Medicine and Health Sciences Commons^™

Human Cerebral Organoids Model Tumor Initiation And Infiltration In An Autologous Astrocyte-Supported Setting, Esther Schickel, Tamara Bender, Leon Kaysan, Simone Hufgard, Margot Mayer, David R Grosshans, Christiane Thielemann, Insa S Schroeder

Faculty, Staff and Student Publications

Efforts to efficiently target brain tumors are constrained by the dearth of appropriate models to study tumor behavior toward treatment approaches as well as potential side effects to the surrounding normal tissue. We established a reproducible cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing

Metabolic Shifts In Murine Inner Ears Mimicking Erythrocytes And Plasma Reveal Diagnostics And Early Predictors For Age-Related Hearing Loss, Qi Guo, Zhenjiang Li, Cheng Luo, Changhan Chen, Xi Long, Yidan Wang, Qingfen Qiang, Fang Yu, Wuping Liu, Yujin Zhang, Rodney E Kellems, Yang Xia

Faculty, Staff and Student Publications

Age-related hearing loss (ARHL) is a major public health concern, driven by the interplay of multiple factors. Here, we reveal spatiotemporal metabolic shifts in murine inner ears mirroring erythrocytes and plasma. Isotope-labeled glucose tracing demonstrates a metabolic rerouting favoring glycolysis over the pentose phosphate pathway, alongside downregulation of the tricarboxylic acid cycle, indicating impaired energy production and redox homeostasis. Accumulation of medium- and long-chain acylcarnitines further exacerbates lipotoxicity. Notably, age-dependent depletion of arginine, lysine, proline, and glycine disrupts the arginine-polyamine-urea cycle. Translationally, UK Biobank plasma metabolomics links omega-6 fatty acids, linoleic acid, glycine, and albumin to ARHL resilience, while branched-chain …

Ethical Issues Involved In Solid Organ Xenotransplantation., Daniel J Hurst, Chris Bobier, Luz A Padilla

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Xenotransplantation (specifically, genetically modified pig-to-human transplant of organs, tissues, or cells) clinical trials are set to begin in the United States after decades of pre-clinical studies and recent decedent and compassionate use investigations. This article provides a primer on the key ethical issues attendant with this emerging therapy. We explore four central areas of concern: (i) the use of animals to meet human transplant needs, as well as their welfare since they are housed in non-natural conditions, (ii) the risk of infectious disease transfer from the porcine graft to the human recipient, known as xenozoonosis, (iii) patient selection criteria for …

Efficacy And Safety Of Rigosertib In Patients With Recessive Dystrophic Epidermolysis Bullosa-Associated Advanced/Metastatic Cutaneous Squamous Cell Carcinoma, Martin Laimer, Andrew P. South, Elisabeth Mayr, Sophie Kitzmueller, Lauren Banner, Michael Alexander, Linda Hosler, Henry Yang, Matthew Parris, Meena Arora, Georg Zimmermann, Gregor Schweighofer-Zwink, Johann Bauer, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is an epithelial fragility disease primarily affecting the skin and is caused by variants in the COL7A1 gene. Individuals with RDEB are predisposed to develop highly aggressive cutaneous squamous cell carcinomas (SCCs) which are the most common cause of premature death. There is a lack of effective prevention or treatment options for patients with RDEB-SCC.

OBJECTIVES: To evaluate the antitumour activity and safety of the polo-like kinase-1 (PLK1) inhibitor, rigosertib, two investigator-initiated open-label, single-arm phase II studies were opened in Europe and the USA and enrolled five patients with RDEB diagnosed with locally advanced …

Clinical Pharmacokinetics, Pharmacodynamics, And Drug Interactions Of Remimazolam, Derek E. Murrell, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Remimazolam, an ultrashort-acting benzodiazepine, has emerged as a promising sedative agent for procedural sedation and general anesthesia. It combines the favorable properties of traditional benzodiazepines with a rapid onset and offset of action, largely due to its unique metabolism via hepatic carboxylesterases rather than cytochrome P450 enzymes. This metabolism allows for predictable pharmacokinetics, reducing the risk of prolonged sedation and drug accumulation, particularly in patients with hepatic or renal impairment. Clinically, remimazolam demonstrates non-inferiority to midazolam and propofol, with advantages including a lower incidence of hypotension and respiratory depression. Multiple randomized controlled trials have shown its efficacy in various procedural …

