Medical Specialties Commons^™

Netrin-1 Promotes Pancreatic Tumorigenesis And Innervation Through Neo1, Hiroki Kobayashi, Yosuke Ochiai, Junya Arai, Masahiro Hata, Feijing Wu, Masaki Sunagawa, Tadashi Iida, Taisuke Baba, Ermanno Malagola, Takayuki Tanaka, Zhengyu Jiang, Ruth A White, Xiaofei Zhi, Jin Qian, Quin T Waterbury, Ruhong Tu, Biyun Zheng, Yi Zeng, Hualong Zheng, Puran Zhang, Shuang Li, Leah B Zamechek, Jonathan S Labella, Takahiro Sugie, Atsushi Enomoto, Holger K Eltzschig, Carmine F Palermo, Iok In Christine Chio, Kenneth P Olive, Timothy C Wang

Faculty, Staff and Student Publications

Nerves can regulate tumorigenesis and cancer progression. However, clarification of the role of axon guidance molecules in tumorigenesis, innervation, and metastasis is required to better understand the tumor-promoting functions of nerves. Using murine KrasG12D-mutant pancreatic organoids, we screened axon guidance molecules and identified netrin-1 upregulation. Netrin-1 was also upregulated in vivo during pancreatic tumorigenesis in humans and mice. Mutant KRAS and β-adrenergic signaling upregulated netrin-1 and its receptor NEO1 in epithelial cells in part through the MAPK pathway. Ex vivo culture of celiac ganglia showed that netrin-1 promoted the axonogenesis of sympathetic neurons through nerve NEO1. In the Pdx1-Cre;LSL-KrasG12D/+ model, …

Speeding Up Interval Estimation For R2-Based Mediation Effect Of High-Dimensional Mediators Via Cross-Fitting, Zhichao Xu, Chunlin Li, Sunyi Chi, Tianzhong Yang, Peng Wei

Faculty, Staff and Student Publications

Mediation analysis is a useful tool in investigating how molecular phenotypes such as gene expression mediate the effect of exposure on health outcomes. However, commonly used mean-based total mediation effect measures may suffer from cancellation of component-wise mediation effects in opposite directions in the presence of high-dimensional omics mediators. To overcome this limitation, we recently proposed a variance-based R-squared total mediation effect measure that relies on the computationally intensive nonparametric bootstrap for confidence interval estimation. In the work described herein, we formulated a more efficient two-stage, cross-fitted estimation procedure for the R2 measure. To avoid potential bias, we performed …

Association Of Aerobic Performance With Balance, Anaerobic Power, Agility, And Visual Reaction Time In Fencers, Aysel Gökçe Kurt, Manolya Acar

Baltic Journal of Health and Physical Activity

Background: The study aimed to investigate the effects of aerobic performance on balance, anaerobic power, agility, and visual reaction in fencers and was designed as a prospective cohort study. Materials and methods: This study involved 26 fencing athletes (age = 20.35 ± 5.12 years, sports experience: 8.44 ± 4.33 years). The 20-m shuttle test, the vertical jump test, the Y-balance test, the fencing-specific 4-2-2-4 forward-back step method, and the Nelson hand reaction test were used to evaluate aerobic performance, anaerobic performance, balance, agility-change of direction, and visual reaction, respectively. Results: The maximum oxygen consumption determined with a use of the …

Treatment Patterns For Genitourinary Syndrome Of Menopause: A Trinetx Analysis, Anushka Ghosh, Maria D'Amico, Yash B. Shah, Whitney R. Smith, Mihir S. Shah, Costas D. Lallas, Alana M. Murphy

Department of Urology Faculty Papers

BACKGROUND: Genitourinary syndrome of menopause (GSM) is a highly prevalent, underdiagnosed condition that can significantly impair quality of life (QoL). This study evaluates real-world treatment trends for GSM to better understand current management practices and highlight ongoing gaps in care. The background is in a different font than the rest of the abstract.

