Digital Commons Network^™

Chemoradiation After Chemotherapy For Metastatic Cervical Cancer Can Provide Chemo-Free Time, Spoorthi Kamepalli, Ashley Chavana, Michelle Ludwig, Madeline Flanagan, Shelly Sharma, Tracilyn Hall, Anthony Costales, Jan Sunde, Claire Hoppenot

Faculty, Staff and Students Publications

Introduction: Stage IVB cervical cancer is treated with a life-prolonging and palliative intent with systemic chemotherapy and immunotherapy. The purpose of this study was to evaluate the number of these patients who had an adequate response to chemotherapy to be eligible for consolidative radiosensitizing chemotherapy and radiation (chemoradiation) and subsequent outcomes.

Materials and methods: This is a retrospective review of metastatic cervical cancer patients treated with chemotherapy and evaluated for treatment with consolidative pelvic chemoradiation at a single safety-net hospital system from 2016 to 2024. Demographic data and clinical information were collected from electronic medical records. Stata was used for …

Phase I Study Of Niraparib With Radiotherapy For Treatment Of Metastatic And Locally Advanced Invasive Carcinoma Of The Cervix (Nivix), Piyush Pathak, Eunji Jo, Susan Hilsenbeck, Matthew L Anderson, Alfredo Echeverria, Shelly Sharma, Jan Sunde, Tracilyn Hall, Anthony Costales, Claire Hoppenot, Michelle Ludwig

Faculty, Staff and Students Publications

Introduction: This Phase I study evaluated the safety and tolerability of concurrent niraparib, an oral poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, with definitive radiotherapy in women with locally advanced or platinum-sensitive metastatic cervical cancer. Dose escalation followed a Bayesian Optimal Interval (BOIN) design with a target dose-limiting toxicity (DLT) rate of 30%.

Methods: Women ≥18 years with FIGO stage IIIC2 (bulky nodes >1 cm) or stage IV cervical cancer demonstrating response to platinum-based induction chemotherapy were eligible. Niraparib 100 mg was administered daily concurrent with pelvic radiotherapy (45-57.5 Gy via IMRT with nodal boosts) and brachytherapy, continuing 28 days post-radiation. Per …

Phase 1 Trial Of Withania Somnifera Leaf Extract (Rh324) In Advanced Non-Small Cell Lung Cancer Including [18f]Fdg Pet/Ct As A Short-Term Metabolic Biomarker To Assess Efficacy: A Novel Model For Assessment Of Complimentary Therapies In Early Phase Human Clinical Trials, Jin Uk Heo, Santosh Rao, Herbert B Newton, Afshin Dowlati, Raymond F Muzic, Arash Kardan

Faculty, Staff and Students Publications

Background: Withania somnifera (WS), commonly known as ashwagandha, has been used in the traditional medical system of India. It has shown significant activity against numerous solid tumor varieties in pre-clinical in vitro and in vivo studies. This study focuses on RH324 (ReHeva Biosciences, Columbus, OH), a pharmaceutical-grade formulation derived from WS, which has received FDA allowance for clinical development as a botanical drug in the treatment of cancer.

Methods: A phase 1 open label dose ranging study of oral RH324 in advanced non-small cell lung cancer (NSCLC) was conducted. The primary endpoint of the study was assessment of short-term safety …

Immune-Mediated Diarrhea And Colitis With Normal Biochemical, Endoscopic And Histologic Findings: A Retrospective Study, Malek Shatila, Sharada Wali, Carolina Colli Cruz, Kei Takigawa, Andres Caleb Urias Rivera, Kian Abdul-Baki, Tanvi Gupta, Elliot Baerman, Linfeng Lu, Irene Jeong-Ah Lee, Raakhi Menon, Hamza Salim, Andrew Sullivan, Varun Vemulapalli, Cristina Natha, Ayesha Khan, Krishnavathana Varatharajalu, Stephane Champiat, Kerry L Reynolds, Lucy B Kennedy, Katy Tsai, Anusha Shirwaiker Thomas, Yinghong Wang

Faculty, Staff and Students Publications

Background: Immune-mediated diarrhea and colitis (IMDC) due to checkpoint inhibition infrequently presents with normal stool biomarkers and no endoscopic or histologic evidence of inflammation. Little is known about the treatment needs and outcomes of this subset of patients. We aimed to describe this entity and clarify the role of immunosuppressive treatments in its management.