A Case Study Of Long-Term Disease Burden In A Rural Community Near An Open Burn Facility, Arundhati Bakshi, Liana Baconguis, Md Abdullah Al-Mamun, Qingzhao Yu, Jennifer Richmond-Bryant, Stephania A. Cormier

School of Public Health Faculty Publications

Open burning and open detonation (OB/OD) of explosive and hazardous wastes creates various toxic waste products, including particulate matter, that is released into the atmosphere and capable of generating significant health impacts upon exposure. The last commercially run OB/OD thermal treatment facility in operation in the United States is located near the rural community of Colfax in central Louisiana. To evaluate the community’s concerns about the potential health impacts from air pollution due to the facility’s regular open burning of explosive and hazardous wastes, we examined the disease burden in Colfax compared to the surrounding parish and state. In a …

Can Handoffs Bridge The Interprofessional Divide To Build A Team?, Aubrey Samost-Williams, Eric J Thomas

Faculty, Staff and Student Publications

No abstract provided.

Integrated Mirna-Mrna Analyses Of Triple-Negative Breast Cancer In Black And White Patients With Or Without Obesity, Fokhrul Hossain, Martha I. Gonzalez-Ramirez, Jone Garai, Diana Polania-Villanueva, Li Li, Farzeen Nafees, Md Manirujjaman, Bolin Liu, Samarpan Majumder, Xiao Cheng Wu, Chindo Hicks, Luis Del Valle, Denise Danos, Augusto Ochoa, Lucio Miele, Jovanny Zabaleta

School of Graduate Studies Faculty Publications

Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous subtype of breast cancer. miRNAs play an essential role in TNBC pathogenesis and prognosis. Obesity is linked with an increased risk for several cancers, including breast cancer. Obesity is also related to the dysregulation of miRNA expression in adipose tissues. However, there is limited knowledge about race- and obesity-specific differential miRNA expression in TNBC. We performed miRNA sequencing of 48 samples (24 tumor and 24 adjacent non-tumor tissues) and RNA sequencing of 24 tumors samples from Black (AA) and White (EA) TNBC patients with or without obesity. We identified 55 miRNAs exclusively …

Dementia As A Critical Lens On The Role Of Narrative In Medical Training And Practice, Erin Gentry Lamb

Faculty Scholarship

Narrative holds an important place within medicine and medical education, but an uncritical use of narrative can have troubling consequences for the care of patients who have limited or no capacity for self-narration, such as those living with dementia. We argue that the guiding principles in the use of narrative within medicine and medical education must be inclusivity and opportunity. We illustrate how medical training can benefit from a more inclusive definition of narrative, and we present a selection of innovative approaches to narrative coming out of literary studies, narrative gerontology, and medical and health humanities that focus on metaphor, …

Rapid Mapping Of Spinal And Supraspinal Connectome Via Self-Targeting Glucose-Based Carbon Dots, Yasin B. Seven, Elif S. Seven, Emel Kirbas Cilingir, Komal Parikh, Mehmet Aydin, Edward K. Luca, Jayakrishnan Nair, Roger M. Leblanc

Department of Physical Therapy Faculty Papers

The spinal cord is a highly dynamic network, playing significant roles in the vital functions of the brain. Disorders of the spinal cord, such as spinal cord injury and amyotrophic lateral sclerosis (ALS), are associated with neurodegeneration, often resulting in morbidity and mortality. The blood-brain barrier (BBB) poses a major challenge to imaging and therapeutic agents because less than 2% of small-molecule drugs and almost no large-molecule drugs can cross the BBB. Furthermore, spatial spectroscopy studies have shown highly heterogeneous BBB crossing with significant accumulation at the unintended brain regions. Thus, targeting systems that can cross the BBB at the …

Editorial: Wearable Technology: The New Ornament Of Network Physiology, Ankita Srivastava, Santosh Kumar Yadav

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Introduction: The landscape of personal health monitoring is rapidly transforming, driven by advances in wearable technology. These devices, designed to be worn comfortably on the body, can capture real-time physiological data often difficult to obtain in traditional clinical settings. What began as a simple device for activity trackers for walking steps, heart rate, and blood oxygen saturation has evolved to play a crucial role in monitoring more complex physiological parameters critical for chronic disease management and preventative health.

