Medical Specialties Commons^™

Clinical Rarity: Simultaneous Choroid Plexus Papilloma And Extraventricular Neurocytoma Presenting As Intraventricular Hemorrhage In An Adolescent, Kaleb Derouen, Kierany Shelvin, Wesley Shoap, Randall Craver, Jerome Volk, Oritsejolomi A. Roberts

School of Medicine Faculty Publications

We present a patient with an intraventricular hemorrhage. Imaging identified a left atrial intraventricular mass and a vague adjacent second periventricular cystic lesion. A guided trans-sulcal approach via a left parietal craniotomy resulted in a gross total resection of both lesions. These represented two distinct lesions, the periventricular cystic lesion was an extraventricular neurocytoma (EVN) and a World Health Organization grade 1 choroid plexus papilloma (CPP). The neurocytoma required methylation studies for confirmatory diagnosis. The patient had an uneventful recovery with a normal neurological exam at 12-weeks. This documents the occurrence of two distinct central nervous system tumors, a CPP …

Associations Between Genetically Predicted Plasma Protein Levels And Alzheimer’S Disease Risk: A Study Using Genetic Prediction Models, Jingjing Zhu, Shuai Liu, Keenan A Walker, Hua Zhong, Dalia H Ghoneim, Zichen Zhang, Praveen Surendran, Sarah Fahle, Adam Butterworth, Md Ashad Alam, Hong-Wen Deng, Chong Wu, Lang Wu

Faculty, Staff and Student Publications

BACKGROUND: Specific peripheral proteins have been implicated to play an important role in the development of Alzheimer's disease (AD). However, the roles of additional novel protein biomarkers in AD etiology remains elusive. The availability of large-scale AD GWAS and plasma proteomic data provide the resources needed for the identification of causally relevant circulating proteins that may serve as risk factors for AD and potential therapeutic targets.

METHODS: We established and validated genetic prediction models for protein levels in plasma as instruments to investigate the associations between genetically predicted protein levels and AD risk. We studied 71,880 (proxy) cases and 383,378 …

Reactivation Of The G1 Enhancer Landscape Underlies Core Circuitry Addiction To Swi/Snf, Katerina Cermakova, Ling Tao, Milan Dejmek, Michal Sala, Matthew D Montierth, Yuen San Chan, Ivanshi Patel, Courtney Chambers, Mario Loeza Cabrera, Dane Hoffman, Ronald J Parchem, Wenyi Wang, Radim Nencka, Eveline Barbieri, H Courtney Hodges

Faculty, Staff and Student Publications

Several cancer core regulatory circuitries (CRCs) depend on the sustained generation of DNA accessibility by SWI/SNF chromatin remodelers. However, the window when SWI/SNF is acutely essential in these settings has not been identified. Here we used neuroblastoma (NB) cells to model and dissect the relationship between cell-cycle progression and SWI/SNF ATPase activity. We find that SWI/SNF inactivation impairs coordinated occupancy of non-pioneer CRC members at enhancers within 1 hour, rapidly breaking their autoregulation. By precisely timing inhibitor treatment following synchronization, we show that SWI/SNF is dispensable for survival in S and G2/M, but becomes acutely essential only during G1 phase. …

Development Of A Novel Covalently Bonded Conjugate Of Caprylic Acid Tripeptide (Isoleucine–Leucine–Aspartic Acid) For Wound-Compatible And Injectable Hydrogel To Accelerate Healing, Sachin B. Baravkar, Yan Lu, Abdul Razak Masoud, Qi Zhao, Jibao He, Song Hong

School of Medicine Faculty Publications

Third-degree burn injuries pose a significant health threat. Safer, easier-to-use, and more effective techniques are urgently needed for their treatment. We hypothesized that covalently bonded conjugates of fatty acids and tripeptides can form wound-compatible hydrogels that can accelerate healing. We first designed conjugated structures as fatty acid–aminoacid1–amonoacid2–aspartate amphiphiles (Cn acid–AA1–AA2–D), which were potentially capable of self-assembling into hydrogels according to the structure and properties of each moiety. We then generated 14 novel conjugates based on this design by using two Fmoc/tBu solid-phase peptide synthesis techniques; we verified their structures and purities through liquid chromatography with tandem mass spectrometry and nuclear …