Method: This was a single-center, retrospective study of patients treated with immune checkpoint inhibitors who developed clinical symptoms of IMDC, with no evidence of inflammation based on fecal calprotectin or endoscopic/histologic evaluation, between January 2010 and February 2024.

Results: Of 1151 patients with IMDC, 131 (11.4%) …

Interdisciplinary Swiss Consensus Recommendations For Follow-Up After Radical Cystectomy And Trimodal Treatment For Muscle-Invasive Bladder Cancer, Ernest Kaufmann, Stefanie Aeppli, Andres Affentranger, Nicolas Arnold, Winfried Arnold, Fabian Aschwanden, Panagiotis Balermpas, Jörg Beyer, Uwe Bieri, Joost Boormanns, Richard Cathomas, Berardino De Bari, Marco Dressler, Daniel S Engeler, Andreas Erdmann, Andrea Gallina, Silvia Gomez, Matthias Guckenberger, Thomas Herrmann, Thomas Hermanns, Ilaria Lucca, Hubert John, Thomas Matthias Kessler, Jan Klein, Mohamed Laouiti, David Lauffer, Seth Paul Lerner, Agostino Mattei, Michael Müntener, Daniel Nguyen, Philipp Niederberger, Alexandros Papachristofilou, Lukas Prause, Paul Martin Putora, Karsten Reinhardt, Emanuela Salati, Philippe Sèbe, Mohamed Shelan, Silvan Sigg, Räto Thomas Strebel, Arnoud Jan Templeton, Ursula Vogl, Marian Severin Wettstein, Stephen Wyler, Deborah Zihler, Thomas Zilli, Daniel Zwahlen, Beat Roth, Christian Daniel Fankhauser

Faculty, Staff and Students Publications

Introduction: Radical cystectomy or trimodal therapy are treatment options for non-metastatic bladder cancer. However, there is limited evidence guiding post-treatment follow-up regimens, resulting in variations in care.

Objective: A Swiss consensus meeting aimed to identify gaps in follow-up strategies and subsequently tailoring follow-up protocols after curative treatment for bladder cancer.

Methods: A consensus meeting including participants from urology, oncology, radiation oncology, neuro-urology, international advisors, and patient representatives was held. 19 pre-formulated questions addressing follow-up duration, frequency, and modalities after radical cystectomy or trimodal therapy for bladder cancer were discussed and voted by participants.

Results: 42 experts from 22 institutions participated …

The All Of Us Evenings With Genetics Research Program, Stacy M Lloyd, Jasmine Baker, Carolina Jorgez, Julie Coleman, Laterrica Williams, April Adams, Ashley Butler, Elizabeth Atkinson, Shamika Ketkar, Steven Scherer, Kim Worley, Susan Fernbach, Keasia Daniels, Latanya Hammonds-Odie, Laura Rosales, Brendan Lee, Debra Murray

Faculty, Staff and Students Publications

The All of Us Evenings with Genetics (All of Us EwG) Research Program, funded in part by the National Institute of Health’s All of Us Research Program, engages researchers to utilize the All of Us Researcher Workbench to advance precision medicine. The All of Us EwG program has two core aims: (1) address barriers to research productivity for minorities, disadvantaged, and persons with disabilities aspiring to enter STEM fields; and (2) promote the use of the All of Us Researcher Workbench to develop research focused on health equity. To achieve these goals, the program implements three key activities: (1) …

Neurotensin Drives Theca Cell Migration During Ovulation In Primates, Jessica S. Miller, Megan A. G. Sage, Thomas E. Curry Jr., Diane M. Duffy

Department of Biomedical and Translational Sciences Faculty Publications

Theca cells are a critical steroidogenic cell type of the ovarian follicle and corpus luteum. The ovulatory luteinizing hormone (LH) surge (or human chorionic gonadotropin (hCG)) stimulates theca cell relocation from the stroma surrounding the dominant follicle to full integration into the developing corpus luteum. Luteinizing hormone/human chorionic gonadotropin also stimulates granulosa cells to produce local mediators of ovulation, including the peptide neurotensin (NTS). To determine if hCG-stimulated NTS regulates theca cell relocation within the ovulatory follicle, vehicle or an NTS receptor antagonist was injected into a macaque dominant follicle, and ovaries were removed 48 h after hCG administration. Additional …

Skeletal Muscle Myofiber Development In Non-Human Primate Offspring Deprived Of Estrogen In Utero, Phillip J. Gauronskas, Terrie J. Lynch, Eugene D. Albrecht, Gerald J. Pepe

