Medicine and Health Sciences Commons^™

Instruction Program For Patients With Cholecystectomy Regarding Nutritional Knowledge, Haider Naiser Mousa, Huda Baqir Hassan

Al-Mustaqbal Journal of Pharmaceutical and Medical Sciences

The primary objective of this study is to assess the level of patients' understanding of the educational program following cholecystectomy. Additionally, the study attempts to determine the correlation between patients' knowledge and their socio-demographic factors. A quasi-experimental design study was conducted at AL Imam Sadiq Teaching Hospital. The study employed a non-probability selection method, namely selecting 30 patients for the study group and 30 patients for the control group. The instrument consists of 14 items. The validity of the questionnaire was assessed by a panel of 11 experts. The reliability of the questionnaire was determined by calculating the Alpha Correlation …

Preparation And Characterization Using A New Schiff Base Ligand Derived From Benzoyl Isothiocyanate With Their Complexes And Study Of Their Biological Activity, Zaynab Faleh Ai-Janahi, Mohammed Hamid Said

Al-Mustaqbal Journal of Pharmaceutical and Medical Sciences

Complexes containing Nickel, Copper, and Zinc salts were prepared and studied in this study. Additionally, novel Schiff Base ligands were synthesized by reacting 6-aminopenicillinic acid with benzoyl isothiocyanate to produce L. The synthesized ligand was evaluated by physical measures and spectroscopic methods such as Fourier transform infrared spectroscopy, nuclear magnetic resonance, ultraviolet-visible light, mass spectroscopy, and micro elemental analysis. Metal salts of (Ni(II), Cu(II), and Zn(II)) were combined with novel ligands at a molar ratio of 1:2 [M:L] to prepare the complexes. Spectroscopic, magnetic susceptibility, molar conductivity, atomic absorption, and DTA methods were used to study the complexes that were …

Diclofenac: A Review On Its Synthesis, Mechanism Of Action, Pharmacokinetics, Prospect And Environmental Impact, Hind A. Satar, Emad Yousif, Ahmed Ahmed

Al-Mustaqbal Journal of Pharmaceutical and Medical Sciences

Diclofenac, potent a nonsteroidal anti-inflammatory drug, used in the treatment of inflammation, pain and fever associated with a wide range of disease condition. This review article focuses the synthesis, mechanism of action, pharmacokinetics and derivatives of diclofenac and also highlights advances in the possible use of diclofenac in treating other condition outside its current clinical therapeutic use as an analgesic, anti-inflammatory and antipyretic agent as well the prospect of drug repurposing of diclofenac for treatment of disease like cancer. It further highlights the adverse effect of the drug as an emerging contaminant in the environment. Diclofenac acts by inhibition of …

Impact Of An Educational Program On Nurses' Knowledge Of Poisoning Management: A Quasi-Experimental Study, Ammar Ahmed Hatem, Tahseen Rajab Muhammad

Al-Mustaqbal Journal of Pharmaceutical and Medical Sciences

Background: Despite the critical role nurses play in managing poisoning cases, gaps in their knowledge can hinder patient outcomes. An educational program may address this deficit, but its effectiveness on nurses’ knowledge in poisoning management remains to be systematically evaluated.

Objectives:

This study aimed to examine the effect of an educational program on nurses’ knowledge of poisoning management.

Methods:

A quasi-experimental study with a pre- and post-test design was conducted on 80 nurses working in an emergency department (ED) in Al-Qādisiyyah Governorate, Iraq. The 80 nurses were randomly allocated into two groups of 40 to either receive the …

A Prospective, Multicenter Analysis Of The Integrated 31-Gene Expression Profile Test For Sentinel Lymph Node Biopsy (I31-Gep For Slnb) Test Demonstrates Reduced Number Of Unnecessary Slnbs In Patients With Cutaneous Melanoma., J Michael Guenther, Andrew Ward, Brian J Martin, Mark Cripe, Rohit Sharma, Stanley P Leong, Joseph I Clark, John Hamner, Timothy Beard

Oncology Articles

BACKGROUND: National Comprehensive Cancer Network guidelines recommend sentinel lymph node biopsy (SLNB) for patients with > 10% risk of positivity, consider SLNB with 5-10% risk, and foregoing with <  5% risk. The integrated 31-gene expression profile (i31-GEP) algorithm combines the 31-GEP with clinicopathologic variables, estimating SLN positivity risk.