Chlormethine Gel In Combination With Other Therapies For Treatment Of Mycosis Fungoides: A Review With Patient Cases, Marco Ardigò, Neda Nikbakht, Miriam Teoli, Laura Gleason, Liliana Crisan, Christiane Querfeld

Department of Dermatology and Cutaneous Biology Faculty Papers

Topical chlormethine gel has been approved as monotherapy for treatment of adult patients with mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma. In clinical practice, chlormethine gel is often combined with other skin-directed or systemic therapies to optimize response and target recalcitrant lesions. Positive outcomes with combination regimens using chlormethine gel and topical corticosteroids, phototherapy, retinoids, methotrexate, or interferon-α have been reported in literature. However, there are no treatment guidelines on the use of combination regimens with chlormethine gel. To provide real-world evidence and guidance on the use of chlormethine gel combination regimens, several cases of patients …

Exploiting The Carboxylate-Binding Pocket Of Β-Lactamase Enzymes Using A Focused Dna-Encoded Chemical Library, Suhyeorn Park, Jiayi Fan, Srinivas Chamakuri, Murugesan Palaniappan, Kiran Sharma, Xuan Qin, Jian Wang, Zhi Tan, Allison Judge, Liya Hu, Banumathi Sankaran, Feng Li, B V Venkataram Prasad, Martin M Matzuk, Timothy Palzkill

Faculty, Staff and Students Publications

β-Lactamase enzymes hydrolyze and thereby provide bacterial resistance to the important β-lactam class of antibiotics. The OXA-48 and NDM-1 β-lactamases cause resistance to the last-resort β-lactams, carbapenems, leading to a serious public health threat. Here, we utilized DNA-encoded chemical library (DECL) technology to discover novel β-lactamase inhibitors. We exploited the β-lactamase enzyme-substrate binding interactions and created a DECL targeting the carboxylate-binding pocket present in all β-lactamases. A library of 10

Chemical Catalysis Guides Structural Identification For The Major In Vivo Metabolite Of The Bet Inhibitor Jq1, Secondra Holmes, Prashi Jain, Kenneth Guzman Rodriguez, Jade Williams, Zhifeng Yu, Christian Cerda-Smith, Errol L G Samuel, James Campbell, John Michael Hakenjos, Diana Monsivais, Feng Li, Srinivas Chamakuri, Martin M Matzuk, Conrad Santini, Kevin R Mackenzie, Damian W Young

Faculty, Staff and Students Publications

The bromodomain inhibitor (+)-JQ1 is a highly validated chemical probe; however, it exhibits poor in vivo pharmacokinetics. To guide efforts toward improving its pharmacological properties, we identified the (+)-JQ1 primary metabolite using chemical catalysis methods. Treatment of (+)-JQ1 with tetrabutylammonium decatungstate under photochemical conditions resulted in selective formation of an aldehyde at the 2-position of the thiophene ring [(+)-JQ1-CHO], which was further reduced to the 2-hydroxymethyl analog [(+)-JQ1-OH]. Comparative LC/MS analysis of (+)-JQ1-OH to the product obtained from liver microsomes suggested (+)-JQ1-OH as the major metabolite of (+)-JQ1. The 2-thienyl position was then substituted to generate a trideuterated (−CD3, (+)-JQ1-D) …

Impact Of Genetic And Non-Genetic Factors On Phenotypic Diversity In Nbas-Associated Disease, Nicole Hammann, Dominic Lenz, Ivo Baric, Ellen Crushell, Carlo Dionisi Vici, Felix Distelmaier, Francois Feillet, Peter Freisinger, Maja Hempel, Anna L. Khoreva, Martin W. Laass, Yves Lacassie, Elke Lainka, Catherine Larson-Nath, Zhongdie Li, Patryk Lipiński, Eberhard Lurz, André Mégarbané, Susana Nobre, Giorgia Olivieri, Bianca Peters, Paolo Prontera, Lea D. Schlieben, Christine M. Seroogy, Cristina Sobacchi, Shigeru Suzuki, Christel Tran, Jerry Vockley