METHODS: We queried the TriNetX database for patients with a diagnosis of postmenopausal atrophic vaginitis (ICD N95.2) and treatment information from 2004-2024. A combination of RxNorm and International Classification of Diseases-10 (ICD) codes was used to classify disease and treatment type, including topical estrogen (RxNorm 4083, 4099), …

Low Utilization Of Intracavernosal Injection And Penile Doppler Ultrasound In The Evaluation Of Erectile Dysfunction And Peyronie's Disease, Joon Yau Leong, Tyler Gaines, Zachary J. Prebay, David Ebbott, Paul H. Chung

Department of Urology Faculty Papers

INTRODUCTION: Despite the diagnostic value of intracavernosal injections (ICI) and penile Doppler ultrasound (PDUS), there remain barriers to widespread clinical adaptation of these methods. The study aimed to evaluate the practice patterns of utilization of ICI and PDUS in the assessment of erectile dysfunction (ED) and Peyronie's disease (PD).

METHODS: Using the TriNetX database (Cambridge, MA, USA), adult (≥18 years) male patients with a diagnosis of ED on oral phosphodiesterase-5 (PDE5) inhibitors were identified. Current Procedural Terminology codes were utilized to identify patients who underwent further evaluation with ICI or PDUS, as well as penile prosthesis placement after PDUS. A …

A Rare Culprit Or An Elusive Culprit In Disguise? Unraveling Wild-Type Attr Cardiac Amyloidosis In Heart Failure With Reduced Ejection Fraction, Jose J. Loayza Pintado, Taiwo Ajani, Daniela Hernandez, Everardo Cobos

School of Medicine Publications

Cardiac amyloidosis (CA) is a rare disorder caused by the deposition of abnormal proteins called amyloid in the myocardium, leading to dysfunction. The 2 most common forms of amyloidosis are AL (light chain) and ATTR (transthyretin). Diagnosing amyloidosis is challenging, especially in its early stages, due to its nonspecific symptoms and overlap with other conditions. Recent studies suggest that the incidence of wild-type transthyretin amyloidosis is rising, likely due to improved diagnostic techniques and an aging population. We present the case of a 72-year-old male with lower extremity edema, progressive shortness of breath, and worsening renal function. He had a …

Psoriasis Treatments In The Stabilization Of Atherosclerosis: A Systematic Review, Lixin Ji, Sowmya Ravi, Laura Wright, Vi Nguyen, Jose Wiley, Milena Vukelic, Sangkyu Kim

School of Medicine Faculty Publications

This systematic review explores the relationship between achieving minimal disease activity in psoriasis and the progression of atherosclerosis. It investigates how biologic therapies and other treatments impact atherosclerosis markers, offering insights into therapeutic strategies. A comprehensive search of PubMed, Embase, and Web of Science was conducted from January 1, 2000, to April 1, 2023, using terms such as psoriasis, psoriatic arthritis, atherosclerosis, biologic therapy, vascular stiffness, carotid intima-media thickness (CIMT), and coronary computed tomography angiography (CCTA). Eligible studies were those involving human subjects over 18, written in English, that provided quantitative atherosclerosis markers, including CIMT, CCTA, arterial pulse wave velocity …

Mutational Analysis Of Human Norovirus Vp2 Elucidates Critical Molecular Interactions For Virus Assembly, Janam J Dave, Sue E Crawford, Robert L Atmar, Khalil Ettayebi, B V Venkataram Prasad, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are the leading cause of viral gastroenteritis, with ≥80% of infections caused by the GII genogroup. HuNoVs are non-enveloped, with an icosahedral capsid composed of 90 dimers of the major capsid protein VP1, which encloses a minor structural protein, VP2, and a VPg-linked, positive-sense ssRNA genome. Although the atomic structure of the icosahedral capsid formed by VP1 is well characterized using crystallography and cryo-electron microscopy analyses of HuNoV virus-like particles, the structures and the localization of VP2 and VPg inside the capsid, how they are incorporated into the capsid, and whether this process requires interactions between them …

Documenting Death: Maternal Mortality And The Ethics Of Care In Tanzania (Adrienne E. Strong 2020), Luluk Oktavia, Megawati Sukarno

Paradigma: Jurnal Kajian Budaya

In recent decades, global efforts to reduce maternal mortality have become a primary focus in health development agendas. However, challenges in providing quality healthcare remain complex, especially in resource-limited countries. Adrienne E. Strong’s book, Documenting Death: Maternal Mortality and the Ethics of Care in Tanzania, offers an ethnographic perspective on the relationship between bureaucratic structures, resource constraints, and healthcare practices in Tanzania. This review examines Strong’s key concepts, such as good enough care, documented care, and fierce care, which highlight the ethical dilemmas faced by healthcare workers in delivering care under administrative pressures and limited facilities. The critique of the …