The integration of artificial intelligence (AI) is further expanding the potential of wearable devices, enabling deeper analysis and predictive modeling of the …

Perceived Knowledge And Confidence Of Beta-Lactam Allergy Management Among Pharmacy Students On Advanced Pharmacy Practice Experiences., Jamie L Wagner, David R Oliver, Bruce M Jones, Kayla R Stover, Misha T Watts, Wesley D Kufel, Lena Mcdowell, Edo-Abasi U. Mcgee, T Lynn Stevenson, Christopher M Bland

PCOM Scholarly Works

Pharmacist engagement in allergy clarification has demonstrated increased appropriate antibiotic use. The purpose of this study was to determine the knowledge and confidence of pharmacy students in their final professional year regarding beta-lactam (BL) allergies. Students from 5 schools of pharmacy participated in a 22-question survey pertaining to experience with drug allergies, knowledge of BL allergies, and confidence regarding BL allergy management. Data were summarized among all respondents and further analyzed by infectious disease (ID) interest. A total of 160/521 students responded to the survey (31%). Most students (73%) had no course dedicated to drug allergies; however, 84% indicated the …

The Impact Of Foraminotomy On Patient-Reported Outcomes Following 3+ Level Posterior Cervical Decompression And Fusion For Myeloradiculopathy, Robert J. Oris, Jonathan Dalton, Joydeep Baidya, Tariq Z. Issa, Tyler D. Alexander, Jarod Olson, Rachel Huang, Chloe Herczeg, Omar Tarawneh, Rajkishen Narayanan, Michael Carter, Jonah Hammerstedt, Sebastian Quiana, Mark Kurd, Barrett I. Woods, I David Kaye, Thomas Cha, Jose A Canseco, Alan S. Hilibrand, Alex R. Vaccaro, Christopher K. Kepler, Gregory D. Schroeder

Department of Orthopaedic Surgery Faculty Papers

OBJECTIVE: To evaluate whether patients with myeloradiculopathy experience better improvement in patient-reported outcome measures (PROMs) from the addition of foraminotomy in the setting of posterior cervical decompression and fusion (PCDF).

METHODS: Adult patients who underwent ≥≥ 3-level PCDF (2017-2022) at a single tertiary center were retrospectively identified. Patients were included if their indication was myeloradiculopathy - patients were excluded if they had a combined anterior/posterior approach, an indication of infection/tumor/trauma, or incomplete 1-year PROMs. Operative notes were evaluated to identify the patients who had a foraminotomy specifically for neuro-decompression. Patients with or without foraminotomy were evaluated for demographic/surgical variables, surgical …

The Impact Of Cage Position, Radiographic Parameters, And Hounsfield Units On Subsidence Rate After One To Three Level Anterior Cervical Discectomy And Fusion, Jarod Olson, Jonathan Dalton, Omar H. Tarawneh, Rajkishen Narayanan, Alec Giakas, Rachel Huang, Joydeep Baidya, Robert J. Oris, Joshua Mathew, William A. Green, Nicholas B. Pohl, Anthony Labarbiera, Benjamin Crain, Nathaniel Pineda, Joseph Rajasekaran, Gordon Hua, Mark F. Kurd, Jeffrey A. Rihn, Jose A. Canseco, Alan S. Hilibrand, Alex R. Vaccaro, Christopher K Kepler, Gregory D. Schroeder

Department of Orthopaedic Surgery Faculty Papers

STUDY DESIGN: The study design was a retrospective cohort.

OBJECTIVE: The objective of the study was to validate the relationship between Hounsfield units (HU) and subsidence, including multilevel anterior cervical discectomy and fusion (ACDF). Cage/graft subsidence commonly occurs after ACDF. Prior work on 1-level ACDF found increased subsidence rates in patients with lower HUs.

MATERIALS AND METHODS: Adults who underwent 1-3 level ACDF at a tertiary center and had preoperative computed tomography scans were included (2018-2022). HUs were assessed ~5 mm caudal to the superior endplate. Six-month postoperative radiographs were evaluated for cage/graft positioning, screw loosening, and subsidence. Receiver operating …

Cetuximab Increases Lgr5 Expression And Augments Lgr5-Targeting Antibody-Drug Conjugate Efficacy In Patient-Derived Colorectal Cancer Models, Peyton C High, Zhengdong Liang, Cara Guernsey-Biddle, Shraddha Subramanian, Yueh-Ming Shyu, Adela M Aldana, Yukimatsu Toh, Kendra S Carmon

