Digital Commons Network^™

The Loss Of Opa1 Accelerates Intervertebral Disc Degeneration And Osteoarthritis In Aged Mice, Vedavathi Madhu, Miriam Hernandaz-Meadows, Ashley Coleman, Kimheak Sao, Kameron Inguito, Owen Haslam, Paige Boneski, Hiromi Sesaki, Ruteja Barve, John Collins, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Recent studies have highlighted the importance of mitochondria in NP cells and articular chondrocyte health. Since the understanding of mechanisms governing mitochondrial dynamics in these tissues is lacking, we investigated the role of OPA1, a mitochondrial fusion protein, in their homeostasis. OPA1 knockdown in NP cells altered mitochondrial size and cristae shape and increased the oxygen consumption rate. OPA1 governed the morphology of multiple organelles, including peroxisomes, early endosomes and cis-Golgi and loss resulted in the dysregulation of autophagy. Metabolic profiling and

Who Reconstitutes The Chemotherapy? The Educational And Practice Needs Of Oncology Pharmacists In West Africa: A Call For Multidisciplinary Team Approach In Oncology Care., Runcie C.W. Chidebe, Ramatu M. Alabelewe, Krishna Prasad Sapkota, Darlingtina K. Esiaka, Candidus C. Nwakasi, Gloria C. Okwu, Jacinta Emejulu, Adamu A. Umar, Ndifreke Okwuegbunam, Funsho David, Toyosi Adepoju, Agha A. Agha, Ejike S. Ugwu, Simeon C. Aruah, Richard Mshelia, Rob Duncombe, Noel N. Wannang, Peace C. Babalola, R. Donald Harvey, Cindy O'Bryant, Folakemi T. Odedina

Behavioral Science Faculty Publications

PURPOSE: Oncology pharmacists (OPs) play a crucial role in cancer care, treatment, survivorship, and multidisciplinary teams (MDTs). OPs have specialized training in designing, administering, monitoring, and modifying oncology chemotherapy; managing adverse events; and evaluating clinical trials and investigational drugs. Yet, the state of OP has remained largely unknown in the clinical oncology workforce of the West African region. Therefore, this study aimed to understand who reconstitutes chemotherapy and to explain the OP educational and practice needs, challenges, and solutions in Nigeria.

MATERIALS AND METHODS: Using a concurrent embedded mixed method design, 35 OPs completed a questionnaire, and 12 others responded …

The Effect Of Individual Variation On Epidemiological Dynamics: From Super-Spreaders To Landscapes Of Risk, Alexis Shannon Beagle

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Individuals that make up a population always display some level of variation between members. At the smallest scale, individuals always maintain genetic variation, but variation continues to arise at other scales of biological organization from physiological or immunological variation within individuals to variation in behavior between individuals that can be both genetically and environmentally mediated. The role of individual variation is particularly important in the context of infectious diseases because there is strong evidence that infections are highly heterogenous, indicating that patterns of individual variation drive a significant portion of the epidemiological patterns we observe. Individual variation leads to heterogeneity …

Assessing The Risk Of Adverse Obstetric Outcomes And Determinants Among Mothers With Gestational Diabetes Mellitus At Aga Khan University Hospital, Nairobi, Justus Wambugu

Master of Medicine in Obstetrics and Gynecology

Background: Gestational diabetes (GDM) is recognized as a major concern in obstetric care. It is associated with adverse obstetric outcomes including the risk of cesarean delivery, pregnancy-induced hypertension, obstetric hemorrhage, induction of labour, large for gestational age fetus, preterm delivery, and admission to neonatal critical care units. However, there is limited evidence on the magnitude of risk conferred by GDM for various adverse pregnancy outcomes

Objectives: The primary objective of our study was to assess the relative risk for adverse obstetric outcomes associated with GDM in women diagnosed using the WHO-recommended 75g 2-hour oral glucose tolerance test (OGTT), compared to …

Implementing A Team-Based Approach To Reduce Blood Culture Contamination Rates In The Emergency Department: A Quality Improvement Initiative, Melissa Lockhart