School of Medicine Faculty Publications

Biallelic pathogenic variants in neuroblastoma-amplified sequence (NBAS) cause a pleiotropic multisystem disorder. Three clinical subgroups have been defined correlating with the localisation of pathogenic variants in the NBAS gene; variants affecting the C-terminal region of NBAS result in SOPH syndrome (short stature, optic atrophy, Pelger-Huët anomaly), variants affecting the Sec 39 domain are associated with infantile liver failure syndrome type 2 (ILFS2) and variants affecting the ß-propeller domain give rise to a combined phenotype. However, there is still unexplained phenotypic diversity across the three subgroups, challenging the current concept of genotype-phenotype correlations in NBAS-associated disease. Therefore, besides examining the genetic …

Enhancing Mitosis Quantification And Detection In Meningiomas With Computational Digital Pathology, Hongyan Gu, Chunxu Yang, Issa Al-Kharouf, Shino Magaki, Nelli Lakis, Christopher Kazu Williams, Sallam Mohammad Alrosan, Ellie Kate Onstott, Wenzhong Yan, Negar Khanlou, Inma Cobos, Xinhai Robert Zhang, Neda Zarrin-Khameh, Harry V Vinters, Xiang Anthony Chen, Mohammad Haeri

Faculty, Staff and Student Publications

Mitosis is a critical criterion for meningioma grading. However, pathologists' assessment of mitoses is subject to significant inter-observer variation due to challenges in locating mitosis hotspots and accurately detecting mitotic figures. To address this issue, we leverage digital pathology and propose a computational strategy to enhance pathologists' mitosis assessment. The strategy has two components: (1) A depth-first search algorithm that quantifies the mathematically maximum mitotic count in 10 consecutive high-power fields, which can enhance the preciseness, especially in cases with borderline mitotic count. (2) Implementing a collaborative sphere to group a set of pathologists to detect mitoses under each high-power …

Multi-Site Benchmark Classification Of Major Depressive Disorder Using Machine Learning On Cortical And Subcortical Measures, Vladimir Belov, Tracy Erwin-Grabner, Moji Aghajani, Andre Aleman, Alyssa R Amod, Zeynep Basgoze, Francesco Benedetti, Bianca Besteher, Robin Bülow, Christopher R K Ching, Colm G Connolly, Kathryn Cullen, Christopher G Davey, Danai Dima, Annemiek Dols, Jennifer W Evans, Cynthia H Y Fu, Ali Saffet Gonul, Ian H Gotlib, Hans J Grabe, Nynke Groenewold, J Paul Hamilton, Ben J Harrison, Tiffany C Ho, Benson Mwangi, Natalia Jaworska, Neda Jahanshad, Bonnie Klimes-Dougan, Sheri-Michelle Koopowitz, Thomas Lancaster, Meng Li, David E J Linden, Frank P Macmaster, David M A Mehler, Elisa Melloni, Bryon A Mueller, Amar Ojha, Mardien L Oudega, Brenda W J H Penninx, Sara Poletti, Edith Pomarol-Clotet, Maria J Portella, Elena Pozzi, Liesbeth Reneman, Matthew D Sacchet, Philipp G Sämann, Anouk Schrantee, Kang Sim, Jair C Soares, Dan J Stein, Sophia I Thomopoulos, Aslihan Uyar-Demir, Nic J A Van Der Wee, Steven J A Van Der Werff, Henry Völzke, Sarah Whittle, Katharina Wittfeld, Margaret J Wright, Mon-Ju Wu, Tony T Yang, Carlos Zarate, Dick J Veltman, Lianne Schmaal, Paul M Thompson, Roberto Goya-Maldonado, Enigma Major Depressive Disorder Working Group