Department of Biomedical and Translational Sciences Faculty Publications

Introduction: We previously showed that baboon offspring born to mothers deprived of estrogen during the second half of gestation exhibited insulin resistance prior to and after the onset of puberty. Moreover, the size of skeletal muscle myofibers and the number of microvessels important for delivery of insulin/glucose to myofibers were lower in near-term fetuses deprived of estrogen during pregnancy, and myofiber capillarization remained reduced in post-pubertal offspring deprived of estrogen in utero. However, it remains to be determined whether skeletal muscle size is restored to normal in animals deprived of estrogen in utero after the onset of puberty/gonadal estrogen production. …

Brief Pulses Of High-Level Fluid Shear Stress Enhance Metastatic Potential And Rapidly Alter The Metabolism Of Cancer Cells, Amanda N. Pope, Devon L. Moose, Guy O. Hudson, Hank R. Weresh, Marion R. Dykstra, Aabha Y. Joshi, Patrick Breheny, Eric B. Taylor, Michael D. Henry

Department of Biomedical and Translational Sciences Faculty Publications

Circulating tumor cells (CTCs) face challenges to their survival, including mechanical and oxidative stresses that are different from cancer cells in solid primary and metastatic tumors. The impact of adaptations to the fluid microenvironment of the circulation on the outcome of the metastatic cascade is not well understood. Here, we find that cancer cells exposed to brief pulses of high-level fluid shear stress (FSS) exhibit enhanced invasiveness and anchorage-independent proliferation in vitro and enhanced metastatic colonization/tumor formation in vivo. Cancer cells exposed to FSS rapidly alter their metabolism in a manner that promotes survival by providing energy for cytoskeletal remodeling …

Stat4-Dependent Regulation Of Neuroinflammation In Atherosclerosis, Natalie Stahr, Alina K. Moriarty, Shelby D. Ma, W. Coles Keeter, Woong-Ki Kim, Larry D. Sanford, Elena V. Galkina

Department of Biomedical and Translational Sciences Faculty Publications

Atherosclerosis is linked to an increased risk of cognitive decline, with chronic inflammation being a common feature of both pathologies. IL-12 activates STAT4 to regulate myeloid cell functions, and blockade of this pathway alleviates cognitive impairment in Alzheimer's models. However, the mechanisms connecting vascular pathology to neuroinflammation remain unclear. Here, we examine whether STAT4 functions as a common mediator of neuroinflammation in atherosclerosis. We demonstrate that LysM^Cre-specific STAT4 deficiency ameliorates deficits in long-term memory in low-density lipoprotein-deficient (Ldlr^-/-) mice fed a high-fat diet (HFD-C). STAT4 deficiency moderately reduces Ser199-phosphorylated Tau burden. Atherosclerosis alters brain immune …

Estrogen Deprivation During Primate (Papio Anubis) Pregnancy: Impact On Systemic Microvascular Flow And Cardiovascular Development And Function After Birth In Offspring, Sifa Turan, Jeffery S. Babischkin, Graham W. Aberdeen, Gerald J. Pepe, Eugene D. Albrecht

Department of Biomedical and Translational Sciences Faculty Publications

Background

Suppressing estradiol (E₂) during baboon pregnancy lowers offspring skeletal muscle capillary density, vital for insulin-mediated glucose uptake, and induces insulin resistance. We examined whether E₂ deprivation also impairs microvascular flow and cardiac function.

Methods

Offspring of untreated baboons, letrozole-treated baboons, or letrozole plus E₂ (maternal s.c. injections during the second half of gestation) underwent contrast-enhanced microbubble ultrasonography to quantify microvessel flow and echocardiography to assess cardiac performance.

Results

Letrozole reduced maternal serum E₂ by 95% (p <  0.01). In letrozole offspring, microbubble flux rate (β) fell 55% (p <  0.02), replenishment was 5 s slower (p <  0.03), and microvessel flow declined 40% (p = 0.05); all were restored by added E₂. Indices of systolic (isovolumic contraction), diastolic (isovolumic relaxation), global performance (Tei index), and cardiac output were unchanged.