METHODS: The i31-GEP SLNB risk prediction accuracy was assessed in patients with T1-T2 tumors enrolled in the prospective, multicenter DECIDE study (n = 322). To determine if incorporating the i31-GEP into decision-making resulted in fewer SLNBs performed, propensity score-matching was performed to a non-overlapping cohort for whom the 31-GEP was not used for SLNB decision-making.

RESULTS: No patients with <  5% i31-GEP predicted risk had a positive SLNB (0/35). Propensity matching demonstrated an 18.5% reduction in SLNBs performed (43.7% vs. 62.2%. p <  0.001). The i31-GEP could have reduced the number of unnecessary biopsies by 25.0% (35/140).

CONCLUSIONS: This prospective study confirmed the performance and clinical utility of the i31-GEP for …

Chronic Heavy Alcohol Intake And Liver-Specific Lrp-1 Reduction Increase Amyloidosis In Alzheimer’S Disease Mice, Devaraj V. Chandrashekar, G. Chuli Roules, Ross A. Steinberg, Urvashi R. Panchal, Nataraj Jagadeesan, Adenike Oyegbesan, Trinh Roselyn, Joshua Yang, Sharda R. Bhagwat, Hiya Rakholia, Rutvi D. Mevawala, Moom Roosan, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Chronic heavy alcohol drinking may be a modifiable risk factor for Alzheimer’s disease (AD), but studies in rodent AD models more closely mimic chronic moderate alcohol drinking in humans and largely focus on the brain. The role of the liver, which is significantly impacted by chronic heavy alcohol intake, in driving brain changes in alcohol-dependent AD remains unexplored. Our study using intragastric-ethanol feeding, which mimics chronic heavy alcohol intake in humans, in C57BL/6J mice showed significant AD-relevant changes in the brain and liver. Therefore, we aimed to investigate how hepatic changes using this model of chronic heavy drinking drive …

Multi Site Comparison Of Participant Profiles In The South Texas Alzheimer’S Disease Research Center, Jennifer G. Del Bosque, Chen-Pin Wang, Roman F. Fernandez, Jeremy A. Tanner, A. Campbell Sullivan, Sarah E. Savoia, Rosa V. Pirela, Silvia Mejia-Arango, Gladys Maestre, Sudha Seshadri

School of Medicine Publications

Background

Hispanic adults comprise 19% of the US population, yet 400% increase in ADRDs in this population is anticipated over the next twenty-five years. Knowledge is limited on the prevalence and influence of social determinants of health (SDoH) and modifiable risk factors on cognition in ethnically diverse groups. The South Texas Alzheimer’s Disease Research Center (STAC, P30AG066546) is a collaboration between UT Health San Antonio (UTHSA) and UT Rio Grande Valley (UTRGV) with a primary aim to better understand ADRDs in Hispanic adults. Our objective is (1) to describe differences in SDoH, modifiable risk factors, and cognitive performance in cognitively …

Mate-Pair Sequencing Enables Identification And Delineation Of Balanced And Unbalanced Structural Variants In Prenatal Cytogenomic Diagnostics, Jicheng Qian, Huilin Wang, Hailei Liang, Yuting Zheng, Mingyang Yu, Wing Ting Tse, Angel Hoi Wan Kwan, Lo Wong, Natalie Kwun Long Wong, Isabella Yi Man Wah, So Ling Lau, Shuk Yi Annie Hui, Matthew Hoi Kin Chau, Xiaoyan Chen, Rui Zhang, Liona C Poon, Tak Yeung Leung, Pengfei Liu, Kwong Wai Choy, Zirui Dong

Faculty, Staff and Students Publications

Background: Mate-pair sequencing detects both balanced and unbalanced structural variants (SVs) and simultaneously informs in relation to both genomic location and orientation of SVs for enhanced variant classification and clinical interpretation, while chromosomal microarray analysis (CMA) only reports deletion/duplication. Herein, we evaluated its diagnostic utility in a prospective back-to-back prenatal comparative study with CMA.