Faculty, Staff and Student Publications

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy …

Aging Fly Cell Atlas Identifies Exhaustive Aging Features At Cellular Resolution, Kenneth A Wilson, Sudipta Bar, Eric B Dammer, Enrique M Carrera, Brian A Hodge, Tyler A U Hilsabeck, Joanna Bons, George W Brownridge, Jennifer N Beck, Jacob Rose, Melia Granath-Panelo, Christopher S Nelson, Grace Qi, Akos A Gerencser, Jianfeng Lan, Alexandra Afenjar, Geetanjali Chawla, Rachel B Brem, Philippe M Campeau, Hugo J Bellen, Birgit Schilling, Nicholas T Seyfried, Lisa M Ellerby, Pankaj Kapahi

Faculty, Staff and Students Publications

Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd/OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids. Loss of mtd/OXR1 destabilized the retromer, causing improper protein trafficking and endolysosomal defects. Overexpression of retromer genes or pharmacological restabilization with R55 rescued lifespan and neurodegeneration in mtd-deficient flies and endolysosomal defects in fibroblasts from patients with lethal loss-of-function …

Covid-19 Convalescent Plasma Therapy Decreases Inflammatory Cytokines: A Randomized Controlled Trial, Feben Habtehyimer, Xianming Zhu, Andrew D Redd, Kelly A Gebo, Alison G Abraham, Eshan U Patel, Oliver Laeyendecker, Thomas J Gniadek, Reinaldo E Fernandez, Owen R Baker, Malathi Ram, Edward R Cachay, Judith S Currier, Yuriko Fukuta, Jonathan M Gerber, Sonya L Heath, Barry Meisenberg, Moises A Huaman, Adam C Levine, Aarthi Shenoy, Shweta Anjan, Janis E Blair, Daniel Cruser, Donald N Forthal, Laura L Hammitt, Seble Kassaye, Giselle S Mosnaim, Bela Patel, James H Paxton, Jay S Raval, Catherine G Sutcliffe, Matthew Abinante, Kevin S Oei, Valerie Cluzet, Marie Elena Cordisco, Benjamin Greenblatt, William Rausch, David Shade, Amy L Gawad, Sabra L Klein, Andrew Pekosz, Shmuel Shoham, Arturo Casadevall, Evan M Bloch, Daniel Hanley, Aaron A R Tobian, David J Sullivan

Faculty, Staff and Student Publications

This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.

Multiplex Immunofluorescence Captures Progressive Immune Exhaustion With Advancing Penile Squamous Cell Cancer Stage, Filip Ionescu, Jonathan Nguyen, Carlos Moran Segura, Mahati Paravathaneni, G Daniel Grass, Peter Johnstone, Niki M Zacharias, Curtis A Pettaway, Xin Lu, Youngchul Kim, Junmin Whiting, Jasreman Dhillon, Steven A Eschrich, Juskaran Chadha, Keerthi Gullapalli, Gabriel Roman Souza, Hiroko Miyagi, Brandon J Manley, Philippe E Spiess, Jad Chahoud

Faculty, Staff and Student Publications

Penile squamous cell carcinoma (PSCC) is a rare and deadly malignancy. Therapeutic advances have been stifled by a poor understanding of disease biology. Specifically, the immune microenvironment is an underexplored component in PSCC and the activity of immune checkpoint inhibitors observed in a subset of patients suggests immune escape may play an important role in tumorigenesis. Herein, we explored for the first time the immune microenvironment of 57 men with PSCC and how it varies with the presence of human papillomavirus (HPV) infection and across tumor stages using multiplex immunofluorescence of key immune cell markers. We observed an increase in …

Emerging Stroke Risk Factors: A Focus On Infectious And Environmental Determinants, Sajid Hameed, Nurose Karim, Mohammad Wasay, Narayanaswamy Venketasubramanian

Section of Neurology

This review focuses on emerging risk factors for stroke, including air pollution and climate change, gut microbiota, high altitude, and systemic infection. Up to 14% of all stroke-associated mortality is attributed to air pollution and is more pronounced in developing countries. Fine particulate matter and other air pollutants contribute to an increased stroke risk, and this risk appears to increase with higher levels and duration of exposure. Short term air pollution exposure has also been reported to increase the stroke risk. The gut microbiota is a complex ecosystem of bacteria and other microorganisms that reside in the digestive system and …

Sports-Related Concussion Management And Guideline Awareness In The Primary Care Setting, Stephanie K. Eble, Oleksandra Pashchenko, William Patterson, Christina T. Holt, William Dexter, Kristine Karlson

Journal of Maine Medical Center

No abstract provided.