Conclusion

Prolonged gestational E₂ deprivation programs a reduction in microvascular flow without altering cardiac function; maternal E₂ prevents this, supporting E₂'s role in …

Yk-4-250 Mitigates Gastrointestinal Radiation Syndrome And Promotes Overall Survival Following Partial Body Radiation Injury, Vidya P. Kumar, Yali Kong, Kan Wang, Asa R. Britton-Jenkins, Stanton Dulan, Landon L. Moore, Debra Saunders, Randal May, Rheal Towner, Sanchita P. Ghosh, Courtney W. Houchen, Milton L. Brown

Department of Biomedical and Translational Sciences Faculty Publications

Acute gastrointestinal radiation syndrome (GI-ARS) is a significant health threat following high-dose ionizing radiation (IR) exposure, leading to severe morbidity and mortality. The syndrome is characterized by gastrointestinal tissue damage caused by angiotensin II (Ang II) and reactive oxygen species (ROS), resulting in impaired GI function, systemic bacteremia, multi-organ failure, and eventual death. Dysregulation of the renin-angiotensin system (RAS) via Ang II exacerbates ROS production through activation of the Angiotensin II type 1 receptor (AT1R). This underscores the need for agents capable of both scavenging ROS and inhibiting AT1R activity. To address this, we developed YK-4-250, a Tempol-conjugated angiotensin receptor …

Expert Consensus On Osteoporosis Risk Management In Patients With Sleep Disorders, Siqi Leng, Jinming Yang, Yuming Jin, Jie Shi, Ye Zhang, Junying Zhou, Lusi Tan, Taomei Li, Peiyan Ni, Kejia Hu, Yuan Shi, Jiamin Liao, Yun Li, Pei Xue, Christian Benedict, Alexandros N. Vgontzas, Michael Furian, Talant Sooronbaev, Naima Covassin, Virend K. Somers, Zhoulong Yu, Hongqiang Sun, Xiao Tan, Jihui Zhang, Yun Kwok Wing, Yue Leng, Larry D. Sanford, Michael V. Vitiello, Katie L. Stone, Rong Ren, Lin Lu, Xiangdong Tang

Department of Biomedical and Translational Sciences Faculty Publications

A rate-limiting step in the prevention and early intervention of osteoporosis is identifying its asymptomatic onset. Accumulating evidence shows that sleep disorders are associated with an increased risk of osteoporosis. Given their early detectable and modifiable nature, integrating sleep disorder management into osteoporosis prevention and care pathways offers a novel approach for enhancing skeletal health. This expert consensus represents a collaborative effort by specialists in sleep medicine and orthopedics from across the world, integrating epidemiological, mechanistic, and interventional evidence to provide general guidance for prevention and clinical practice, and to foster multidisciplinary collaboration in the management of sleep disorders and …

Polyfluoroalkyl Substances And Altered Glucose Homeostasis In Adolescents Following Bariatric Surgery, Elizabeth Costello, Brittney O Baumert, Zhenjiang Li, Vishal Midya, Shudi Pan, Justin R Ryder, Thomas H Inge, Todd M Jenkins, Stephanie Sisley, Stavra A Xanthakos, Anita Courcoulas, Douglas I Walker, Nikos Stratakis, Damaskini Valvi, Scott M Bartell, Angela L Slitt, Rohit Kohli, Sarah Rock, Michele A La Merrill, Sandrah P Eckel, Max T Aung, Rob Mcconnell, David V Conti, Lida Chatzi

Children’s Nutrition Research Center Staff Publications

Objectives: Bariatric surgery is an effective treatment for severe obesity and associated metabolic comorbidities. Exposure to polyfluoroalkyl substance (PFAS) before bariatric surgery may attenuate improvements in glucose metabolism and explain some of the heterogeneity in post-surgery outcomes.

Design: This is an observational cohort study.

Methods: Adolescents (n = 186) enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery study were included. Eight-PFAS congeners were measured in plasma before surgery. Linear and logistic regressions were used to examine cross-sectional associations between log2-transformed PFAS (ng/mL) and fasting glucose, insulin, hemoglobin A1c (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR). Linear mixed …