Doctor of Nursing Practice Projects

Background: Blood culture contaminations (BCC) present significant risks to patients, including adverse drug reactions and the exacerbation of antibiotic resistance. BCC can also result in millions of dollars in financial burdens for hospitals due to the need for follow-up testing, treatment complications, and antibiotic stewardship efforts. At this facility, the contamination rate in the emergency department (ED) consistently exceeds the national benchmark of 3%. Contributing factors include high patient turnover and increased nursing workloads, which can lead to shortcuts in essential practices such as hand hygiene and skin disinfection before collection.

Purpose: This project aimed to evaluate whether implementing a …

Using The Observational Medical Outcomes Partnership Common Data Model For A Multi-Registry Intensive Care Unit Benchmarking Federated Analysis: Lessons Learned, Aasiyah Rashan, Daniel P Püttmann, Nicolette F De Keizer, Dave A Dongelmans, Ronald Cornet, Otavio Ranzani, Wangari Siika, Matthew Smith, Steve Harris, Abi Beane

Anaesthesiology, East Africa

Objective: Federated analysis is a method that allows data analysis to be performed on similar datasets without exchanging any data, thus facilitating international research collaboration while adhering to strict privacy laws. This study aimed to evaluate the feasibility of using federated analysis to benchmark mortality in 2 critical care quality registry databases converted to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM), describing challenges to and recommendations for performing federated analysis on data transformed to OMOP CDM.

Materials and Methods: To identify as many challenges as possible and to be able to complete the benchmarking phase, …

Childhood Asthma Biomarkers Derived From Plasma And Saliva Exosomal Mirnas, Abdelnaby Khalyfa, Mohit Verma, Meghan M. Alexander, Zhuanhong Qiao, Tammy Rood, Ragini Kapoor, Trupti Joshi, David Gozal, Benjamin D. Francisco

Biomedical Sciences

Asthma, the most common chronic respiratory condition in children, involves airway inflammation, hyper-responsiveness, and frequent exacerbation that worsen the airflow and inflammation. Exosomes, extracellular vesicles carrying microRNAs (miRNAs), play a key role in cell communication alongside other types of communication and are promising markers of asthma severity. This study compares exosomal miRNA and long non-coding RNA (lncRNA) profiles in boys with asthma, focusing on differences between those with normal lung functions and those with severe airflow obstruction. This study enrolled 20 boys aged 9–18 years with asthma, split into two groups based on their lung function. Ten had normal lung …

The Somatic Mosaicism Across Human Tissues Network, Tim H H Coorens, Ji Won Oh, Yujin Angelina Choi, Nam Seop Lim, Boxun Zhao, Adam Voshall, Alexej Abyzov, Lucinda Antonacci-Fulton, Samuel Aparicio, Kristin G Ardlie, Thomas J Bell, James T Bennett, Bradley E Bernstein, Thomas G Blanchard, Alan P Boyle, Jason D Buenrostro, Kathleen H Burns, Fei Chen, Rui Chen, Sangita Choudhury, Harsha V Doddapaneni, Evan E Eichler, Gilad D Evrony, Melissa A Faith, Thomas G Fazzio, Robert S Fulton, Manuel Garber, Nils Gehlenborg, Soren Germer, Gad Getz, Richard A Gibbs, Raquel G Hernandez, Fulai Jin, Jan O Korbel, Dan A Landau, Heather A Lawson, Niall J Lennon, Heng Li, Yan Li, Po-Ru Loh, Gabor Marth, Michael J Mcconnell, Ryan E Mills, Stephen B Montgomery, Pradeep Natarajan, Peter J Park, Rahul Satija, Fritz J Sedlazeck, Diane D Shao, Hui Shen, Andrew B Stergachis, Hunter R Underhill, Alexander E Urban, Melissa W Vondran, Christopher A Walsh, Ting Wang, Tao P Wu, Chenghang Zong, Eunjung Alice Lee, Flora M Vaccarino