Efficacy And Safety Of Transcatheter Mitral Valve Repair (Mitraclip) Compared To Medical Therapy And Surgery In Patients With Secondary Mitral Regurgitation: A Systematic Review & Pairwise Meta-Analysis, Salma Younas, Aditya Rana, Mirza Faizan Ali Beig, Sweta Sahu, Cynthia Esohe Emanemua, Aisha Ashiq Reshie, Lamees Kaukab, Dileep Duggineni, S K S S P Ashish Gokavarapu, Padamati Bhavani, Afrasayab Khan, Peter G. Fattal

Journal of the Saudi Heart Association

Background: Secondary mitral regurgitation (SMR) is a frequent complication of heart failure, associated with high morbidity and mortality. While surgery is the standard for primary MR, many SMR patients are poor surgical candidates. Transcatheter mitral valve repair (TMVr) using the MitraClip offers a less invasive alternative, but its comparative efficacy and safety remain under active investigation and controversial. Methods: A systematic search of MEDLINE®, Embase®, and the Cochrane Library was conducted per PRISMA guidelines (PROSPERO ID: CRD420251016943). Eligible studies were randomized controlled trials (RCTs) comparing TMVr (MitraClip) with guideline-directed medical therapy (GDMT) or surgical repair in adult patients with SMR. …

Subgroup Analyses Of The Phase 3 Focus Study Of Melphalan/Hepatic Delivery System In Patients With Unresectable Metastatic Uveal Melanoma, Jonathan S. Zager, Marlana Orloff, Pier Francesco Ferrucci, Junsung Choi, David J. Eschelman, Evan S. Glazer, Aslam Ejaz, Erika Richtig, Sebastian Ochsenreither, Sunil A. Reddy, Michael C. Lowe, Georgia M. Beasley, Anja Gesierich, Martin Gschnell, Reinhard Dummer, Ana Arance, Stephen William Fenwick, Joseph J. Sacco, Johnny John, Matthew Wheater, Christian H. Ottensmeier

Department of Medical Oncology Faculty Papers

PURPOSE: To assess efficacy and safety in subgroups of patients treated with Melphalan/Hepatic Delivery System (melphalan/HDS), a drug/device combination for liver-directed treatment of metastatic UM (mUM) patients. Previously reported FOCUS study results indicated melphalan/HDS treatment provides a clinically meaningful response rate and favorable benefit-risk ratio in patients with unresectable mUM.

METHODS: Patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) every 6-8 weeks for up to 6 cycles. Post hoc analyses of efficacy and safety were conducted for patient subgroups based on demographic and baseline disease characteristics.

RESULTS: 102 patients with mUM were enrolled; treatment was attempted …

Concentric Macular Rings And Oct Corrugations In Foveal Hypoplasia: Proof Of Concept For An Optical Interference Mechanism, Ari August, Ralph Eagle, Tatyana Milman, Rebecca Procopio, Bruce Schnall, Jose Pulido

Wills Eye Hospital Papers

BACKGROUND: Concentric macular rings (CMR) and Henle fiber layer (HFL) corrugations, potential clinical biomarkers of foveal hypoplasia, have been observed in laser fundus photographs and optical coherence tomography (OCT) images, respectively. Some believe these findings represent true anatomical structural changes while others hypothesize that they are artifacts of interference; however, to our knowledge, no previous study has provided evidence to support either theory.

METHODS: This retrospective case series analyzed CMR and OCT corrugations in 3 patients (6 eyes) with foveal hypoplasia. Dark fringe diameters of CMR at different wavelengths (λ: red = 635, green = 532, blue = 488 nm) …

Perspectives On Implementing Environmentally Sustainable Practices In Cataract Surgeries: Interviews Of Administrative And Frontline Healthcare Workers, Daniel Parra, Brooke Sherry, Emma Pak, Lauren Taylor, Erin S. Rogers, Sarah E. Hochman, Maria De Los Angeles Ramos Cadena, Joel S. Schuman, Christina R. Prescott, Cassandra L. Thiel

Wills Eye Hospital Papers

BACKGROUND: Healthcare is responsible for 8.5% of greenhouse gas emission in the United States. Physicians are becoming increasingly concerned about the climate crisis, particularly in the field of ophthalmology where there is a growing body of literature related to sustainability. Although emissions of cataracts surgery, one of the most performed surgical procedures in the world, have been quantified, modifications to practice have yet to be made. This study aims to uplift the perspectives of a diverse set of healthcare workers on implementing environmentally sustainable practices in the cataract surgery setting.

