Genetic Phenomena Commons^™

A Case Of Successful Treatment Of Recurrent Urinary Tract Infection By Extended-Spectrum Β-Lactamase Producing Klebsiella Pneumoniae Using Oral Lyophilized Fecal Microbiota Transplant, Naomi Bier, Blake Hanson, Zhi-Dong Jiang, Herbert L Dupont, Cesar A Arias, William R Miller

Faculty, Staff and Student Publications

Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae UTIs in a patient with an ileal conduit and urostomy. In the 18 months after FMT, the patient had not experienced new infections with ESBL-producing organisms. The urine and stool microbiomes of the patient were tracked before and post-FMT using 16s RNA sequencing with measurement of α-diversity. Sequencing of …

Editorial: The Interplay Between Microbiota And Allergen In Shaping Respiratory Mucosa Immunity: Role In Development Of Asthma, Zhenwei Xia, Wenwei Zhong, Min Wu, Scott E Evans

Faculty, Staff and Student Publications

No abstract provided.

Targeted Genomic Sequencing Of Tsc1 And Tsc2 Reveals Causal Variants In Individuals For Whom Previous Genetic Testing For Tuberous Sclerosis Complex Was Normal, Hannah D West, Mark Nellist, Rutger W W Brouwer, Mirjam C G N Van Den Hout-Van Vroonhoven, Luiz Gustavo Dufner De Almeida, Femke Hendriks, Peter Elfferich, Meera Raja, Peter Giles, Rosa M Alfano, Angela Peron, Yves Sznajer, Liesbeth De Waele, Anna Jansen, Marije Koopmans, Anneke Kievit, Laura S Farach, Hope Northrup, Julian R Sampson, Laura E Thomas, Wilfred F J Van Ijcken

Faculty, Staff and Student Publications

Tuberous sclerosis complex (TSC) is caused by inactivating variants in TSC1 and TSC2. Somatic mosaicism, as well as the size and complexity of the TSC1 and TSC2 loci, makes variant identification challenging. Indeed, in some individuals with a clinical diagnosis of TSC, diagnostic testing fails to identify an inactivating variant. To improve TSC1 and TSC2 variant detection, we screened the TSC1 and TSC2 genomic regions using targeted HaloPlex custom capture and next-generation sequencing (NGS) in genomic DNA isolated from peripheral blood of individuals with definite, possible or suspected TSC in whom no disease-associated variant had been identified by previous …

Epigenetic Aging In Psychiatry: Clinical Implications And Therapeutic Opportunities, Camila N C Lima, Gabriel R Fries

Faculty, Staff and Student Publications

No abstract provided.

Financial Toxicity In Cancer Patients And Subsequent Risk Of Repeat Acute Care Utilization, Julia J Shi, J Alberto Maldonado, Chi-Fang Wu, Susan K Peterson, Ying-Shiuan Chen, Kevin Diao, Robert J Volk, Sharon H Giordano, Ya-Chen T Shih, Kelsey Kaiser, Grace L Smith

Faculty, Staff and Student Publications

Background: Acute care (AC) visits by cancer patients are costly sources of healthcare resources and can exert a financial burden of oncology care both for individuals with cancer and healthcare systems. We sought to identify whether cancer patients who reported more severe initial financial toxicity (FT) burdens shouldered excess risks for acute care utilization.

Methods: In 225 adult patients who participated in the Economic Strain and Resilience in Cancer (ENRICh) survey study of individuals receiving ambulatory cancer care between March and September 2019, we measured the baseline FT (a multidimensional score of 0-10 indicating the least to most severe global, …

Leveraging A Genetically-Informative Study Design To Explore Depression As A Risk Factor For Type 2 Diabetes: Rationale And Participant Characteristics Of The Mood And Immune Regulation In Twins Study, Briana Mezuk, Kristen Kelly, Erica Bennion, Jeannie B Concha

Faculty, Staff and Student Publications

Background: Comorbidity between depression and type 2 diabetes is thought to arise from the joint effects of psychological, behavioral, and biological processes. Studies of monozygotic twins may provide a unique opportunity for clarifying how these processes inter-relate. This paper describes the rationale, characteristics, and initial findings of a longitudinal co-twin study aimed at examining the biopsychosocial mechanisms linking depression and risk of diabetes in mid-life.

Methods: Participants in the Mood and Immune Regulation in Twins (MIRT) Study were recruited from the Mid-Atlantic Twin Registry. MIRT consisted of 94 individuals who do not have diabetes at baseline, representing 43 twin pairs …

Methodological Considerations In Pisces 3: A Randomized, Placebo-Controlled Study Of Intracerebral Stem Cells In Subjects With Disability Following An Ischemic Stroke, Daniel T Laskowitz, Keith W Muir, Sean I Savitz, Lawrence R Wechsler, Julie G Pilitsis, Scott Y Rahimi, Richard L Beckman, Vincent Holmes, Peng R Chen, Laura Juel, Deborah Koltai, Brad J Kolls

Faculty, Staff and Student Publications

Background and hypothesis: At present, there are no medical interventions proven to improve functional recovery in patients with subacute stroke. We hypothesize that the intraparenchymal administration of CTX0E03, a conditionally immortalized neural stem cell line, linked with a standardized rehabilitation therapy regimen for the upper limb, would improve functional outcomes in patients 6-12 months after an index ischemic stroke.