Barriers To Care For Children With Cerebral Palsy In The Rural State Of Maine: A Mixed-Methods Study, Rayne L. Whitten, Anya K. Cutler, Alexa K. Craig

Journal of Maine Medical Center

Introduction: Guidelines on orthopedic hip surveillance in children with cerebral palsy have been published to minimize the effects of cerebral palsy and maximize quality of life. Researchers aimed to identify barriers to cerebral palsy care and to assess adherence to national hip-surveillance guidelines among a small subset of children with cerebral palsy who live in a rural state.

Methods: Parents of children with cerebral palsy were interviewed, and thematic analyses were performed on the recorded transcripts. Patient-specific data about imaging and demographics were manually extracted from the electronic health record to perform a mixed-methods analysis.

Results: Twenty-one parents were interviewed, …

Non-Ketotic Hyperglycemia Unmasks Hemichorea - A Reply, Ezhilkugan Ganessane, Sasikumar Mahalingam, Selva Ganesan

Journal of Community Hospital Internal Medicine Perspectives

No abstract for this article type

Autoimmune Hepatitis: An Unusual Presentation., Ahmed Ali Aziz, Muhammad Ali Aziz, Deep Mehta, Muhammad Humayoun Rashid

Journal of Community Hospital Internal Medicine Perspectives

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that occurs in a bimodal age distribution in the second and fifth-sixth decade of life. The disease is more prevalent in females and presents with variable clinical manifestations ranging from being asymptomatic to acute liver failure. AIH is often overlooked and not worked up in elderly patients who present with liver failure. This can lead to increased morbidity and mortality in elderly patients. AIH should be considered as a differential diagnosis in patients who present with elevated transaminases regardless of age or gender as early recognition and treatment leads to improved …

Cases From A Community Hospital…Jchimp Series #2: 66-Year-Old Man With Recurrent Painful Rashes And Oral Ulcerations, Fatima Halilu, Jing Wu, Joseph Fuscaldo, Nathan Dunsmore, Zain Syed, Pauline Daley

Journal of Community Hospital Internal Medicine Perspectives

This is part of a series of case reports detailing scenarios from our community hospital. The cases are selected to feature clinical dilemmas, provide a review on what is currently known about the topic with expert perspective. A 66-year-old black man presented to the primary care clinic with his fourth episode of generalized painful rash and oral ulcerations without a diagnosis despite two emergency room (ED) visits alongside doxycycline treatment. Symptoms interfered with daily activities with skin exam notable for widespread erythematous patches and plaques. In office biopsies were obtained with final diagnosis of erythema multiforme. Etiologic workup revealed positive …

Rare Case Of Mycobacterium Avium Complex Peritonitis In A Patient With Multiple Myeloma Undergoing Peritoneal Dialysis, Sacide S. Ozgur, Nida Ansari, Dhruv Patel, Ryan Rahman, Raymond Shih

Journal of Community Hospital Internal Medicine Perspectives

Mycobacterium avium complex (MAC) infections can present as a variety of severe diseases. While it has a predilection for immunocompromised patients such as those with Human immunodeficiency virus (HIV), it can also affect immunocompetent patients as well. One of the rare yet severe diseases that MAC infections can present is MAC peritonitis. Often hard to distinguish from other causes of peritonitis, high clinical suspicion should be maintained for those who are susceptible. Here we present an 85-year-old female with a past medical history of end-stage renal disease on peritoneal dialysis who presented with nausea and vomiting. She was found to …