METHODS: 16 semi-structured interviews were conducted with professionals working in …

Non-Invasive Diagnosis Of Pulmonary Tuberculosis Using Face Mask Sampling: A Prospective Study In Adults, Dariusz Woelk, Lennard Meiwes, Nelly Ciobanu, Valeriu Crudu, Anna-Marya Comanac, Stela Kulcitkaia, Anca Vasiliu, Anna Maria Mandalakas, Christoph Lange, Thomas Theo Brehm, Dumitru Chesov

Faculty, Staff and Students Publications

Objectives: Sputum-based diagnostic methods for pulmonary tuberculosis (TB), including culture and nucleic acid amplification tests, provide high sensitivity and specificity. However, these methods rely on the patients' ability to produce sputum. In cases where sputum cannot be obtained, invasive procedures like bronchoscopy may become necessary. Our objective was to evaluate the diagnostic accuracy of face mask sampling (FMS) as a non-invasive alternative.

Methods: Adults with microbiologically confirmed pulmonary TB who had received fewer than three days of anti-TB therapy were recruited in Chişinău, Moldova. FMS was conducted and samples were analyzed on-site using Xpert MTB/RIF Ultra. Diagnostic performance was compared …

Black Bone Mri Morphometry For Mandibular Cortical Bone Measurement In Head And Neck Cancer Patients: Prospective Method Comparison With Ct, Lisanne V Van Dijk, Juan Ventura, Kareem A Wahid, Lin L Zhu, Brigid A Mcdonald, Sara Ahmed, Keith L Sanders, Sonja M Stieb, Lance Mccoy, Christina S Sharafi, Kathryn E Preston, Natalie A West, Sarah Mirbahaeddin, Dina M El-Habashy, Travis Salzillo, Samuel Mulder, Joly Fahim, Aubryane Dearmas, Mona Arbab, Yao Ding, Jihong Wang, Bastien Rigaud, Anando Sen, Mark Chambers, Katherine A Hutcheson, Kristy K Brock, Abdallah S R Mohamed, Stephen Y Lai, Clifton D Fuller

Faculty, Staff and Student Publications

Objectives: Determine the utility of low-flip angle "black bone" magnetic resonance imaging (MRI) for cortical mandibular bone assessment compared to computed tomography (CT).

Methods: Quantification of cortical mandibular bone width was performed per Hamada et al. at 15 cross-sectional interdentium locations on pretreatment black bone MRI and CT for 15 oropharyngeal cancer patients, with interobserver analyses on a subset of three patients by 11 observers. CT and MRI measurements were compared using Bland-Altman analysis, Lin's concordance, and Deming regression; interobserver variability was assessed with absolute variance and intraclass correlation coefficient (ICC).

Results: Bland Altman and Deming regression analyses showed CT …

Sex Differences In Bile Acid Homeostasis And Excretion Underlie The Disparity In Liver Cancer Incidence Between Males And Females, Megan E Patton, Sherwin Kelekar, Lauren J Taylor, Angela E Dean, Qianying Zuo, Rhishikesh N Thakare, Sung Hwan Lee, Emily C Gentry, Morgan Panitchpakdi, Pieter Dorrestein, Yazen Alnouti, Zeynep Madak-Erdogan, Ju-Seog Lee, Milton J Finegold, Sayeepriyadarshini Anakk

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC), the common liver cancer, exhibits higher incidence in males. Here, we report that mice lacking bile acid (BA) regulators, Farnesoid X Receptor (FXR also termed NR1H4) and Small Heterodimer Partner (SHP also termed NR0B2), recapitulate the sex difference in liver cancer risk. Since few therapeutic options are available, we focused on understanding the intrinsic protection afforded to female livers. Transcriptomic analysis in control and NR1H4 and NR0B2 double knockout livers identified female-specific changes in metabolism, including amino acids, lipids, and steroids. To assess translational relevance, we examined if transcriptomic signatures obtained from this murine HCC model correlate …