Study design: PISCES III was designed as a multicenter prospective, sham-controlled, outcome-blinded randomized clinical trial. Eligibility required a qualifying ischemic stroke 6-12 months prior to surgical intervention. Patients must be between 35 and 75 years of age and have residual moderate …

Editorial: Prion-Like Transmission Of Pathogenic Proteins In Neurodegenerative Diseases: Structural And Molecular Bases, Victor Banerjee, Fei Wang, Daniela Sarnataro, Claudio Soto

Faculty, Staff and Student Publications

No abstract provided.

Effects Of Heterozygous Deletion Of Autism-Related Gene Cullin-3 In Mice, Qiang-Qiang Xia, Angela K Walker, Chenghui Song, Jing Wang, Anju Singh, James A Mobley, Zhong X Xuan, Jeffrey D Singer, Craig M Powell

Faculty, Staff and Student Publications

Autism Spectrum Disorder (ASD) is a developmental disorder in which children display repetitive behavior, restricted range of interests, and atypical social interaction and communication. CUL3, coding for a Cullin family scaffold protein mediating assembly of ubiquitin ligase complexes through BTB domain substrate-recruiting adaptors, has been identified as a high-risk gene for autism. Although complete knockout of Cul3 results in embryonic lethality, Cul3 heterozygous mice have reduced CUL3 protein, demonstrate comparable body weight, and display minimal behavioral differences including decreased spatial object recognition memory. In measures of reciprocal social interaction, Cul3 heterozygous mice behaved similarly to their wild-type littermates. In area …

Mri And Amino Acid Pet Detection Of Whole-Brain Tumor Burden, Peng Chen, Matthew L Scarpelli, Debbie R Healey, Shwetal Mehta, C Chad Quarles

Faculty, Staff and Student Publications

Background: [18F]fluciclovine amino acid PET has shown promise for detecting brain tumor regions undetected on conventional anatomic MRI scans. However, it remains unclear which of these modalities provides a better assessment of the whole brain tumor burden. This study quantifies the performance of [18F]fluciclovine PET and MRI for detecting the whole brain tumor burden.

Methods: Thirteen rats were orthotopically implanted with fluorescently transduced human glioblastoma cells. Rats underwent MRI (T1- and T2-weighted) and [18F]fluciclovine PET. Next brains were excised, optically cleared, and scanned ex vivo with fluorescence imaging. All images were co-registered using a novel landmark-based registration to enable a …

A Cross-Sectional Study To Test Equivalence Of Low- Versus Intermediate-Flip Angle Dynamic Susceptibility Contrast Mri Measures Of Relative Cerebral Blood Volume In Patients With High-Grade Gliomas At 15 Tesla Field Strength, Mark S Shiroishi, Dane Weinert, Steven Y Cen, Bino Varghese, Timothy Dondlinger, Melissa Prah, Jesse Mendoza, Sina Nazemi, Nima Ameli, Negin Amini, Salman Shohas, Shannon Chen, Bavrina Bigjahan, Gabriel Zada, Thomas Chen, Josh Neman-Ebrahim, Eric L Chang, Frances E Chow, Zhaoyang Fan, Wensha Yang, Frank J Attenello, Jason Ye, Paul E Kim, Vishal N Patel, Alexander Lerner, Jay Acharya, Leland S Hu, C Chad Quarles, Jerrold L Boxerman, Ona Wu, Kathleen M Schmainda

Faculty, Staff and Student Publications

INTRODUCTION: 1.5 Tesla (1.5T) remain a significant field strength for brain imaging worldwide. Recent computer simulations and clinical studies at 3T MRI have suggested that dynamic susceptibility contrast (DSC) MRI using a 30° flip angle ("low-FA") with model-based leakage correction and no gadolinium-based contrast agent (GBCA) preload provides equivalent relative cerebral blood volume (rCBV) measurements to the reference-standard acquisition using a single-dose GBCA preload with a 60° flip angle ("intermediate-FA") and model-based leakage correction. However, it remains unclear whether this holds true at 1.5T. The purpose of this study was to test this at 1.5T in human high-grade glioma (HGG) …

Global Research Trends And Prospects Related To Tumor Microenvironment Within Triple Negative Breast Cancer: A Bibliometric Analysis, Peiting Li, Jun Li, Xiaofei Tong, Zhenyang Xiao, Wuliang Diao, Chi Zhong, Jianda Zhou, Wei Wu

Faculty, Staff and Student Publications

Background and aims: The tumor microenvironment (TME) has pivotal parts within multiple tumor models of onset/progression, such as triple-negative breast cancer (TNBC). This bibliometric analysis was developed to explore trends and research niches revolving around TME in TNBC.

Methods: Web of Science Core Collection was queried for identifying studies linked with TME in TNBC, after which the VOSviewer, CiteSpace, and R software programs were used to conduct bibliometric analyses and to generate corresponding visualizations.