De-Implementation Of Fecal Occult Blood Testing In The Emergency Department And Hospital Units: A Quality Improvement Project, Adewale Ajumobi, Joline De Castro, Ammar Qureshi

Journal of Community Hospital Internal Medicine Perspectives

Background: Fecal occult blood tests (FOBT) are inappropriately used in patients with melena, hematochezia, coffee ground emesis, iron deficiency anemia, and diarrhea. The use of FOBT for reasons other than screening for colorectal cancer is considered low-value and unnecessary. Methods: Quality Improvement Project that utilized education, Best Practice Advisory (BPA) and modification of order sets in the electronic health record (EHR). The interventions were done in a sequential order based on the Plan-Do-Study-Act (PDSA) method. An annotated run chart was used to analyze the collected data. Results: Education and Best Practice Advisory within the EHR led to significant reduction in …

Antibiotic-Induced Gut Dysbiosis Elicits Gut-Brain Axis Relevant Multi-Omic Signatures And Behavioral And Neuroendocrine Changes In A Nonhuman Primate Model, Shivdeep S. Hayer, Mackenzie Conrin, Jeffrey French, Andrew K. Benson, Sophie Alvarez, Kathryn Dempsey, Anne Fischer, Zahraa Wajih Alsafwani, William Gasper, Mallory J. Suhr Van Haute, Haley R. Hassenstab, Shayda Azadmanesh, Missy Briardy, Skyler Gerbers, Aliyah Jabenis, Jennifer L. Thompson, Jonathan B. Clayton

Food for Health: Publications

Emerging evidence indicates that antibiotic-induced dysbiosis can play an etiological role in the pathogenesis of neuropsychiatric disorders. However, most of this evidence comes from rodent models. The objective of this study was to evaluate if antibiotic-induced gut dysbiosis can elicit changes in gut metabolites and behavior indicative of gut-brain axis disruption in common marmosets (Callithrix jacchus) – a nonhuman primate model often used to study sociability and stress. We were able to successfully induce dysbiosis in marmosets using a custom antibiotic cocktail (vancomycin, enrofloxacin and neomycin) administered orally for 28 days. This gut dysbiosis altered gut metabolite profiles, …

Luminescence And Excited-State Reactivity In A Heteroleptic Tricyanido Fe(Iii) Complex, Yating Ye, Pablo Garrido-Barros, Joël Wellauer, Carlos M Cruz, Rodrigue Lescouëzec, Oliver S Wenger, Juan Manuel Herrera, Juan-Ramón Jiménez

Faculty, Staff and Student Publications

Harnessing sunlight via photosensitizing molecules is key for novel optical applications and solar-to-chemical energy conversion. Exploiting abundant metals such as iron is attractive but becomes challenging due to typically fast nonradiative relaxation processes. In this work, we report on the luminescence and excited-state reactivity of the heteroleptic [FeIII(pzTp)(CN)3]− complex (pzTp = tetrakis(pyrazolyl)borate), which incorporates a σ-donating trispyrazolyl chelate ligand and three monodentate σ-donating and π-accepting cyanide ligands. Contrary to the nonemissive [Fe(CN)6]3–, a broad emission band centered at 600 nm at room temperature has been recorded for the heteroleptic analogue attributed to the radiative deactivation from a 2LMCT excited state …

Outcomes Of Patients With Multiple Myeloma And 1q Gain/Amplification Receiving Autologous Hematopoietic Stem Cell Transplant: The Md Anderson Cancer Center Experience, Oren Pasvolsky, Sassine Ghanem, Denái R Milton, Mikael Rauf, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Yosra Aljawai, Hina N Khan, Partow Kebriaei, Hans C Lee, Krina K Patel, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