Methods: From October 2021 to September 2023, 426 fetuses with ultrasound anomalies were prospectively recruited for mate-pair sequencing and CMA in parallel for prenatal genetic diagnosis. Balanced/unbalanced SVs and regions with absence of heterozygosity (AOH) were detected and classified independently, and comparisons were made between mate-pair …

Genomic Data And Privacy, Candace T Myers, Runjun D Kumar, Lisa Pilgram, Luca Bonomi, Mara Thomas, Obi L Griffith, Stephanie M Fullerton, Richard A Gibbs

Faculty, Staff and Students Publications

No abstract provided.

Rethinking The Rise Of Early-Onset Gastrointestinal Cancers: A Call To Action, Benjamin A Weinberg, Caitlin C Murphy, David R Freyer, K Leigh Greathouse, Jan K Blancato, Elena M Stoffel, Julia L Drewes, Anne Blaes, John M Salsman, Y Nancy You, Hannah Arem, Reetu Mukherji, Priyanka Kanth, Xin Hu, Anne Fabrizio, Marion L Hartley, Marios Giannakis, John L Marshall

Faculty, Staff and Student Publications

Since the early 1990s, there has been a dramatic rise in gastrointestinal cancers diagnosed in patients under age 50 for reasons that remain poorly understood. The most significant change has been the increase in incidence rates of early-onset colorectal cancer, especially rates of left-sided colon and rectal cancers. Increases in gastric, pancreatic, and other gastrointestinal cancer diagnoses have further contributed to this trend. We formed a multidisciplinary Think Tank to develop a strategic, coordinated approach to studying early-onset gastrointestinal cancers. This area of research is challenging given multifactorial etiologies. We focused on epidemiology and the environment, the microbiome, and survivorship …

Assessing The Availability Of Adaptive Exercise For Adults With Ambulatory Disability, Erin Cullather, Lauren R. Hersh

Cooper Rowan Medical Journal

Background: Adults with an ambulatory disability are at higher risk of obesity and sequalae from obesity than aged-matched adults without disability. Research shows adults with an ambulatory disability are less likely to participate in the recommended 150 minutes of physical activity per week than non-disabledadults. Availability ofadaptive exercise could help increase physical activity participation in adults with ambulatory disability.

Objective: This observational study examines the availability of adaptive exercise programs throughout the United States and determines how it relates to the population of adults with an ambulatory disability.

Methods: Adaptive exercise sites (n=268) were identified via internet searches to form …

Detection Of Clinically Relevant Monogenic Copy-Number Variants By A Comprehensive Genome-Wide Microarray With Exonic Coverage, Matthew Hoi Kin Chau, Stephanie A Anderson, Rodger Song, Lance Cooper, Patricia A Ward, Bo Yuan, Chad Shaw, Paweł Stankiewicz, Sau Wai Cheung, Liesbeth Vossaert, Yue Wang, Nichole M Owen, Janice Smith, Carlos A Bacino, Katharina V Schulze, Weimin Bi

Faculty, Staff and Students Publications

Background: Disease-causing copy-number variants (CNVs) often encompass contiguous genes and can be detected using chromosomal microarray analysis (CMA). Conversely, CNVs affecting single disease-causing genes have historically been challenging to detect due to their small sizes.

Methods: A custom comprehensive CMA (Baylor College of Medicine - BCM v11.2) containing 400k probes and featuring exonic coverage for >4200 known or candidate disease-causing genes was utilized for the detection of CNVs at single-exon resolution. CMA results across a consecutive clinical cohort of more than 13 000 patients referred for genetic investigation at Baylor Genetics were examined. The genomic characteristics of CNVs impacting single …

Comprehensive Characterization Of The Transcriptional Landscape In Alzheimer’S Disease (Ad) Brains, Chengxuan Chen, Zhao Zhang, Yuan Liu, Wei Hong, Hande Karahan, Jun Wang, Wenbo Li, Lixia Diao, Meichen Yu, Andrew J Saykin, Kwangsik Nho, Jungsu Kim, Leng Han

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is the leading dementia among the elderly with complex origins. Despite extensive investigation into the AD-associated protein-coding genes, the involvement of noncoding RNAs (ncRNAs) and posttranscriptional modification (PTM) in AD pathogenesis remains unclear. Here, we comprehensively characterized the landscape of ncRNAs and PTM events in 1460 samples across six brain regions sourced from the Mount Sinai/JJ Peters VA Medical Center Brain Bank Study and Mayo cohorts, encompassing 33,321 long ncRNAs, 92,897 enhancer RNAs, 53,763 alternative polyadenylation events, and 900,221 A-to-I RNA editing events. We additionally identified 25,351 aberrantly expressed ncRNAs and altered PTM events associated with AD …