Batf2 Is A Glutamine-Responsive Tumour Suppressor Required For Type-I Interferon-Dependent Anti-Tumour Immunity, Wang Gong, Hülya F Taner, Yuesong Wu, Yumin He, Xingwu Zhou, Zaiye Li, Xin Hu, Charisse Ursin, Kala Chand Debnath, Kohei Okuyama, Qiang Hu, Christopher R Donnelly, Felipe Nör, Chamila D Perera, Emily Bellile, Arash Yunesi, Zhiqian Zhai, Mei Zhao, Wanqing Cheng, Zackary R Fitzsimonds, Luke Broses, Jiaqian Li, Shadmehr Demehri, Deepak Nagrath, Gregory T Wolf, Andrew G Sikora, Yanbao Yu, Haitao Wen, Lei Wei, Steven B Chinn, Jeffrey N Myers, Shizuo Akira, Yuying Xie, James J Moon, Yu Leo Lei

Faculty, Staff and Student Publications

Recent evidence highlights the significance of a new type of tumour suppressors, which are not frequently mutated but inhibited by metabolic cues in cancers. Here, we identify BATF2 as a tumour suppressor whose expression is epigenetically silenced by glutamine in Head and Neck Squamous Cell Carcinomas (HNSCC). BATF2 correlates with type-I interferon and Th1 signatures in human HNSCC, with correlation coefficients even stronger than those of the positive control, STING. The phosphorylation of BATF2 at serine 227 promotes the oligomerization of STING. BATF2 deficiency or high glutamine levels result in higher oxygen consumption rates and metabolic profiles unfavorable for …

A Pouch Of Trouble For The Pancreas: Unmasking A Case Of Lemmel Syndrome, Aravindharaj Tamilselvan, Sabari Ramesh

Manipal Journal of Medical Sciences

Lemmel syndrome is a rare cause of biliary and pancreatic obstruction arising from periampullary duodenal diverticula. We report a 72-year-old woman presenting with acute pancreatitis, biliary dilation, and a periampullary diverticulum causing distal CBD compression. Multimodality imaging, including CT and MRCP, established the diagnosis. Although ERCP was advised, the patient declined and improved with conservative management. Early recognition of this uncommon entity is essential to prevent recurrent pancreatobiliary complications.

Role Of Gut Microbiome In Oncogenesis And Oncotherapies, Renuka Sri Sai Peddireddi, Sai Kiran Kuchana, Rohith Kode, Saketh Khammammettu, Aishwarya Koppanatham, Supriya Mattigiri, Harshavardhan Gobburi, Suresh K. Alahari

School of Graduate Studies Faculty Publications

The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing …

Metabolic Syndrome As A Risk Factor For Postoperative Complication In Patients Undergoing Spine Surgery: A Systematic Review And Meta-Analysis Of More Than 3 Million Cases, Amir-Mohammad Asgari, Farhad Shaker, Mohammad Taha Pahlevan Fallahy, Sourena Sharifkashani, Alireza Soltani Khaboushan, Dorsa Salabat, César Carballo Cuello, James Harrop, Puya Alikhani

Department of Neurosurgery Faculty Papers

OBJECTIVE: Including conditions like obesity, diabetes, hypertension, and dyslipidemia, metabolic syndrome disrupts metabolic homeostasis and impairs recovery, increasing the risk of surgical complications. This study evaluates the impact of metabolic syndrome on spine surgery outcomes, addressing inconsistencies in the existing literature.

METHODS: Four databases were searched until December 2024 for studies comparing the postoperative complication rates of spine surgeries between patients with and without metabolic syndrome. Following deduplication, 2 authors independently reviewed the studies. For each included study, demographics and incidence rates of postoperative complications were extracted separately by 2 authors. Data analysis was performed using R.

RESULTS: After deduplication, …

Synergizing Digital And Print: Leveraging Spine Surgeons' Social Media To Transform Publishing And Society Interaction, Benedikt W. Burkhardt, Kai-Uwe Lewandrowski, Choll W. Kim, Morgan P Lorio, Oscar L. Alves, Rossano Kepler Alvim Fiorelli, Sergio Luis Schmidt, Hansen A. Yuan, Alex R. Vaccaro

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Social media has fundamentally altered how information is created, disseminated, and consumed, with growing impact on spine surgeons and professional societies. Traditional academic publishing remains the standard for research validation, but digital platforms now shape much of the real-time dialogue in spine care.

OBJECTIVE: To explore strategies for integrating spine surgeons' social media presence with traditional publishing channels to enhance knowledge dissemination, support clinical innovation, and improve member engagement within spine societies.