The Brown Foundation: Institute of Molecular Medicine

Colorectal cancer (CRC) remains the second-leading cause of cancer-associated deaths, indicating an urgent need for improved therapeutic options. We previously generated antibody-drug conjugates (ADCs) targeting the cancer stem-like cell marker leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5). However, tumor relapse due to LGR5 downregulation and suboptimal payload selection warrants strategies to improve ADC efficacy. Here, we report that cetuximab, an epidermal growth factor receptor (EGFR)-targeting monoclonal antibody indicated for RASWT metastatic CRC, augments LGR5 expression independent of RAS/PIK3CA mutation status and promotes EGFR-LGR5 interactions. Furthermore, we describe the development of LGR5 ADCs incorporating a camptothecin-derived payload that is well tolerated …

Development Of A Novel Algorithm For Tip Fold-Over Detection In Cochlear Implants And Evaluation On Bench And Multiple Clinical Data Bases, Mehrangiz Ashiri, Tony Spahr, Azret Botash, Ashish Mehta, Jordan J Varghese, Craig A Buchman, Andrea J Defreese, Patrick Boyle, Matthew Miller, Syed F Ahsan, Christopher Danner, Kyle P Allen, Loren Bartels, Kanthaiah Koka

2020-Current year OA Pubs

No abstract provided.

Disparities In Liver Transplantation For Metabolic Dysfunction-Associated Steatohepatitis-Associated Hepatocellular Carcinoma, David W Victor, Sudha Kodali, Mazen Noureddin, Elizabeth W Brombosz, Analisa Lopez, Tamneet Basra, Edward A Graviss, Duc T Nguyen, Ashish Saharia, Ashton A Connor, Maen Abdelrahim, Yee Lee Cheah, Caroline J Simon, Mark J Hobeika, Constance M Mobley, R Mark Ghobrial

Faculty, Staff and Students Publications

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly common, as is hepatocellular carcinoma (HCC) in the background of MASH. Liver transplantation (LT) provides superior long-term survival for patients with unresectable MASH-HCC, but not all patients have equal access to transplant. MASH-HCC disproportionately affects Hispanic patients, but minorities are less likely to undergo LT for HCC. Additionally, females also undergo LT at lower rates than males.

Aim: To investigate whether race/ethnicity and sex affect LT waitlist outcomes.

Methods: Records of adults with MASH-HCC in the United States Organ Procurement and Transplantation Network database listed for LT between 1/2015 and 12/2021 were analyzed. …

Rat Somatic Genome Editing Enables Er+ Breast Cancer Modeling, Wen Bu, Tobie Lee, Meenakshi Anurag, Yunfeng Ding, Ruixin Xu, Lillian He, Alexandria Z Bu, Chandandeep Nagi, Carolina Gutierrez, Susan Hilsenbeck, Chonghui Cheng, Bing Zhang, Shixia Huang, Jianming Xu, C Kent Osborne, Arun Sreekumar, Eric Chang, Chad J Creighton, Xiang Zhang, Yi Li

Faculty, Staff and Students Publications

Genetically engineered mouse models have advanced cancer research but often fail to capture key features of certain human tumors. Rats, with distinct physiology and tumor biology, offer a powerful alternative, yet their use has been constrained by technical barriers to genome editing. Here, we report efficient somatic genome editing in rats, enabling both Indel and substitution mutations. We then apply this approach to model estrogen receptor (ER)-positive breast cancer, which accounts for ~70% of human cases but remains poorly represented in mice. The resulting rat tumors reproduce hallmarks of human ER+ breast cancer, including ductal histology, hormone responsiveness, and immune-microenvironmental …

Connecting Innovation And Trust Through Translational Sciences – A Need For A Community Focus And Effective Education Strategiess, Filipa Godoy-Vitorino, Michelle Borrero, Josué Pérez-Santiago, Rubén García-García, Candelaria Gomez-Manzano

Faculty, Staff and Student Publications

Report of a conference held in Puerto Rico, this article highlights how interdisciplinary translational science-anchored in education, public trust, and equity-can accelerate innovation in cancer therapy while empowering underserved communities through inclusive training, collaboration, and research participation.