Its Own Architect: Flipping Cardiolipin Synthase, Katsuhiro Sawasato, William Dowhan, Mikhail Bogdanov

Faculty, Staff and Student Publications

Current dogma assumes that lipid asymmetry in biological membranes is actively maintained and dispensable for cell viability. The inner (cytoplasmic) membrane (IM) of Escherichia coli is asymmetric. However, the molecular mechanism that maintains this uneven distribution is unknown. We engineered a conditionally lethal phosphatidylethanolamine (PE)-deficient mutant in which the presence of cardiolipin (CL) on the periplasmic leaflet of the IM is essential for viability, revealing a mechanism that provides CL on the desired leaflet of the IM. CL synthase (ClsA) flips its catalytic cytoplasmic domain upon depletion of PE to supply nonbilayer-prone CL in the periplasmic leaflet of the IM …

Faecal Excretion Of Thorium By Norm Workers, Gregory S. Hewson, Martin Ralph, Marcus Cattani

Research outputs 2022 to 2026

Exposure to thorium-bearing dust in industries handling and processing monazite and other minerals can pose radiological risks to workers. This study aimed to reassess historical faecal bioassay data collected over 10 d from two monazite plant workers using updated biokinetic and dosimetric models. Another objective was to evaluate the feasibility of faecal thorium bioassay for contemporary operations involving naturally occurring radioactive materials (NORM). The retrospective analysis found that the bioassay-derived thorium intakes were significantly higher than those estimated via personal air sampling. The effective dose estimates for the two workers were similar and ranged from 0.95 to 2.40 mSv over …

A Propofol Binding Site In The Voltage Sensor Domain Mediates Inhibition Of Hcn1 Channel Activity, Verena Burtscher, Lei Wang, John Cowgill, Zi-Wei Chen, Christopher Edge, Edward Smith, Yongchang Chang, Lucie Delemotte, Alex S Evers, Baron Chanda

2020-Current year OA Pubs

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) ion channels are members of the cyclic nucleotide-binding family and are crucial for regulating cellular automaticity in many excitable cells. HCN channel activation contributes to pain perception, and propofol, a widely used anesthetic, acts as an analgesic by inhibiting the voltage-dependent activity of HCN channels. However, the molecular determinants of propofol action on HCN channels remain unknown. Here, we use a propofol-analog photoaffinity labeling reagent to identify propofol binding sites in the human HCN1 isoform. Mass spectrometry analyses combined with molecular dynamics simulations show that a binding pocket is formed by extracellularly facing residues in …

Rapid Viral Suppression Using Integrase Inhibitors During Acute Hiv-1 Infection, Mehri S Mckellar, Jessica R Keys, Lindsey M Filiatreau, Kara S Mcgee, Joann D Kuruc, Guido Ferrari, David M Margolis, Joseph J Eron, Charles B Hicks, Cynthia L Gay

2020-Current year OA Pubs

BACKGROUND: Antiretroviral therapy (ART) is recommended for all individuals with HIV infection, including those with acute HIV-1 infection (AHI). While recommendations are similar to those for chronic infection, efficacy data regarding treatment of acute HIV is limited.

METHODS: This was a single arm, 96-week study of a once-daily integrase inhibitor (INSTI)-based regimen using elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) in AHI. Primary endpoint was proportion of participants with HIV-1 RNA <200 copies/mL and <50 copies/mL by treatment weeks 24 and 48, respectively. We also examined time to viral suppression and weight gain after treatment initiation. Outcomes and characteristics were compared with a historical AHI cohort using a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF).