Alternative Polyadenylation Signatures Distinguish Maladaptive Right Ventricular Remodeling In Pulmonary Hypertension: Implications For Rna-Based Diagnostics And Therapeutics, Janani Subramaniam, Venkata Jonnakuti, Scott D Collum, Sandra Martineau, Kai-Lieh Huang, Sandra Breuils-Bonnet, Andrea L Frump, Bindu H Akkanti, Jayeshkumar A Patel, Manish K Patel, Ismael Salas De Armas, Isabella N Lefebvre, Rajko Radovancevic, Elvin Blanco, Eric J Wagner, Igor Gregoric, Sriram Nathan, Biswajit Kar, Steeve Provencher, Sebastien Bonnet, François Potus, Hari Krishna Yalamanchili, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Increased pulmonary vascular pressures due to vascular remodeling, elevated vascular resistance, and vasoconstriction characterize Pulmonary Arterial Hypertension (PAH). The narrowing of the pulmonary arteries and obstruction of blood flow increase the Right Ventricular (RV) afterload, forcing the RV to undergo structural and functional changes. While adaptive remodeling leads to RV compensation by maintaining function, maladaptive remodeling leads to RV decompensation, characterized by worsening function and eventual failure. At present, there is no effective treatment for these patients as therapies for left ventricular failure are ineffectual, and there are no therapies specifically targeting the RV. Therefore, there is a clear need …

Improving Compliance With Safe Sleep Guidelines For Vulnerable Patients In A Community Safety Net Hospital Neonatal Intensive Care Unit, Andrew Beverstock, Samantha Carlton, Hillary Lee, Thomas Lu, Kelsi Morgan, Ashlee Smith-Patel, Kelli Phillips, Joseph Hagan, Pablo Lohmann, Caraciolo Fernandes, Lisa Owens, Daniela Dinu

Faculty, Staff and Students Publications

Introduction: Modeling safe sleep in the neonatal intensive care unit (NICU) increases the likelihood that parents will follow these practices after discharge. Many NICU infants are put to sleep unsafely, and unsafe sleep practices are the leading cause of nonnatural death among children locally. We created safe sleep standards for infants older than 32 weeks based on national guidelines: infants should be placed supine in a flat, empty crib and should never be swaddled loosely. We aimed to increase the weekly percentage compliance with safe sleep recommendations from a baseline of 58% (0.58 compliant) to 85% (0.85 compliant) by March …

A Review Of Current Research And Barriers To Access: Exploring Disparities In Pediatric Epilepsy Surgery, Nikita Das, Ali A Mohamed, Akshat Katyayan, Meena Vessell

Faculty, Staff and Students Publications

Background: Drug-resistant epilepsy (DRE) impacts at least 30% of pediatric epilepsy patients, adversely affecting neurodevelopment and quality of life, as well as risk of sudden unexplained death in epilepsy (SUDEP). While surgical intervention has proven to be an effective treatment for DRE, disparities in access to surgical care persist. Compared to adults, pediatric patients face unique challenges, including delayed recognition of surgical candidacy, limited access to specialized epilepsy centers, complex care coordination, and socioeconomic barriers.

Summary: This review explores the current state of pediatric epilepsy surgery, highlighting its effectiveness in achieving seizure freedom, improving neurocognitive outcomes, and reducing long-term healthcare …

Sodium Supplementation Algorithm To Promote Growth In Infants Who Are Preterm: Randomized Clinical Trial, Brianna M Liberio, Gregory M Sokol, Hannah Rakow, Kelly Mosesso, Valerie Hole, William W Wong, Shaji K Chacko, Jeffrey L Segar

Faculty, Staff and Students Publications

Objective: Evaluate the effectiveness of an algorithm using urine sodium (Na) concentration to guide dietary Na supplementation compared with standard care to promote growth in infants who are preterm.

Methods: A randomized trial was conducted in 4 neonatal units in Indianapolis, Indiana, involving infants between 250/7 to 296/7 weeks gestation with birthweight > 500 g. Study arms consisted of standard care or use of algorithm beginning at 14 to 17 days postnatal age. The primary outcomes were somatic growth (weight, length, and head circumference) measured by change in Z-score between aged 2 weeks and 36 weeks postmenstrual age (PMA). Secondary outcomes …

Use Of New Tobacco And Nicotine Products As A Harm Reduction Strategy: A Critical Review Of The Evidence, Carlos Andrés Jimenez-Ruiz, José Ignacio De Granda-Orive, Carlos Rábade Castedo, Harold J Farber, Angélica Ocampo, Susana Luhning, Beatriz Raboso-Moreno, Lola Del Puerto-Garcia, Daniel Buljubasich, Manuel Conrado Pacheco-Gallego, José Antonio Castillo-Vizueta, Rosa Mirambeaux-Villalona, Marcos García-Rueda, Juan Antonio Riesco-Miranda, Ángela Ramos-Pinedo, Jaime Signes-Costa, Ledys Blanquicett-Barrios, Eva De Higes-Martinez, Catalina Casillas-Suarez, Concepción Rodríguez-García, Cristina Villar-Laguna, Gloria Francisco-Corral, Esther Pastor-Esplá, Paz Vaquero-Lozano, Francisco Carrion-Valero, Lourdes Cañón-Barroso, Raúl Sandoval-Contreras, Inmaculada Gorordo-Unzueta, Ruth Pitti-Pérez, María Ángeles Muñoz-Vidal, Susana Calvo-Pascual, Eva Cabrera-Cesar, Germán Díaz-Santos, Maribel Cristóbal-Fernández