Center on Aging Staff Publications

From fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. These postzygotic mutations arise from intrinsic errors in DNA replication and repair, as well as from exposure to mutagens. Somatic mutations have been implicated in some diseases, but a fundamental understanding of the frequency, type and patterns of mutations across healthy human tissues has been limited. This is primarily due to the small proportion of cells harbouring specific somatic variants within an individual, making them more challenging to detect than inherited variants. Here we describe the Somatic Mosaicism across Human Tissues …

Clinically Validated Graphical Approaches Identify Hepatosplenic Multimorbidity In Individuals At Risk Of Schistosomiasis, Yin-Cong Zhi, Simon Mpooya, Narcis Kabatereine, Betty Nabatte, Christopher Opio, Narcis Kabatereine, Goylette Chami

Internal Medicine, East Africa

The global burden of multimorbidity is increasing yet poorly understood, owing to insufficient methods for modelling complex systems of conditions. In particular, hepatosplenic multimorbidity has been inadequately investigated. From 17 January to 16 February 2023, we examined 3186 individuals aged 5–92 years from 52 villages across Uganda within the SchistoTrack Cohort. Point-of-care B-mode ultrasound was used to assess 45 hepatosplenic conditions within the context of schistosomiasis (Schistosoma mansoni). Three graph learning methods for representing hepatosplenic multimorbidity were compared. Thresholds for including graph edges were found using graph kernels and tested with graph neural networks to assess predictive utility for unobserved …

A Brief Guide To Statistical Analysis Of Grouped Data In Preclinical Research, Colby J Vorland, Lilian Golzarri-Arroyo, David B Allison

Children’s Nutrition Research Center Staff Publications

Clustering and nesting (C&N) arise in many preclinical studies such as when animals are group-housed, share litters, or in cell culture. Ignoring C&N undermines the validity of analyses. We explain how C&N arise and valid designs and analyses.

To Pause With A Cliffhanger Or A Temporary Closure? The Differential Impact Of Serial Versus Episodic Narratives On Children's Physical Activity Behaviors, Amy Shirong Lu, Melanie C Green, Caio Victor Sousa, Jungyun Hwang, I-Min Lee, Debbe Thompson, Tom Baranowski

Children’s Nutrition Research Center Staff Publications

Research has supported the effectiveness of narratives for promoting health behavior, but different narrative presentation formats (serial vs. episodic) have seldom been compared. Suspense theories suggest that serial narratives, which do not provide a full resolution at the end of an episode, may create higher motivation for continued engagement with a story. Forty-four 8 to 12-year-old children were randomly assigned to watch an animation series designed for an existing active video game in which the plot was delivered either continuously across multiple episodes (serial) or in multiple yet relatively independent self-contained episodes (episodic). Controlling for social desirability, children who watched …

Clinico-Epidemiological Characteristics Of Cerebral Venous Sinus Thrombosis In Kenya: A Retrospective Case Series, Taby Siika, Jaskirat Sokhi, Juzar Hooker, Sheila Waa, Anne Mwirigi, Jasmit Shah, Dilraj Sokhi

Internal Medicine, East Africa

Background: Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke that is more common in young, especially female, adults and can be challenging to diagnose due to its frequently non-specific presentation and diverse risk factors. Most cases are idiopathic, and international guidelines do not recommend routine investigations for underlying thrombophilia. Timely diagnosis, with prompt neuroimaging and guideline-based treatment, leads to good outcomes. However, in the literature on CVST from sub-Saharan Africa, the gap is substantial, with the few cases described as being related to systemic and/or brain infections. We describe here the largest cohort of CVST from the …

C-Terminal Frameshift Variants In Gpkow Are Associated With A Multisystemic X-Linked Disorder, Jung-Wan Mok, Laura Mackay, Maria Blazo, Elizabeth Mizerik, Jozef Gecz, Renee Carroll, Mathilde Nizon, Sophie Rondeau, Madeleine Joubert, Silvestre Cuinat, Wallid Deb, Fernanda Valle Sirias, Monika Weisz-Hubshman, Shamika Ketkar, Urszula Polak, Alyssa A Tran, Debra Kearney, Neil A Hanchard, Oguz Kanca, Michael F Wangler, Hugo J Bellen, Brendan H Lee, Shinya Yamamoto, Keren Machol

Duncan NRI Faculty and Staff Publications

Purpose: GPKOW, a gene on the X-chromosome, encodes a nuclear RNA-binding protein important in messenger RNA (mRNA) processing as a spliceosome subunit. This work aims to establish GPKOW as a disease-associated gene.