RESULTS: Thirty-three participants with AHI were enrolled with 31 available for analyses. Most were African American (61%) and men who have sex with men (73%). Median age was 26 (IQR 22-42). Demographics …

Pediatric Pulmonary Arterial Hypertension; Is It Possible To Predict Its Outcome?, Hala Mounir Agha, Ranya Hegazy, Ahmed Gamal, Ranya Essam, Antoine Abd Elmessih, Ahmed Behairy, Nagib Dahdah, Ahmed Abdelwahed, Nesrine Sobhy, Noha Ali

Journal of the Saudi Heart Association

Objectives: to assess the outcome of pediatric pulmonary arterial hypertension (PAH) and to identify the predictors of morbidity and mortality of this progressive disease. Patients and methods: This prospective observational cohort study was conducted on consecutive pediatric patients with PAH. Medical history was taken with a grading of the WHO functional class as well as the serum N-terminal pro-BNP (NT pro-BNP), six minutes’ walk test (6MWT), and echocardiography at the initial assessment and at follow-up. Results: The cohort study included 71 patients; 39 patients had idiopathic and heritable PAH, 27 patients had PH secondary to CHD and five patients had …

Are We Underestimating Exposures From Norm Dust?, Gregory S. Hewson, Martin Ian Ralph, Marcus Cattani

Research outputs 2022 to 2026

The inhalation of dust containing naturally occurring radioactive materials (NORM) associated with mining and mineral processing operations may lead to potential long-term health impacts, including cancer and chronic lung disease, due to alpha particle-emitting radionuclides. This study evaluates the effectiveness of air sampling strategies used to estimate radiation doses from NORM exposure, with a focus on the Western Australian minerals industry. The objectives were to review current sampling and analysis protocols, identify factors contributing to over- or underestimation of dose, and propose adjustments to improve intake assessments. A review of research and guidelines applicable to NORM dust exposure was conducted, …

The Postpartum Wellness Survey: Exploring The Role Of Social Determinants In The Diet–Depression Link, Ashley G. Brown

Department of Nutrition Student Projects

Postpartum mental health is a critical, yet both clinically and socially underrecognized, component of maternal care. Postpartum depression (PPD) affects up to 1 in 7 mothers and significantly impacts both maternal and family well-being. The Postpartum Wellness Survey (PWS) was developed to assess the interconnected relationships among dietary quality and nutrition knowledge, postpartum mood and emotional health, and social determinants of health (SDOH). Twenty-four participants within 12 months of delivery completed the survey, which integrated validated psychological and dietary assessment tools to capture community-level patterns in postpartum wellness. Composite scores across three PWS domains – Postpartum Mood and Emotional Health, …

Metabolism Of Co And H2 By Pioneer Bacteria In Volcanic Soils And The Phyllosphere, Nicola Fantom, Robin A. Dawson Phd, Rn, Cpnp-Pc, Edina Prondvai, Philippe Constant, Gary M. King, Hendrik Schäfer, Marcela Hernández

Publications

Trace gas degradation is a widespread metabolic adaptation in microbial communities, driving chemosynthesis and providing auxiliary energy that enhances persistence during nutrient starvation. In particular, carbon monoxide and hydrogen degradation can be of crucial importance for pioneering microbial communities colonising new, oligotrophic environmental niches, such as fresh volcanic deposits or the aerial interface of the phyllosphere. After volcanic eruptions, trace gas metabolism helps pioneer colonisers to initiate soil formation in ash deposits and on recently solidified lava, a vital ecosystem service. Similarly, in the phyllosphere, bacteria colonising newly emerging leaves and shoots, and/or persisting on the oligotrophic surface of plants, …

Pivotal Roles Of Biglycan And Decorin In Regulating Bone Mass, Water Retention, And Bone Toughness, Rui Hua, Yan Han, Qingwen Ni, Roberto J. Fajardo, Renato V. Iozzo, Rafay Ahmed, Jeffry S. Nyman, Xiaodu Wang, Jean X. Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Proteoglycans, key components of non-collagenous proteins in the bone matrix, attract water through their negatively charged glycosaminoglycan chains. Among these proteoglycans, biglycan (Bgn) and decorin (Dcn) are major subtypes, yet their distinct roles in bone remain largely elusive. In this study, we utilized single knockout (KO) mouse models and successfully generated double KO (dKO) models despite challenges with low yield. Bgn deficiency, but not Dcn deficiency, decreased trabecular bone mass, with more pronounced bone loss in dKO mice. Low-field nuclear magnetic resonance measurements showed a marked decrease in bound water among all KO groups, especially in Bgn KO and dKO …

Relationship Between Fluid Intake, Hydration Status And Cortisol Dynamics In Healthy, Young Adult Males, Mitchell E. Zaplatosch, Laurie Wideman, Jessica Mcneil, Jesse Sims, William M. Adams

Faculty Articles

Background: Previous studies have identified links between fluid intake, hydration related hormones and cortisol measured at one timepoint but have not considered how hydration may influence cortisol dynamics throughout the day. This study assessed associations between hydration status (copeptin, urinary osmolality, urine volume) and habitual fluid intake with cortisol dynamics.