Faculty, Staff and Students Publications

The sale, distribution, and indiscriminate use of new tobacco and nicotine products have multiplied. The most relevant products are: electronic cigarettes (ECs), heated tobacco (HT), and nicotine pouches (NPs). From the tobacco industry and its related health sectors, and even from some health institutions with no clear influence from this industry, the use of all these devices is being promoted as an excellent harm reduction strategy for those conventional tobacco smokers who do not want to or cannot quit smoking. This paper reviewed the lack of scientific evidence of this strategy.

Gender-Specific Behavior Reductions In Spontaneous Locomotive And Rearing In A Rat Model Of Paclitaxel-Induced Peripheral Neuropathy: A Pilot Study, Serena Jiyeon Kim, Kevin Cao, Patrick M Dougherty, Kathleen E Mcdonough, Saba Javed

Faculty, Staff and Students Publications

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) from agents like paclitaxel causes sensory loss and functional impairment, with limited treatment options. To better model patient-relevant outcomes, we used open field video tracking in rodents to assess gait, anxiety, and exploratory behavior. This approach provides a more comprehensive assessment of CIPN-related deficits beyond pain responses.

Methods and materials: Adult male and female Sprague Dawley rats were given paclitaxel (Taxol; 24 mg/kg cumulative dose) or a vehicle over 8 days. Their distance traveled, time spent in the center and outer zones of the OF test, and rearing behaviors were recorded using a PhenoTyper 4500 …

Beyond Drugs And Surgery: Superselective Adrenal Artery Embolization Redefines Primary Aldosteronism Management-A Systematic Review And Meta-Analysis, Kimia Darmiani, Mehrad Zare, Alisa Mohebbi, Mohammad Mirza-Aghazadeh-Attari, Mohammad Ghasemi Rad, Afshin Mohammadi

Faculty, Staff and Students Publications

Background: Primary aldosteronism (PA) is a leading cause of secondary hypertension associated with increased cardiovascular and cerebrovascular risk. Superselective adrenal artery embolization (SAAE) has emerged as a minimally invasive alternative to adrenalectomy and mineralocorticoid receptor antagonists (MRAs). This systematic review and meta-analysis evaluates the efficacy and safety of SAAE in PA management.

Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library through June 2026 for studies enrolling patients with PA treated by SAAE. Outcomes of interest were changes in blood pressure (BP), biochemical markers (serum potassium, aldosterone, renin activity, and aldosterone-to-renin ratio), clinical and biochemical response rates, daily …

Refining Aicardi Syndrome Diagnostic Criteria: An Expert-Based Consensus Using A Modified Delphi Approach, Silvia Masnada, Valentina De Giorgis, Umberto Carugo, Nadia Bahi-Buisson, Mara Cavallin, Mark Corbett, Manuela Formica, Jozef Gecz, Natalia Petros, Emilio Perucca, Anna Pichiecchio, Paolo Fusar Poli, Elliott H Sherr, Ignatia B Van Den Veyver, Federico Zara, Martin Geroldinger, Pierangelo Veggiotti, Alexis Arzimanoglou

Duncan NRI Faculty and Staff Publications

Background and objectives: Aicardi syndrome (AIC) is a rare neurodevelopmental disorder historically characterised by the presence of chorioretinal lacunae, corpus callosum agenesis, infantile spasms and several supporting features that aid in diagnosis. However, the unclear aetiology and evolving diagnostic tools have led to ongoing reconsideration of the criteria, based on individual approaches. Our study aimed to establish, for the first time, an expert-based consensus on diagnostic criteria for AIC by integrating both existing and novel ones.