Allosteric Control Overcomes Steric Limitations For Neutralizing Antibodies Targeting Conserved Binding Epitopes Of The Sars-Cov-2 Spike Protein: Exploring The Intersection Of Binding, Allostery, And Immune Escape With A Multimodal Computational Approach, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Understanding the atomistic basis of multi-layer mechanisms employed by broadly reactive neutralizing antibodies of the SARS-CoV-2 spike protein without directly blocking receptor engagement remains an important challenge in coronavirus immunology. Class 4 antibodies represent an intriguing case: they target a deeply conserved, cryptic epitope on the receptor-binding domain yet exhibit variable neutralization potency across subgroups F1 (CR3022, EY6A, COVA1-16), F2 (DH1047), and F3 (S2X259). The molecular basis for this variability is not fully understood. Here, we employed a multi-modal computational approach integrating atomistic and coarse-grained molecular dynamics simulations, binding free energy calculations, mutational scanning, and dynamic network analysis to elucidate …

Early Blood Pressure Targets In Acute Spinal Cord Injury: A Randomized Clinical Trial, Ruba Sajdeya, N. David Yanez, Michael Kampp, Michael D. Goodman, David Zonies, Brandon Togioka, Andrew Nunn, Robert D. Winfield, Niels D. Martin, Anirudh Kohli, Toan T. Huynh, David O. Okonkwo, Roy A. Poblete, Emily J. Gilmore, Randall M. Chesnut, Aaron E. Bunnell, Tetsu Ohnuma, Mona Hashemaghaie, Miriam M. Treggiari

Department of Surgery Faculty Papers

IMPORTANCE: Early blood pressure management is central to neurologic resuscitation of spinal cord injury; however, the role of augmented blood pressure is unclear.

OBJECTIVE: To compare the efficacy and safety of augmented vs conventional blood pressure on 6-month neurologic outcomes after acute spinal cord injury.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial took place from October 3, 2017, to July 26, 2023, and assessed patients 18 years or older with spinal cord injury followed up for 6 months at 13 large US trauma centers.

INTERVENTIONS: Patients were equally randomized to augmented (>85-90 mm Hg) or conventional ( …

Semilunar Valve Replacement With A Telescoping Arterial Trunk Valve, Edo Bedzra, Herra Javed, James E. O'Brien, Taufiek Konrad Rajab

Manuscripts, Articles, Book Chapters and Other Papers

A bicuspid aortic valve, from autologous tissue, with growth potential can be constructed using the simple, and reproducible telescoping arterial trunk technique.

Obesity Severity And Cancer Screening In Us Adults, Florina Corpodean, Michael Kachmar, Shengping Yang, Michael W. Cook, Philip R. Schauer, Vance L. Albaugh

School of Medicine Faculty Publications

No abstract provided.

Predictors Of All-Cause In-Hospital Mortality In Patients With Malignant Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors, Elvis Obomanu, Tarfa Verinumbe, Tinsae Anebo, Colton Jones, Claudia Dourado

Einstein Health Papers

BACKGROUND: Factors influencing in-hospital mortality in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) remain understudied, highlighting gaps in optimizing acute clinical outcomes. This study aimed to identify sociodemographic and clinical predictors of all-cause in-hospital mortality in this population.

METHODS: Using 2016 - 2020 data from the National Inpatient Sample (NIS), patients with malignant well-differentiated GEP-NETs were identified via the International Classification of Diseases, 10th Revision (ICD-10) codes. The primary outcome was in-hospital mortality. Sociodemographic and clinical variables (heart failure (HF), malnutrition, Charlson Comorbidity Index (CCI), and tumor site) were analyzed using multivariable logistic regression.

RESULTS: Among 5,642 patients (mean age …

Impact Of Tricuspid Regurgitation On The Clinical Outcomes Of Patients With Heart Failure, Muhammad U. Almani, Rasha Khan, Noor Fatima, Muhammad Yousuf, Aman Amanullah

Einstein Health Papers

BACKGROUND: Tricuspid regurgitation (TR) is a common occurrence in patients with heart failure (HF), and its role in disease progression has gained attention in recent years. Although TR can worsen clinical outcomes in HF patients, the impact of gender, racial, and socioeconomic factors remains largely unexplored. With growing evidence supporting the role of percutaneous interventions for the treatment of significant TR, understanding these disparities is more crucial than ever.

METHODS: Data were extracted from the National Inpatient and National Readmission 2016-2020 Databases. We used ICD-10 code I50 to identify the patients primarily admitted for HF and subdivided the cohort into …

Smart Dressings Accelerating Wound Healing With Tranexamic Acid-Infused Aligned Electrospun Nanofibers: In Vitro And In Vivo Assessments, Samar A. Salim, Abdullah Elbadry, Eman Gomaa, Mennatullah Faisal, Elbadawy A. Kamoun