Methods: The day before (DB) a 6-h laboratory visit, 29 male participants (age, 23±4y; BMI, 25.5 ± 4.3 kg/m2; body fat, 17.3 ± 9.3 %) provided 24-h urine samples and a fasted blood sample for hydration status assessment, recorded their 24-h fluid intake for three days prior, and provided 10 …

Novel Computational And Artificial Intelligence Models In Cancer Research, Li Liu, Fuhai Li, Xiaoming Liu, Kai Wang, Zhongming Zhao

Faculty, Staff and Student Publications

The ICIBM 2023 marked the 11th annual conference of its kind, with the ICIBM recently becoming the official conference of the International Association for Intelligent Biology and Medicine (IAIBM), showcasing cutting-edge advancements at the intersection of computation and biomedical research. A summary of the ICIBM 2023 program is provided by Li et al. [1]. As in previous years, cancer research remained a prominent focus, with numerous presentations highlighting innovative approaches to understanding and treating this complex disease. To summarize these contributions, selected works have been compiled in this Special Issue, “Novel Computational and Artificial Intelligence Models in Cancer …

Covid-19 Vaccine Hesitancy Among Black Women In The Us, Brittany C Slatton, Farrah G Cambrice, Serwaa S Omowale

Faculty, Staff and Student Publications

IMPORTANCE: COVID-19 vaccine hesitancy among Black women is a critical public health concern, potentially exacerbating existing health disparities and impacting community-wide vaccination efforts.

OBJECTIVE: To explore the factors associated with COVID-19 vaccine hesitancy among Black women in the US and identify the specific concerns and experiences shaping hesitant attitudes toward vaccination.

DESIGN, SETTING, AND PARTICIPANTS: Qualitative study using in-depth, semistructured interviews conducted virtually between June and November 2021. Thematic analysis was used to identify key themes from the interview data. Participants were recruited through social media platforms and word-of-mouth referrals from various regions of the US. Interviews were conducted remotely …

Nls-Binding Deficient Kapβ2 Reduces Neurotoxicity Via Selective Interaction With C9orf72-Als/Ftd Dipeptide Repeats, Kevin Kim, Amandeep Girdhar, Maria Elena Cicardi, V. Kankate, Miyuki Hayashi, Ruoyu Yang, Jenny Carey, Charlotte M Fare, James Shorter, Gino Cingolani, Davide Trotti, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Arginine-rich dipeptide repeat proteins (R-DPRs) are highly toxic proteins found in patients with C9orf72-linked amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). R-DPRs can cause toxicity by disrupting the natural phase behavior of RNA-binding proteins (RBPs). Mitigating this abnormal phase behavior is, therefore, crucial to reduce R-DPR-induced toxicity. Here, we use FUS as a model RBP to investigate the mechanism of R-DPR-induced aberrant RBP phase transition. We find that this phase transition can be mitigated by Kapβ2. However, as a nuclear import receptor and phase modifier for PY-NLS-containing RBPs, the function of WT Kapβ2 could lead to undesired interaction with its …

Enhanced Motivated Behavior Mediated By Pharmacological Targeting Of The Fgf14/Nav16 Complex In Nucleus Accumbens Neurons, Nolan M Dvorak, Paul A Wadsworth, Guillermo Aquino-Miranda, Pingyuan Wang, Douglas S Engelke, Jingheng Zhou, Nghi Nguyen, Aditya K Singh, Giuseppe Aceto, Zahra Haghighijoo, Isabella I Smith, Nana Goode, Mingxiang Zhou, Yosef Avchalumov, Evan P Troendle, Cynthia M Tapia, Haiying Chen, Reid T Powell, Timothy J Baumgartner, Jully Singh, Leandra Koff, Jessica Di Re, Ann E Wadsworth, Mate Marosi, Marc R Azar, Kristina Elias, Paul Lehmann, Yorkiris M Mármol Contreras, Poonam Shah, Hector Gutierrez, Thomas A Green, Martin B Ulmschneider, Marcello D'Ascenzo, Clifford Stephan, Guohong Cui, Fabricio H Do Monte, Jia Zhou, Fernanda Laezza