Methods: A geographically diverse and multidisciplinary group of expert physicians was invited to participate in a modified Delphi study, to achieve consensus on major, …

Cerebellar Motor And Non-Motor Contributions To Dystonia Pathophysiology And Treatment, Linda H Kim, Cheryl Brandenburg, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia is a complex neurological disorder characterized by sustained or intermittent abnormal movements and/or postures. However, dystonia's non-motor symptoms, particularly the sleep disturbances, are critical yet underexplored concerns that affect all ages. Here, we synthesize current knowledge on the motor and non-motor domains of dystonia, emphasizing the functional interconnections and plasticity within cerebellar motor, cognitive, and sleep-associated circuits to motivate more comprehensive and effective treatments that improve overall quality of life.

Telethon Undiagnosed Disease Program: Structured Approach To Solving Rare Childhood-Onset Genetic Diseases, Annalaura Torella, Manuela Morleo, Carmine Spampanato, Raffaele Castello, Mariateresa Zanobio, Giulio Piluso, Pasquale Di Letto, Maria Elena Onore, Sarah Iffat Rahman, Francesco Musacchia, Michele Pinelli, Giuseppina Vitiello, Giulia De Riso, Angelo Selicorni, Milena Mariani, Cecilia Daolio, Valeria Capra, Marcello Scala, Francesca Nardecchia, Serena Galosi, Mario Mastrangelo, Filippo Manti, Donatella Milani, Corrado Romano, Donatella Greco, Claudia Ciaccio, Stefano D'Arrigo, Arianna De Laurentiis, Antonietta Coppola, Marcella Zollino, Domizia Pasquetti, Federica Francesca L'Erario, Albina Tummolo, Claudia Santoro, Livia Garavelli, Carla Marini, Stefania Bigoni, Alfonsina Tirozzi, Viviana Cetrangolo, Giancarlo Parenti, Diego Di Bernardo, Angela Peron, Silvia Maitz, Andrea Accogli, Gerarda Cappuccio, Sandro Banfi, Giorgio Casari, Andrea Ballabio, Nicola Brunetti-Pierri, Vincenzo Nigro, Telethon Undiagnosed Disease Study Group

Duncan NRI Faculty and Staff Publications

Purpose: Many children with severe genetic disorders remain undiagnosed despite advanced genomic technologies. Early diagnosis is vital for prognosis, genetic counseling, and targeted treatment development. This study aims to increase diagnostic rates in complex pediatric cases and foster research into disease mechanisms.

Methods: Launched in 2016, the Telethon Undiagnosed Diseases Program provides a structured, multicenter approach to rare disease diagnosis. Standardized case submission criteria ensured consistent clinical data collection. Children with severe, multisystemic disorders and prior negative genetic tests were eligible. After case approval, trio-based exome sequencing was performed, with regular reanalysis for unsolved cases until December 2024.

Results: Between …

Tau In Alzheimer’S Disease: Shaping The Future Patient Journey, Catherine J Mummery, Christopher Chen Li-Hsian, Cristian A Lasagna-Reeves, Rik Ossenkoppele, Christopher C Rowe, Douglas W Scharre, Huali Wang, Simon Kyaga, Jeffrey L Cummings

Faculty, Staff and Students Publications

Alzheimer's disease is a complex and multifactorial disease characterized by two key pathological hallmarks: amyloid-beta plaques and tau neurofibrillary tangles. Recent progress has led to the development and approval of disease-targeted therapies for Alzheimer's disease in the form of anti-amyloid-beta monoclonal antibodies. However, findings suggest that amelioration of multiple pathological drivers may be required to maximize clinical effect. An increasing body of evidence suggests that tau is a critical player in Alzheimer's disease pathophysiology, contributing significantly to neurodegeneration and cognitive decline. There are now several tau-targeting drugs in clinical development. In this review, we build on research and advancements in …

Mir-302 Regulates Pancreatic Progenitor Pool And Pancreatic Size, Ziyue Z Yang, Caroline G Snider, Ronald J Parchem

Faculty, Staff and Students Publications

Disruptions in pancreatic development can lead to health issues such as pancreatic agenesis and congenital diabetes mellitus. Understanding pancreatic organogenesis is critical for elucidating disease mechanisms and developing regenerative therapies. The pancreas consists of endocrine and exocrine cells, both of which are derived from multipotent progenitor cells (MPCs). MPC proliferation and differentiation are tightly controlled by multiple mechanisms, including post-transcriptional regulation by miRNAs. However, these regulatory factors are not fully understood. Here, we profiled miRNA expression in MPCs and identified that mir-302 was highly enriched during the earliest stages of pancreatic development. Loss of mir-302 resulted in reduced pancreatic size …