Methods: We describe 3 males from 2 unrelated families with hemizygous frameshift variants affecting the last exon of GPKOW p.(Arg441SerfsTer30) and p.(Ser444GlufsTer28). The effect of p.(Ser444GlufsTer28) on gene expression was evaluated in patient's fibroblasts. In vivo studies in Drosophila melanogaster targeting the sole GPKOW fly ortholog, CG10324 (Gpkow) were performed.

Results: Clinical presentations included intrauterine growth restriction, microcephaly/microencephaly, and eye, brain, skin, and skeletal abnormalities. Heterozygote females presented …

A Phase 2 Trial Of Short-Term Intravenous N-Acetylcysteine In Biliary Atresia After Kasai Portoenterostomy, Sanjiv Harpavat, Kristin A Borovsky, Michael E Scheurer, Laurel Cavallo, Franca E Erhiawarie, Sanjeev Vasudevan, Adam M Vogel, Dana Cerminara, Elizabeth M Tessier, Kalyani R Patel, Sridevi Devaraj, Benjamin L Shneider

Center for Medical Ethics and Health Policy Staff Publications

Background: For infants with biliary atresia, the only treatment that can establish bile flow and delay need for liver transplant is the Kasai portoenterostomy (KP). Unfortunately, the KP has variable success. In this study, we hypothesized that intravenous N-acetylcysteine (IV NAC) treatment following KP would improve bile flow.

Methods: This was a phase 2 study following the two-stage "minimax" trial design. Participants received IV NAC (150 mg/kg/day) for 7 days after KP, and the primary endpoint was achieving total serum bile acids (TSBA) ≤10 μmol/L within 24 weeks of KP. Secondary endpoints were clinical markers and the occurrence of sentinel …

Functional Regulation Of Macrophages By Ces1d-Mediated Lipid Signaling In Immunometabolism, Long J Shao, Fathima Elizondo, Feng Gao, Rabie Habib, Xin Li, Katherine Pham, Jazmin Ysaguirre, Maryam Elizondo, Shirindokht Shirazi, Kristin L Eckel-Mahan, Sean Hartig, Huaizhu Wu, Kai Sun

Faculty, Staff and Student Publications

Objective: Macrophage accumulation in metabolically active tissues during obesity is common in both animals and humans, but the lipid signaling mechanisms that trigger macrophage inflammation remain unclear. This study investigates the role of Ces1d, an unconventional lipase, in regulating macrophage inflammation under nutritional stress.

Methods: A myeloid-specific Ces1d knockout (LysM-Cre-Ces1d floxed/floxed, KO) mouse model was used for the studies. For in vitro tests, bone marrow-derived macrophages (BMDMs) from control (Ces1d floxed/floxed, WT) and KO mice were assessed for migration, polarization, and activation. For in vivo experiments, WT and KO mice were induced to obesity via a high-fat diet (HFD) and …

Novel Validation Of Hdr Brachy Therapy Dosimetry For Cervical Cancer Using Egs_Brachy Monte Carlo Simulations: A Comparative Analysis With Oncentra Treatment Planning System., Duong Thanh Tai, Nguyen Thi Anh Thu, Tran Thien Thanh, Pham Anh Tuan, Marc J P Chamberland, Peter Sandwall, David Bradley, James C L Chow

Oncology Articles

PURPOSE: This study aims to validate HDR brachytherapy dosimetry for cervical cancer patients utilizing the egs_brachy Monte Carlo (MC) simulation.