METHODS: This perspective reviews current patterns of social media use among spine surgeons, focusing on platforms such as X (formerly Twitter), Instagram, and LinkedIn. It analyzes benefits …

Regenerative And Wellness Medicine: A Boon Or Barrier To Surgical Innovation In Degenerative Spine Care?, Álvaro Dowling, Kai-Uwe Lewandrowski, Morgan P. Lorio, Óscar L. Alves, Rossano Kepler Alvim Fiorelli, Sergio Luis Schmidt, Hansen A. Yuan, Alexander R. Vaccaro

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Regenerative and wellness medicine is rapidly reshaping health care, particularly in the management of degenerative spine conditions. Noninvasive or minimally invasive options such as stem cell therapy, platelet-rich plasma (PRP) injections, and holistic wellness programs are increasingly selected by patients who wish to avoid the risks, costs, and prolonged recovery associated with elective spine surgery.

PURPOSE: This perspective article examines whether regenerative and wellness approaches function primarily as a boon or a barrier to innovation in spine surgery and explores their impact on traditional, insurance-based surgical care models.

METHODS: Using a narrative, opinion-based framework, this article synthesizes current trends …

A Spatiotemporal Model Of Cxcl10 As A Master Regulator Of Immune Evasion And Metastasis In Osteosarcoma, Benjamin B Gyau, Tsz-Kwong Man

Faculty, Staff and Students Publications

The C-X-C motif chemokine ligand 10 (CXCL10) is implicated in the progression of osteosarcoma (OS), the most aggressive pediatric bone malignancy. However, its role often presents a profound clinical paradox: although high circulating levels are strongly linked to poor prognosis, its canonical function is to recruit anti-tumor immune cells. This review unravels these contrasting roles by proposing a novel spatiotemporal model. We argue that in the early stages, immune-evading OS cells initiate the formation of a pre-metastatic niche (PMN) in the lungs, creating a localized inflammatory environment that becomes the primary source of elevated circulating CXCL10. As the disease progresses, …

Amino Acid Signaling In Skeletal Muscle Is Blunted By Prematurity In A Piglet Model, Antonio C Ramos Dos Santos, Agus Suryawan, Ki Beom Jang, Rosemarie D Parada, Mahmoud A Mohammad, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

Background: Preterm (PT) infants are at increased risk for reduced postnatal lean mass accretion. We established that the feeding-induced stimulation of protein synthesis in skeletal muscle is blunted in piglets born PT compared with those born at term.

Objectives: We evaluated the extent to which key components of the amino acid-sensing pathways that regulate mechanistic target of rapamycin complex 1 (mTORC1) activation contribute to anabolic resistance in skeletal muscle of piglets born PT compared with those born term.

Methods: Piglets delivered by cesarean section 10 d PT (n = 23) or at term (n = 22) were administered total parenteral …

Collagen Type Ii-Targeting Lentiviral Gene Therapy For Mucopolysaccharidosis Iva, Betul Celik, Sampurna Saikia, Shaukat Khan, Krishna Sai Musini, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis (MPS IVA) is caused by pathogenic variations in the GALNS gene, leading to the accumulation of glycosaminoglycans in tissues and causing progressive skeletal lesions. While conventional lentiviral vectors (LVs) provide long-term stable expression, they do not deliver therapeutic levels to bone and cartilage. We hypothesized that engineering the LV envelope with a collagen type II-targeting peptide (WYRGRL) increases the binding affinity of the LVs for bone and cartilage. These modified vectors carrying the CBh and COL2A1 promoters delivered the GALNS gene to MPS IVA newborn mice via intravenous (IV) or intraarticular (IA) administration. The peptide-modified LVs exhibited markedly increased …

Loss Of The Maternal Effect Gene Nlrp2 Impairs Embryonic And Extra-Embryonic Development, Revealing A Novel Genetic Cause Of Congenital Anomalies†, Momal Sharif, Zahra Anvar, Imen Chakchouk, Sara H El-Dessouky, Roni Zemet, Eric C Kao, Wessam E Sharaf-Eldin, Ying-Wooi Wan, Zhandong Liu, Pengfei Liu, Michael Jochum, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

Maternal-effect genes (MEGs) play a crucial role in early mammalian development, and their dysfunction can lead to severe embryonic and extra-embryonic abnormalities. NLRP2, a MEG that encodes a subcortical maternal complex (SCMC) protein, has been implicated in preimplantation development, but its role after implantation remains underexplored. In this study, we investigated the developmental consequences of maternal Nlrp2 loss-of-function in a maternal knockout (KO) mouse model at embryonic day 11.5. Embryos derived from Nlrp2-KO females have abnormal yolk sac vasculature, increased embryonic resorption, craniofacial abnormalities, neural tube defects, and congenital heart defects. Placental architecture is disrupted with an altered junctional zone …