Cerebellar Deep Brain Stimulation Rescues Purkinje Cell Mitochondrial Density In A Genetic Mouse Model Of Cerebellar Ataxia, Lauren N Miterko-Myers, Lauren E Peacoe, Lita Duraine, Zhongyuan Zuo, Roy V Sillitoe

Faculty, Staff and Students Publications

Deep brain stimulation (DBS) improves motor function in a growing list of movement diseases including Parkinson's disease, dystonia, and tremor. There is evidence that DBS may also be effective in ataxia. It is not known why DBS is effective, but modulating cell activity and conferring neuroprotection are hypothesized to underlie its benefits. Understanding the effects of DBS on neurons is paramount to extending its clinical use in the treatment of various motor and non-motor diseases. Here, we stimulated the cerebellum of Car8 waddles (Car8wdl) mice, given the cerebellum's important role in ataxia pathophysiology. Using transmission electron microscopy, we tested the …

Multi-Omics To Study Chronic Respiratory Diseases And Viral Infections, Sobia Idrees, Hao Chen, Tayyaba Sadaf, Saima Firdous Rehman, Matt D Johansen, Keshav Raj Paudel, Gang Liu, Yuting Wang, Malte D Luecken, Elinor Hortle, Ashleigh S Philp, Kurtis F Budden, Matthew O'Rourke, Gerard E Kaiko, Sionne E M Lucas, Joanne L Dickinson, Peter C Allen, Joseph E Powell, Lai-Ying Zhang, Daniel C Chambers, Tamera Corte, Gaetano Caramori, Maor Sauler, Peter A Wark, Janine Gote-Schniering, Mareike Lehmann, Thomas M Conlon, Theodore S Kapellos, Ali Önder Yildirim, Rosa Faner, Shyamali C Dharmage, Craig E Wheelock, Maarten Van Den Berge, Martijn C Nawijn, Francesca Polverino, Gabrielle T Belz, Sanjay H Chotirmall, Leopoldo N Segal, Alen Faiz, Philip M Hansbro

Faculty, Staff and Students Publications

Integrating omics layers reveals complex biological systems, unveiling vital insights into chronic respiratory diseases and COVID-19. This holistic approach is crucial for developing more effective treatments and understanding intricate relationships. https://bit.ly/3VKFzJH

Surface Marker Identification To Capture Live Circulating Tumor Cells In Metastatic Triple-Negative Breast Cancer, Bree M Lege, Khushali J Patel, Brendan Panici, Ping Gong, Michael T Lewis, Matthew J Ellis, Chonghui Cheng

Faculty, Staff and Students Publications

Metastatic triple-negative breast cancer (TNBC) is highly aggressive and lacks targeted therapies. Circulating tumor cells (CTC) are invaluable for monitoring metastatic tumor progression and treatment response but are difficult to capture because of their rarity and heterogeneity. Surface-based staining for live CTCs is essential to preserve RNA quality in single cells, but current markers tend to perform poorly on more mesenchymal tumor cells such as TNBCs. To enhance live TNBC CTC detection, we developed a workflow for live CTC capture and single-cell RNA sequencing (scRNA-seq). Using a mouse model of metastatic TNBC, we identified four new CTC surface markers, AHNAK2, …

Lysine Demethylase 4a Is A Centrosome-Associated Protein Required For Centrosome Integrity And Genomic Stability, Pratim Chowdhury, Xiaoli Wang, Richard I Han, Manga Motrapu, Ashley G Boice, Yuya Nakatani, Sofia Vargas-Hernandez, Julia F Love, Claude Chew, Sandra L Grimm, Dereck Mezquita, Frank M Mason, Elisabeth D Martinez, Cristian Coarfa, Cheryl L Walker, Anna-Karin Gustavsson, Ruhee Dere

Faculty, Staff and Students Publications

Centrosomes play a fundamental role in nucleating and organizing microtubules in the cell and are vital for faithful chromosome segregation and maintenance of genomic stability. Loss of structural or functional integrity of centrosomes causes genomic instability and is a driver of oncogenesis. Here we identify lysine demethylase 4A (KDM4A), an epigenetic 'eraser' of chromatin methyl marks, as a centrosome-localized protein, visualized at the nanometer-scale resolution. We additionally uncovered that KDM4A demethylase enzymatic activity is required to maintain centrosome homeostasis and integrity; a previously unknown functionality unlinked to altered expression of genes regulating centrosome number. We find that KDM4A interacts with …