Faculty, Staff and Student Publications

Protein/protein interactions (PPI) play crucial roles in neuronal functions. Yet, their potential as drug targets for brain disorders remains underexplored. The fibroblast growth factor 14 (FGF14)/voltage-gated Na+ channel 1.6 (Nav1.6) complex regulates excitability of medium spiny neurons (MSN) of the nucleus accumbens (NAc), a central hub of reward circuitry that controls motivated behaviors. Here, we identified compound 1028 (IUPAC: ethyl 3-(2-(3-(hydroxymethyl)-1H-indol-1-yl)acetamido)benzoate), a brain-permeable small molecule that targets FGF14R117, a critical residue located within a druggable pocket at the FGF14/Nav1.6 PPI interface. We found that 1028 modulates FGF14/Nav1.6 complex assembly and depolarizes the voltage-dependence of Nav1.6 channel inactivation with …

Dexamethasone Dose Intensity Does Not Impact Outcomes In Newly Diagnosed Multiple Myeloma: A Secondary Swog Analysis, Rahul Banerjee, Rachael Sexton, Andrew J Cowan, Aaron S Rosenberg, Sikander Ailawadhi, S Vincent Rajkumar, Shaji Kumar, Angela Dispenzieri, Sagar Lonial, Brian G M Durie, Paul G Richardson, Saad Z Usmani, Antje Hoering, Robert Z Orlowski

Faculty, Staff and Student Publications

Dexamethasone is a key component of induction for newly diagnosed multiple myeloma (NDMM), despite common toxicities, including hyperglycemia and insomnia. In the randomized ECOG E4A03 trial, dexamethasone 40 mg once weekly was associated with lower mortality than higher doses. However, the performance of dexamethasone dose reductions below this threshold with regard to progression-free survival (PFS) and overall survival (OS) in NDMM has not been fully characterized. We conducted a secondary pooled analysis of the SWOG 0777 and SWOG 1211 studies of NDMM, which used lenalidomide and dexamethasone (Rd) alone, with or without bortezomib, and with or without elotuzumab. The planned …

Atrx Silences Cartpt Expression In Osteoblastic Cells During Skeletal Development, Yi-Ting Chen, Ming-Ming Jiang, Carolina Leynes, Mary Adeyeye, Camilla F Majano, Barakat Ibrahim, Urszula Polak, George Hung, Zixue Jin, Denise G Lanza, Lan Liao, Brian Dawson, Yuqing Chen-Evenson, Oscar E Ruiz, Richard J Gibbons, Jason D Heaney, Yangjin Bae, Brendan Lee

Faculty, Staff and Students Publications

ATP-dependent chromatin remodeling protein ATRX is an essential regulator involved in maintenance of DNA structure and chromatin state and regulation of gene expression during development. ATRX was originally identified as the monogenic cause of X-linked α-thalassemia mental retardation (ATR-X) syndrome. Affected individuals display a variety of developmental abnormalities and skeletal deformities. Studies from others investigated the role of ATRX in skeletal development by tissue-specific Atrx knockout. However, the impact of ATRX during early skeletal development has not been examined. Using preosteoblast-specific Atrx conditional knockout mice, we observed increased trabecular bone mass and decreased osteoclast number in bone. In vitro coculture …

Meta-Ea: A Gene-Specific Combination Of Available Computational Tools For Predicting Missense Variant Effects, Panagiotis Katsonis, Olivier Lichtarge

Faculty, Staff and Students Publications

Computational methods for estimating missense variant impact suffer from inconsistent performance across genes, which poses a major challenge for their reliable use in clinical practice. While ensemble scores leverage multiple prediction methods to enhance consistency, the overrepresentation of certain genes in the training data can bias their outcomes. To address this critical limitation, we propose a gene-specific ensemble framework trained on reference computational annotations rather than on clinical or experimental data. Accordingly, we generate Meta-EA ensemble scores that achieve comparable performance to the top individual predicting method for each gene set. Incorporating the effects of splicing and the allele frequency …