The prognostic impact of additional copies of chromosome 1q (1q + ) on outcomes of newly-diagnosed multiple myeloma (NDMM) patients undergoing autologous transplantation (autoSCT) is unclear. We conducted a retrospective single-center analysis of NDMM patients with 1q21 gain/amplification (3 or ≥4 copies of 1q, respectively) that received autoSCT between 2008-2018. 213 patients were included (79% 1q gain; 21% 1q amplification). The most commonly used induction regimen was bortezomib, lenalidomide, and dexamethasone (41%). At day100 post-autoSCT and at best post-transplant response, 78% and 87% of patients achieved ≥VGPR, and 38% and 50% achieved MRD-negative ≥VGPR, respectively. Median PFS and OS for …

The Effects Of Physical Activity On Experimental Models Of Vascular Dementia; A Systematic Review And Meta-Analysis, Ifechukwude J. Biose, Wesley H. Chastain, Rebecca J. Solch-Ottaiano, Viktoriya S. Grayson, Hanyun Wang, Somdeb Banerjee, Gregory J. Bix

School of Medicine Faculty Publications

Background; Physical activity is associated with improved brain health and cognition in humans. However, the validity, range, and quality of evidence for the beneficial outcomes linked to exercise in experimental models of vascular dementia (VaD) have not been evaluated. We performed a systematic review and meta-analysis of studies that assessed the effect of exercise intervention on models of VaD to provide an unbiased and comprehensive determination of the cognitive function and brain morphology benefits of exercise. Summary; A systematic search in three databases as well as study design characteristics and experimental data extraction were completed in December 2021. We investigated …

Regional Variability In The Prevalence Of Food Insecurity And Diet Quality Among United States Children, Jayna M Dave, Tzuan A Chen, Alexandra N Castro, Mamie White, Elizabeth A Onugha, Sloane Zimmerman, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Understanding the association between food security status (FSS) and diet quality in children is crucial. This study investigated regional variability in FSS, participation in the federal nutrition assistance program (FNAP), and diet quality among US children. National Health and Nutrition Examination Survey (NHANES) data from 2013 to 2016 were analyzed. The association between FSS, FNAP participation, and diet quality (Healthy Eating Index—HEI-2015) was assessed using multiple linear/logistic regression models. The sample included 6403 children (mean age: 7.5 years; 51% male; 33% Hispanic). Within the sample, 13% reported child food insecurity, and 30% reported household food insecurity. Additionally, 90% participated in …

Genome-Wide Study Investigating Effector Genes And Polygenic Prediction For Kidney Function In Persons With Ancestry From Africa And The Americas, Odessica Hughes, Amy R Bentley, Charles E Breeze, Francois Aguet, Xiaoguang Xu, Girish Nadkarni, Quan Sun, Bridget M Lin, Thomas Gilliland, Mariah C Meyer, Jiawen Du, Laura M Raffield, Holly Kramer, Robert W Morton, Mateus H Gouveia, Elizabeth G Atkinson, Adan Valladares-Salgado, Niels Wacher-Rodarte, Nicole D Dueker, Xiuqing Guo, Yang Hai, Adebowale Adeyemo, Lyle G Best, Jianwen Cai, Guanjie Chen, Michael Chong, Ayo Doumatey, James Eales, Mark O Goodarzi, Eli Ipp, Marguerite Ryan Irvin, Minzhi Jiang, Alana C Jones, Charles Kooperberg, Jose E Krieger, Ethan M Lange, Matthew B Lanktree, James P Lash, Paulo A Lotufo, Ruth J F Loos, Vy Thi Ha My, Jesús Peralta-Romero, Lihong Qi, Leslie J Raffel, Stephen S Rich, Erik J Rodriquez, Eduardo Tarazona-Santos, Kent D Taylor, Jason G Umans, Jia Wen, Bessie A Young, Zhi Yu, Ying Zhang, Yii-Der Ida Chen, Tanja Rundek, Jerome I Rotter, Miguel Cruz, Myriam Fornage, Maria Fernanda Lima-Costa, Alexandre C Pereira, Guillaume Paré, Pradeep Natarajan, Shelley A Cole, April P Carson, Leslie A Lange, Yun Li, Eliseo J Perez-Stable, Ron Do, Fadi J Charchar, Maciej Tomaszewski, Josyf C Mychaleckyj, Charles Rotimi, Andrew P Morris, Nora Franceschini

Faculty, Staff and Students Publications

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10−8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.