Nanotechnology Research Centre

The development of advanced wound dressings capable of accelerating healing and achieving effective hemostasis remains a critical challenge in managing traumatic and surgical wounds. This study reports the fabrication and comprehensive evaluation of a novel multilayered, sandwich-structured nanofiber scaffold composed of Tranexamic acid (TXA), chitosan (CS), polyvinyl alcohol (PVA), L-arginine, and polylactic acid (PLA) for biodegradable wound dressing applications. Using sequential electrospinning, a four-layered scaffold was developed as a smart wound dressing, comprising an immediate-release TXA-CS-PVA layer for rapid clotting, a hydrophobic PLA barrier layer for protection, a sustained-release L-arginine-PVA layer to promote tissue regeneration, and a final PLA protective …

Effect Of Vitamin D Supplementation During Pregnancy And Lactation On The Development Of Infants Born To Tanzanian Women Living With Hiv: A Secondary Analysis Of A Randomised Controlled Trial, Temiwunmi Shobanke, Alfa Muhihi, Nandita Perumal Phd, Nzovu Ulenga, Fadhlun M. Alwy Al-Beity, Christopher P. Duggan, Wafaie W. Fawzi, Karim P. Manji, Christopher R. Sudfeld

Faculty Publications

Background Infants born to pregnant women living with HIV (WLHIV) are at greater risk for morbidity and mortality and may also have poorer developmental outcomes as compared with infants who are not exposed to HIV. Nutrition interventions in pregnancy may affect developmental outcomes.

Objectives This study evaluated the effect of maternal vitamin D supplementation on infant development outcomes.

Design We conducted a secondary analysis of a randomised, triple-blind, placebo-controlled trial of maternal vitamin D supplementation from June 2015 to October 2019.

Setting Antenatal care clinics in Dar es Salaam, Tanzania.

Participants Pregnant WLHIV and their offspring.

Interventions Daily 3000 IU …

Genome-Wide Association Study Meta-Analysis Uncovers Novel Genetic Variants Associated With Olfactory Dysfunction, Mohammed Aslam Imtiaz, Konstantinos Melas, Adrienne Tin, Valentina Talevi, Honglei Chen, Myriam Fornage, Srishti Shrestha, Martin Gögele, David Emmert, Cristian Pattaro, Peter Pramstaller, Franz Förster, Katrin Horn, Thomas H Mosley, Christian Fuchsberger, Markus Scholz, Monique M B Breteler, N Ahmad Aziz

Faculty, Staff and Student Publications

Background: Olfactory dysfunction is among the earliest signs of many age-related neurodegenerative diseases and has been associated with increased mortality in older adults; however, its genetic basis remains largely unknown. Therefore, here we aimed to elucidate its genetic architecture through a genome-wide association study meta-analysis (GWMA).

Methods: This GWMA included the participants of European ancestry (N = 22,730) enrolled in four different large population-based studies followed by a multi-ancestry GWMA including participants of African ancestry (N = 1,030). Olfactory dysfunction was assessed using a 12-item smell identification test.

Results: GWMA revealed a novel genome-wide significant locus (tagged by single nucleotide …

Evaluating And Optimizing Just-In-Time Adaptive Interventions In A Digital Mental Health Intervention (Wysa For Chronic Pain) For Middle-Aged And Older Adults With Chronic Pain: Protocol For A Series Of Randomized Trials, Abby L Cheng, Joanna Abraham, Sarah M Hartz, Eric B Laber, J Philip Miller

2020-Current year OA Pubs

BACKGROUND: On a population level, digital mental health interventions effectively reduce depression and anxiety symptoms. However, middle-aged and older adults with chronic pain and coexisting depression or anxiety have not been adequately represented in digital mental health studies.

OBJECTIVE: The goal of this study is to refine an existing mobile, digital mental health intervention (Wysa for Chronic Pain) that addresses symptoms of depression, anxiety, and coexisting chronic pain for the unique challenges and technology use patterns of middle-aged and older adults.

METHODS: Using a mixed methods, human-centered design approach and a series of randomized trials, we will test and iteratively …

Bard1: A Friend Or Foe In Pancreatic Ductal Adenocarcinoma?, Lily Zekavat, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid malignancy with poor overall prognosis and limited response to standard treatments. Growing interest in the modulation of DNA repair mechanisms, including the homologous recombination (HR) repair pathway, has opened new avenues for therapeutic development. BARD1 (BRCA1-Associated RING Domain 1) plays a complex role in tumor biology, functioning either as a tumor suppressor or as an oncogenic driver, depending on isoform expression, cellular context, and regulatory environment. In this review, we examine the dual roles of BARD1, focusing on its regulation and paradoxical activities in PDAC. We summarize evidence that BARD1 and BARD1 …