Results: In total, this study included 1,604 studies published from 2005-2023. The USA and China exhibited the highest numbers of citations, and the research institutions with …

Editorial: Ovarian Cancer-Targeted Medication: Parp Inhibitors, Anti-Angiogenic Drugs, Immunotherapy, And More, Zhi-Bin Wang, Dan Liu, Guang Lei, Zhao-Qian Liu, Nayiyuan Wu, Jing Wang

Faculty, Staff and Student Publications

No abstract provided.

Pseudohypoadrenalism, A Subclinical Cortisol Metabolism Disorder In Hyperuricemia, Ruixia Bao, Beibei Chen, Jujie Pan, Alexander Wang, Haiyang Yu, Qian Chen, Yi Zhang, Tao Wang

Faculty, Staff and Student Publications

Background: Hyperuricemia is a known risk factor of lipid metabolism disorder. However, the mechanisms have not been fully understood.

Methods: The serum samples from hyperuricemia subjects were used to analyze the correlation between serum uric acid and clinical characteristics. Hyperuricemia mice induced by potassium oxonate (PO) and adenine were used to explore glucocorticoid metabolism.

Results: In hyperuricemia patients, the levels of serum uric acid were positively correlated with the levels of γ-glutamyltransferase, associated with a cortisol metabolism disorder. In hyperuricemia state, the adrenal glands failed to respond to adrenocorticotropic hormone properly, leading to low cortisol, but not corticosterone production, and …

Combining Small Angle X-Ray Scattering (Saxs) With Protein Structure Predictions To Characterize Conformations In Solution, Naga Babu Chinnam, Aleem Syed, Greg L Hura, Michal Hammel, John A Tainer, Susan E Tsutakawa

Faculty, Staff and Student Publications

Accurate protein structure predictions, enabled by recent advances in machine learning algorithms, provide an entry point to probing structural mechanisms and to integrating and querying many types of biochemical and biophysical results. Limitations in such protein structure predictions can be reduced and addressed through comparison to experimental Small Angle X-ray Scattering (SAXS) data that provides protein structural information in solution. SAXS data can not only validate computational predictions, but can improve conformational and assembly prediction to produce atomic models that are consistent with solution data and biologically relevant states. Here, we describe how to obtain protein structure predictions, compare them …

Intracranial Mesenchymal Tumor, Fet::Creb Fusion-Positive In The Lateral Ventricle, Hanim I Ozkizilkaya, Jason M Johnson, Barbara J O'Brien, Ian E Mccutcheon, Sujit S Prabhu, Amol J Ghia, Gregory N Fuller, Jason T Huse, Leomar Y Ballester

Faculty, Staff and Student Publications

No abstract provided.

Clinical Insights Into Small Cell Lung Cancer: Tumor Heterogeneity, Diagnosis, Therapy, And Future Directions, Zsolt Megyesfalvi, Carl M Gay, Helmut Popper, Robert Pirker, Gyula Ostoros, Simon Heeke, Christian Lang, Konrad Hoetzenecker, Anna Schwendenwein, Kristiina Boettiger, Paul A Bunn, Ferenc Renyi-Vamos, Karin Schelch, Helmut Prosch, Lauren A Byers, Fred R Hirsch, Balazs Dome

Faculty, Staff and Student Publications

Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties. Genomic profiling of SCLC reveals genetic instability, almost universal inactivation of the tumor suppressor genes TP53 and RB1, and a high mutation burden. Because of early metastasis, only a small fraction of patients are amenable to curative-intent lung resection, and these individuals require adjuvant platinum-etoposide chemotherapy. Therefore, the vast majority of patients are currently being treated with chemoradiation with or …

Editorial: Non-Coding Genome And Endocrinology: From Bench To Bedside, Radu Pirlog, Kinga Nemeth, George Adrian Calin

Faculty, Staff and Student Publications

No abstract provided.

Lysosomal Tmem9-Lamtor4-Controlled Mtor Signaling Integrity Is Required For Mammary Tumorigenesis, Shengzhe Zhang, Sung Ho Lee, Litong Nie, Yuanjian Huang, Gengyi Zou, Youn-Sang Jung, Sohee Jun, Jie Zhang, Esther M Lien, Junjie Chen, Jae-Il Park

Faculty, Staff and Student Publications

No abstract provided.

The Mediating Effect Of Resilience On The Relationship Between Symptom Burden And Anxiety/Depression Among Chinese Patients With Primary Liver Cancer After Liver Resection, Xue Zhang, Haoran Zhang, Zonghao Zhang, Hua Fan, Shuwen Li

Faculty, Staff and Student Publications

Purpose: Primary liver cancer (PLC) is a common cancer of the digestive system. Patients with PLC often experience a heavy symptom burden and along with a significant levels of anxiety and depression after liver resection. High levels of symptom burden can lead to increased anxiety and depression, whereas high levels of resilience can alleviate these conditions. Therefore, we aimed to explore the relationships among symptom burden, resilience, and anxiety/depression in Chinese patients with PLC after liver resection and to determine whether resilience mediates the relationship between symptom burden and anxiety/depression.

Patients and methods: A total of 223 postoperative PLC patients …