METHODS: Three cervical cancer patients treated with

RESULTS: TPS-calculated doses were greater than those obtained from MC simulations. For the CTV, the median percentage differences were 7.9% (Q1: 6.4%, Q3: 9.8%; range: 0.4%-10.4%) for D

CONCLUSION: CTV and critical organ doses calculated by the TPS were consistently greater than those obtained from MC simulations. This suggests that the TPS may overestimate dose distributions, especially in heterogeneous regions like the pelvis. These results emphasize the need for continued validation of TPS …

Airway Management During Emergent Laparotomy In A Patient With Subglottic Stenosis And Unilateral True Vocal Cord Paralysis: A Case Report., Rayyan Bhutta, Ali Osman, Connor Henn, Hameed H Salah, Samir Patel

Surgery Articles

This case report describes the airway course of a 52-year-old male who required emergent exploratory laparotomy for suspected gastrointestinal perforation. The patient had underlying subglottic stenosis and unilateral vocal cord paralysis, as well as a history of significant cardiopulmonary disease. Attempts at intubation using standard tube sizes were unsuccessful. A 6.0 endotracheal tube was eventually passed beyond a point of resistance, allowing the operation to proceed. He remained intubated after surgery and was successfully extubated several days later. The report emphasizes the need for adaptable airway plans and highlights the constraints that may arise during urgent operative care.

Clinical Assessment On Days 1-14 For The Characterization Of Traumatic Brain Injury: Recommendations From The 2024 Ninds Traumatic Brain Injury Classification And Nomenclature Initiative Clinical/Symptoms Working Group, David K Menon, Noah D Silverberg, Adam R Ferguson, Thomas J Bayuk, Shubhayu Bhattacharyay, David L Brody, Scott A Cota, Ari Ercole, Anthony Figaji, Guoyi Gao, Christopher C Giza, Fiona Lecky, Rebekah Mannix, Ana Mikolić, Kasey E Moritz, Claudia S Robertson, Abel Torres-Espin, Spyridoula Tsetsou, John K Yue, Hibah O Awad, Kristen Dams-O'Connor, Adele Doperalski, Andrew I R Maas, Michael A Mccrea, Nsini Umoh, Geoffrey T Manley

Faculty, Staff and Students Publications

The current classification of traumatic brain injury (TBI) primarily uses the Glasgow Coma Scale (GCS) to categorize injuries as mild (GCS 13-15), moderate (GCS 9-12), or severe (GCS ≤8). However, this system is unsatisfactory, as it overlooks variations in injury severity, clinical needs, and prognosis. A recent report by the National Academies of Sciences, Engineering, and Medicine (USA) recommended updating the classification system, leading to a workshop in 2024 by the National Institute of Neurological Disorders and Stroke. This resulted in the development of a new clinical, biomarker, imaging, and modifier (CBI-M) framework, with input from six working groups, including …

Multiple Subcortical And Subcortico-Cortico Dynamic Network Reconfigurations Characterize Focal-To-Bilateral Tonic-Clonic Seizures, Shilpi Modi, A. Ankeeta, Walter Hinds, Michael R. Sperling, Xiaosong He, Joseph I. Tracy

Department of Neurology Faculty Papers

Temporal lobe epilepsy (TLE) is the most common focal epilepsy, with focal to bilateral tonic-clonic seizures (FBTCS+) a more severe form of the disorder. Evidence has underscored the critical role of the thalamus, mesial temporal region, basal ganglia and cerebellum, along with the cortex, in the propagation, termination, and modulation of seizure activity. We examined time variant patterns of interaction within and between 7 cortical and 4 subcortical systems in 55 healthy controls and 56 patients with TLE (n = 40 with FBTCS+ and 15 without), isolating those patterns most distinctive of FBTCS+ utilizing tools from dynamic network neuroscience on …