Development Of Right Ventricular Electromechanical Dyssynchrony Following Surgical Repair Of Tetralogy Of Fallot In Infants., Andrew W. Mccrary, Sydney D. Collins, Zebulon Z. Spector, P Andrea Kropf, Piers C A Barker, Joseph Kisslo, Daniel Forsha

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In adolescents and adults with tetralogy of Fallot (TOF), right ventricle (RV) electromechanical dyssynchrony (EMD) due to right bundle branch block (RBBB) is associated with reduced exercise capacity and RV dysfunction. While the development of RBBB following surgical repair of tetralogy of Fallot (rTOF) is a frequent sequela, it is not known whether EMD is present in every patient immediately following rTOF. The specific timing of the onset of RBBB following rTOF therefore provides an opportunity to assess whether acute RBBB is associated with the simultaneous acquisition of EMD.

METHODS: Transthoracic echocardiography with speckle tracking analysis for RV global …

Delineating The Mechanism Of Fragility At Bcl6 Breakpoint Region Associated With Translocations In Diffuse Large B Cell Lymphoma, Vidya Gopalakrishnan, Urbi Roy, Shikha Srivastava, Khyati M Kariya, Shivangi Sharma, Saniya M Javedakar, Bibha Choudhary, Sathees C Raghavan

Faculty, Staff and Student Publications

BCL6 translocation is one of the most common chromosomal translocations in cancer and results in its enhanced expression in germinal center B cells. It involves the fusion of BCL6 with any of its twenty-six Ig and non-Ig translocation partners associated with diffuse large B cell lymphoma (DLBCL). Despite being discovered long back, the mechanism of BCL6 fragility is largely unknown. Analysis of the translocation breakpoints in 5' UTR of BCL6 reveals the clustering of most of the breakpoints around a region termed Cluster II. In silico analysis of the breakpoint cluster sequence identified sequence motifs that could potentially fold into …

Molecular And Clinical Effects Of Aromatase Inhibitor Therapy On Skeletal Muscle Function In Early-Stage Breast Cancer, Tara A Seibert, Lei Shi, Sandra Althouse, Richard Hoffman, Bryan P Schneider, Kristen A Russ, Cody A Altherr, Stuart J Warden, Theresa A Guise, Andrew R Coggan, Tarah J Ballinger

Faculty, Staff and Student Publications

We evaluated biochemical changes in skeletal muscle of women with breast cancer initiating aromatase inhibitors (AI), including oxidation of ryanodine receptor RyR1 and loss of stabilizing protein calstabin1, and detailed measures of muscle function. Fifteen postmenopausal women with stage I-III breast cancer planning to initiate AI enrolled. Quadriceps muscle biopsy, dual-energy x-ray absorptiometry, isokinetic dynamometry, Short Physical Performance Battery, grip strength, 6-min walk, patient-reported outcomes, and serologic measures of bone turnover were assessed before and after 6 months of AI. Post-AI exposure, oxidation of RyR1 significantly increased (0.23 ± 0.37 vs. 0.88 ± 0.80, p <  0.001) and RyR1-bound calstabin1 significantly decreased (1.69 ± 1.53 vs. 0.74 ± 0.85, p <  0.001), consistent with dysfunctional calcium channels in skeletal muscle. Grip strength significantly decreased at 6 months. No significant differences were seen in isokinetic dynamometry measures of muscle contractility, fatigue resistance, or muscle recovery post-AI exposure. However, there was significant correlation between oxidation of RyR1 with muscle power (r = 0.60, p = 0.02) and muscle fatigue (r = 0.57, p = 0.03). Estrogen deprivation therapy for breast cancer resulted in maladaptive changes in skeletal muscle, consistent with the biochemical signature of dysfunctional RyR1 calcium channels. Future studies will evaluate longer trajectories of muscle function change and include other high bone turnover states, such as bone metastases.