Tumor Biology And Access To Care And Metastatic Breast Cancer Outcomes, Matthew R. Dunn, Sarah C. Van Alsten, Marc A. Emerson, Katherine Reeder-Hayes, Terry Hyslop, Melissa A. Troester

Kimmel Cancer Center Faculty Papers

PURPOSE: To understand how access to care influences metastatic breast cancer burden (MBC) while accounting for molecular tumor characteristics, and identify interventions to reduce metastatic disease burden.

METHODS: The Carolina Breast Cancer Study is a population-based cohort with invasive breast cancer (diagnosed 2008-2013). Both de novo metastasis (stage IV at diagnosis) and distant recurrence were evaluated (12 years of follow-up. Tumor data were from medical records, pathology reports, and RNA expression data. Social variables and access to care were from participant surveys. Generalized linear models were used to estimate associations of biological and access characteristics with MBC; Cox models were …

Managing The Uncertainty Of "Precision" While Navigating Goals Of Care: A Framework For Collaborative Interpretation Of Complex Genomic Testing Results In Critically-Ill Neonates, Donnamaria E. Cortezzo, Katharine Press Callahan, Bimal P. Chaudhari, Elliott M. Weiss, Monica Hsiung Wojcik, Krishna Acharya, Amy B. Schlegel, Kevin M. Sullivan, Jessica T. Fry

Department of Pediatrics Faculty Papers

Each year, many neonates are born with genetic diagnoses that carry a range of prognoses. As the types and availability of genetic testing have expanded, neonatal intensive care units (NICUs) have served as "launching points" for their clinical application. Broad genetic testing has both improved diagnostic precision and expanded uncertainty. Genetic information may be explicitly uncertain, as in the case of a variant of unknown significance (VUS). But it is also frequently uncertain whether/how the information relates to a patient's phenotype or what it may mean for a child's future. Even without ambiguity in the diagnosis or prognosis, the significance …

Sex Differences In The Association Of Vascular Risk And Apoe Genotype With Cognitive Decline And Dementia: Evidence From A U.S. Longitudinal Study, Longjian Liu, Jintong Hou, Saishi Cui, Xiaopeng Zhao, Zuolu Liu, J. Craig Longenecker, Nathalie S May, Jin Jun Luo, Rose Ann Dimaria-Ghalili, Howard J. Eisen

Division of Cardiology Faculty Papers

BACKGROUND: Sex differences in the association between vascular factors and cognitive outcomes remain unclear. We aimed to investigate the associations of blood pressure metrics (hypertension, systolic blood pressure [SBP), pulse pressure, ankle and brachial pressures, and ankle to brachial pressure index [ABI]) with the risk of cognitive decline and dementia.

METHODS: We conducted a population-based longitudinal analysis using data from the Atherosclerosis Risk in Communities (ARIC) study (begun in 1987-1989) in the United States. We analyzed a total of 12,268 participants aged 45-64 years who had validated exposure measurements, cognitive function tests (first administrated 1990-1992), and followed up for incidence …

The Impact Of Targeting Traf2 And Nck-Interacting Protein Kinase On Antitumor Effect And Tumor Immune Environment In C-Myc-High Sclc, Azusa Tanimoto, Kavya Ramkumar, C Allison Stewart, Bingnan Zhang, Kyle Concannon, Robert J Cardnell, Li Shen, Qi Wang, Jing Wang, Carl M Gay, Lauren Averett Byers

Faculty, Staff and Student Publications

Introduction: Wnt/β-catenin signaling pathway activation contributes to tumorigenesis and chemo-resistance in SCLC, yet clinical attempts to target this pathway have been unsuccessful. TRAF2 and NCK-interacting protein kinase (TNIK), an essential nuclear activator of Wnt/β-catenin target genes, has not yet been validated as a viable therapeutic target in SCLC. Here, we validated that TNIK inhibition is a promising approach for personalized anticancer therapy in SCLC.

Methods: We correlated the IC50 values of a TNIK inhibitor, NCB-0846, with proteomic profiling (reverse phase protein array) data across 28 SCLC cell lines. Cytokine array analysis was performed to quantify changes in 105 cytokines after …