Cardiac Rhythm Devices In Heart Failure With Reduced Ejection Fraction – Role, Timing, And Optimal Use In Contemporary Practice European Journal Of Heart Failure Expert Consensus Document, Biykem Bozkurt, Wilfried Mullens, Christophe Leclercq, Andrea M Russo, Gianluigi Savarese, Michael Böhm, Loreena Hill, Koichiro Kinugawa, Naoki Sato, William T Abraham, Antoni Bayes-Genis, Alexandre Mebazaa, Giuseppe M C Rosano, Shelley Zieroth, Cecilia Linde, Javed Butler

Faculty, Staff and Students Publications

Guidelines for management of heart failure with reduced ejection fraction (HFrEF) emphasize personalized care, patient engagement, and shared decision-making. Medications and cardiac rhythm management (CRM) devices are recommended with a high level of evidence. However, there are significant disparities: patients who could benefit from devices are frequently referred too late or not at all. Misconceptions about device therapy and the notion that the needs of patients (especially the prevention of sudden cardiac death) can now be met by expanding drug therapies may play a role in these disparities. This state-of-the-art review is produced by members of the DIRECT HF initiative, …

Cytokine Release Syndrome And Neurotoxicity Following Cd19 Car-T In B-Cell Lymphoma, Roni Shouval, Christopher Strouse, Soyoung Kim, Temitope Oloyede, Sairah Ahmed, Farrukh T Awan, Danny Luan, Veronika Bachanova, Talha Badar, Merav Bar, Pere Barba, Amer M Beitinjaneh, Amanda Cashen, Bhagirathbhai Dholaria, Mahmoud Elsawy, Siddhartha Ganguly, Praveen Ramakrishnan Geethakumari, Uri Greenbaum, Hamza Hashmi, Laquisa C Hill, Michael D Jain, Tania Jain, Partow Kebriaei, Adam S Kittai, Frederick L Locke, Premal D Lulla, Elena Mead, Joseph P Mcguirk, Alberto Mussetti, Taiga Nishihori, Amanda L Olson, Martina Pennisi, Miguel-Angel Perales, Peter A Riedell, Wael Saber, Abu-Sayeef Mirza, Margarida Magalhaes-Silverman, Elizabeth J Shpall, Mohamed Sorror, Kitsada Wudhikarn, Cameron J Turtle, Amy Moskop, Marcelo C Pasquini

Faculty, Staff and Students Publications

Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for relapsed-refractory large B-cell lymphoma (LBCL). However, toxicities, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), remain significant concerns. Analyze temporal trends, risk factors, and associations between these toxicities and their severity. In this registry study by the Center for International Blood and Marrow Transplant Research, we studied CRS and ICANS in 1916 LBCL patients treated with commercial CAR-T therapies (axicabtagene ciloleucel 74.9%, tisagenlecleucel 25.1%) between 2018 and 2020. Outcomes include development of CRS/ICANS, timing and severity according to ASTC grading, overall survival (OS). Risk …

Implementing A Stakeholder-Informed Approach For Standardized Collection Of Sexual Orientation And Gender Identity Data: Lessons Learned At A Matrix Comprehensive Cancer Center, Susan L Parker, Montserrat Ayala-Ramirez, Jane R Montealegre, Michael E Scheurer

Faculty, Staff and Students Publications

This brief report describes takeaways from the implementation of sexual orientation and gender identity (SOGI) data collection within a matrix comprehensive cancer center. Implementation of standardized and parsimonious SOGI data collection practices is a strategy recommended to improve our understanding of the cancer experiences among sexual and gender minority (SGM) populations. However, interventions are rarely sustained in routine practice without an organized program to support their implementation. We used a stakeholder-engaged approach to integrate a SOGI questionnaire in the electronic health record (EHR) at Dan L Duncan Comprehensive Cancer Center (DLDCCC)-affiliated adult oncology clinics and evaluate its feasibility, acceptability, and …

Rural Cancer Survivors' Perceived Delays In Seeking Medical Attention, Diagnosis And Treatment: Findings From A Large Qualitative Study, Alyssa Taglieri-Sclocchi, Ingrid Bindicsova, Susannah K. Ayre, Michael Ireland, Sonja March, Fiona Crawford-Williams, Suzanne Chambers, Jeff Dunn, Belinda C. Goodwin, Elizabeth A. Johnston

