biological underpinnings contribute to suboptimal outcomes, with 40-60% of individuals not responding to SSRIs. This complex phenotype often leads to psychotropic polypharmacy, which may be mitigated by incorporating combinatorial pharmacogenomic (PGx) testing into protocol-based care to identify potential gene-drug interactions.

Methods: A retrospective review was conducted of individuals with OCD aged 8 to 65 years who received either …

Genetic Analysis Of The X-Linked Adrenoleukodystrophy Gene Abcd1 In Drosophila Uncovers A Conserved Phenotype, Joshua Manor, Sharayu V Jangam, Hyung-Lok Chung, Pranjali Bhagwat, Jonathan C Andrews, Hillary Chester, Shu Kondo, Saurabh Srivastav, Juan Botas, Ann B Moser, Suzette M Huguenin, Michael F Wangler

Duncan NRI Faculty and Staff Publications

X-linked adrenoleukodystrophy (X-ALD) is a progressive neurodegenerative disorder caused by a loss-of-function (LOF) mutation in the ATP-binding cassette subfamily D member 1 (ABCD1) gene, leading to the accumulation of very long-chain fatty acids (VLCFAs). This disorder exhibits striking heterogeneity; some male patients develop an early childhood neuroinflammatory demyelination disorder, while other patients, including adult males and most affected female carriers, experience a chronic progressive myelopathy. Adrenocortical failure is observed in almost all male patients, with the age of onset varying, sometimes being the first diagnostic finding. The gene underlying this spectrum of disease encodes an ATP-binding cassette (ABC) transporter that …

+Cd49a+Cd103+ Cytotoxic Tissue-Resident Natural Killer Cells Infiltrate And Control Solid Epithelial Tumor Growth In Mice, Nina B Horowitz, Jennifer A Foltz, Et Al.

2020-Current year OA Pubs

Human tissue-resident natural killer (NK) cells (trNK cells), broadly defined by markers of tissue residency, such as CD49a [

Early-Life Wnt4 Expressing Colon Stromal Cells Orchestrate Lifelong Mucosal Homeostasis Via Bmp-Driven Inkt Cell Imprinting, Xi Lin, Chloe Hyun-Jung Lee, Ting Zhang, Agne Antanaviciute, Thomas Hanley, Jonathan N Glickman, Nikhila S Bharadwaj, Vicki Rosen, Jenny E Gumperz, Matthew K Waldor, Alison Simmons, Thomas Gensollen, Richard S Blumberg

2020-Current year OA Pubs

The early-life intestinal microenvironment plays a pivotal role in shaping immune cell development. Here, we identify a colonic Wnt4-expressing stromal cell, enriched during early-life, that promotes iNKT cell proliferation via BMP-MAPK signaling. These stromal cells are spatially associated with iNKT cells and macrophages and exhibit high Bmp2 expression during the neonatal period. Depletion of BMP2 in Wnt4

Apathy, Effort-Based Decisions And Brain Integrity In Alzheimer’S And Parkinson’S Diseases, Lee-Anne Morris, Hideo Suzuki, Seonjoo Lee, Zekai Jin, Bryan B Chen, Ana Marin, Edward D Huey, Yunglin Gazes, Sarah R Heilbronner, Campbell J Le Heron, Nora Vanegas-Arroyave

Faculty, Staff and Students Publications

Apathy, or loss of motivation, is a prominent syndrome accompanying both Alzheimer's and Parkinson's diseases, in addition to other disorders. One approach to understanding motivational loss is to examine the processes underlying goal-directed behaviour. Weighing up rewarding outcomes against the effort costs required to obtain them (effort-based decision-making) is a core computation when deciding to act for outcomes. Although a growing body of evidence points to disruption of this computation in people with apathy, which underlying decision parameters drive this disruption, their neural associations and whether these would generalize or differ across brain disorders have not been examined. People with …

Large-Scale Genetic Characterization Of Parkinson's Disease In The African And African Admixed Populations, Fulya Akçimen, Scott A Norris, Erin R Foster, Et Al.

2020-Current year OA Pubs

Elucidating the genetic contributions to Parkinson's disease aetiology across diverse ancestries is a critical priority for the development of targeted therapies in a global context. We conducted the largest sequencing characterization of potentially disease-causing, protein-altering and splicing mutations in 710 cases and 11 827 controls from genetically predicted African or African admixed ancestries. We explored copy number variants (CNVs) and runs of homozygosity in prioritized early onset and familial cases. Our study identified rare GBA1 coding variants to be the most frequent mutations among patients with Parkinson's disease, with a frequency of 4% in our case cohort. Of the 18 …

Transcriptome Predictors Of Second Breast Events In Ductal Carcinoma In Situ: A Case‒Control Study Including Black And White Women, Aditi Hazra, Emma Berdan, Thomas Walsh, Sarah Humble, Jen Tappenden, Katherine Deschryver, Deborah Veis, Kiran Vij, Shannan Ho Sui, Graham A Colditz

2020-Current year OA Pubs

BACKGROUND: Black women diagnosed with ductal carcinoma in situ (DCIS) experience disproportionately higher risk of second breast cancer events (SBEs), including both ipsilateral and contralateral recurrences, yet remain underrepresented in molecular biomarker studies compared to non-Hispanic White women.

METHODS: We performed RNA sequencing on 200 archival DCIS samples from the Resource of Archival Breast Tissue cohort, including 33% self-reported Black women. We correlated transcriptomic and clinical data to identify predictors of SBEs. Cases (n = 100) who developed SBEs between 1999 and 2019 were matched 1:1 to controls (n = 100) on age, race, and margin status, who remained event-free …