Research outputs 2022 to 2026

Aims: To investigate rural cancer survivors' self-reported reasons for perceived delays in initial cancer detection and treatment. Methods: Within a cohort study, adult cancer survivors who had travelled > 50 km for cancer care, staying at subsidised accommodation lodges in city centres in Queensland, Australia, were invited to complete a structured interview on perceived delays in: (i) seeking medical attention, (ii) receiving their diagnosis and (iii) commencing treatment. Content analysis was used to map self-reported reasons for perceived delays at each step, which were then categorised based on the perceived source: (i) personal, (ii) healthcare professional, (iii) healthcare system or (iv) …

Inhibition Of Srebp-1c Rescues Hepatic Cyp7b1 Expression And Bile Acid Synthesis In Malnourished Mice, Xiaoyang Wan, Krishnakant G Soni, Jong Min Choi, Sun Yun Jung, Margaret E Conner, Geoffrey A Preidis

Faculty, Staff and Students Publications

Malnutrition decreases intestinal bile acids, resulting in inefficient nutrient absorption and impaired catch-up growth. Mechanisms by which bile acid depletion occurs in malnutrition are unknown. Using a mouse model of early-life malnutrition, we explored bile acid homeostasis, focusing on transcriptional repression of CYP7B1, a rate-limiting enzyme in the alternative pathway of bile acid biosynthesis, by SREBP-1c, a master regulator of lipid metabolism. Mice were maintained on a low-protein low-fat or isocaloric control chow until eight weeks of age when livers were harvested for proteome profiling, western blot, RT-qPCR, and chromatin immunoprecipitation. Cultured hepatocytes and mice were treated with the SREBP-1c …

Deficits In Mitochondrial Dynamics And Iron Balance Result In Templated Insertions, Jordan Fox, Yang Yu, Yang Yu, Pilendra Thakre, Chloe Fox, Qian Li, Yunxia Wang, Adam Hughes, Xin Wang, Kaifu Chen, Grzegorz Ira

Faculty, Staff and Students Publications

Mitochondrial membrane dynamics control the shape, number, and distribution of mitochondria and regulate energy production and cell health. In a screen for yeast mutants with increased levels of templated insertions (~10-1000 bp) in the nuclear genome, we identified mitochondrial fusion deficient mutants (mgm1Δ, ugo1Δ, fzo1Δ). We found that fusion mutants activate the iron regulon, have decreased iron-sulfur clusters (ISCs), and increased DNA damage, suggesting a role of iron homeostasis in preventing insertions. Consistently, a secondary screen found mutants affecting iron-sulfur cluster production (yfh1Δ, grx5Δ), vacuolar iron storage (ccc1Δ) or general iron homeostasis (aft1Δ) to exhibit high insertion levels. Treatment with …

Figo Position Statement: Gamete Donations, Laurie Henry, Aris Antsaklis, Dov Feldberg, Jaideep Malhotra, Suchitra Pandit, Carlos Salazar, Alex Vidaeff, Rafal Zadykowicz, M Louise Hull, Nikhil Purandare

Faculty, Staff and Students Publications

Gamete donation has become a crucial part of Assisted Reproductive Technologies (ARTs), providing hope to individuals, including those who may have no other option for parenthood. This process comes with a wide range of ethical, medical, and legal challenges that need to be carefully addressed to protect the well-being and rights of all parties involved: donors, recipients, and offspring. Navigating these complexities requires strict ethical standards, robust regulatory frameworks, and international collaboration. By standardizing these, the field of gamete donation can continue to develop while ensuring that all parties are well informed and safeguarded. This paper explores the ethical concerns …

A Survey Study Of Roadblocks In Translational Science, Fasiha Kanwal, Christopher I Amos, Katherine H Sippel, Claudia Neuhauser, Ariel Harrison, Mary E Dickinson, Charles Minard, Bettina M Beech

Faculty, Staff and Students Publications

Clinical and translational science needs to address roadblocks to the translational processes. We conducted a survey at two institutions, a private medical school and a large public university, to understand the frequency and distribution of barriers and roadblocks to research. We reviewed the literature to compile a pool of barriers and roadblocks and convened a panel of relevant stakeholders to develop a 20-item questionnaire. Survey respondents were asked to select and prioritize the five leading clinical and translational roadblocks, provide information regarding their academic degrees and rank/position, complete open-ended items regarding their areas of research, and optionally add additional remarks …

Genomic Reporting Practices Across 5 Molecular Disciplines: A Study From The College Of American Pathologists, Larissa V Furtado, Annette S Kim, Ann M Moyer, Joel T Moncur, Rena R Xian, Angshumoy Roy, Avni B Santani, Yassmine Akkari, Karl V Voelkerding, Rhona J Souers, Jaimie Halley, Glenn E Palomaki

Faculty, Staff and Students Publications

Context.—: Genomic reports are primarily organized in a narrative and unstructured format with variations in content and format. Regulatory requirements and professional guidelines for genetic test reporting exist but provide little guidance for effective communication of information.

Objective.—: To assess clinical genomic reporting practices across 5 disciplines within molecular diagnostics, including germline, somatic solid tumors, somatic hematologic malignancies, pharmacogenomics, and prenatal cell-free DNA screening.

Design.—: Reporting practices were assessed by using a structured review of clinical genomic reports from multiple laboratories in 5 molecular disciplines spanning different practice settings. Report content was reviewed by the presence/absence of from 27 to …

Reduction Of Neuronal Activity Mediated By Blood-Vessel Regression In The Adult Brain, Xiaofei Gao, Xing-Jun Chen, Meng Ye, Jun-Liszt Li, Nannan Lu, Di Yao, Bo Ci, Fei Chen, Lijun Zheng, Yating Yi, Shiwen Zhang, Zhanying Bi, Xinwei Gao, Yuanlei Yue, Tingbo Li, Jiafu Lin, Ying-Chao Shi, Kaibin Shi, Nicholas E Propson, Yubin Huang, Katherine Poinsatte, Zhaohuan Zhang, Dale B Bosco, Shi-Bing Yang, Ralf H Adams, Volkhard Lindner, Fen Huang, Long-Jun Wu, Hui Zheng, Simon Hippenmeyer, Ann M Stowe, Bo Peng, Marta Margeta, Qingchun Guo, Xiaoqun Wang, Qiang Liu, Jakob Körbelin, Martin Trepel, Hui Lu, Guoen Cai, Bo O Zhou, Bo Shen, Ying-Mei Lu, Wenzhi Sun, Jie-Min Jia, Feng Han, Hu Zhao, Robert M Bachoo, Woo-Ping Ge

Center on Aging Staff Publications

The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and …

Muscle Rev-Erb Controls Time-Dependent Adaptations To Chronic Exercise In Mice, Jidong Liu, Fang Xiao, Abhinav Choubey, Udhaya Kumar S, Yanxiang Wang, Sungguan Hong, Tingting Yang, Husniye Gul Otlu, Ege Sanem Oturmaz, Emanuele Loro, Yuxiang Sun, Pradip Saha, Tejvir S Khurana, Li Chen, Xinguo Hou, Zheng Sun

Center on Aging Staff Publications

The best time of the day for chronic exercise training and the mechanism underlying the timing effects is unclear. Here, we show that low-intensity, low-volume treadmill training in mice before sleep yields greater benefits than after waking for muscle contractile performance and systemic glucose tolerance. Baseline muscle performance also exhibits diurnal variations, with higher strength but lower endurance before sleep than after waking. Muscle-specific knockout of circadian clock genes Rev-erbα/β (Rev-MKO) in male mice eradicates the diurnal variations in both training and baseline conditions without affecting muscle mass, mitochondrial content, food intake, or spontaneous activities. Multi-omics and metabolic measurements reveal …