Chemicals and Drugs Commons^™

A Comparison Of Microcrystal Electron Diffraction And X-Ray Powder Diffraction For The Structural Analysis Of Metal-Organic Frameworks, Erik Biehler, Silvana Pagola, Daniel Stam, Johannes Merkelbach, Christian Jandl, Tarek M. Abdel-Fattah

Chemistry & Biochemistry Faculty Publications

This study successfully implemented microcrystal electron diffraction (microED) and X-ray powder diffraction (XRPD) for the crystal structure determination of a new phase, TAF-CNU-1, Ni(C₈H₄O₄)·3H₂O, solved by microED from single microcrystals in the powder and refined at the kinematic and dynamic electron diffraction theory levels. This nickel metal–organic framework (MOF), together with its cobalt and manganese analogues with formula M (C₈H₄O₄)·2H₂O with M = Mn ^II or Co^II, were synthesized in aqueous media as one-pot preparations from the corresponding hydrated metal chlorides and sodium terephthalate, as a promising `green' synthetic route to moisture-stable MOFs. The crystal structures of the …

An E. Coli Two-Hybrid System To Investigate Human Protein-Protein Interactions, Rebecca M. Richardson, Sarah M. Ho, Lane Tong, Morgan G. Daniels, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Abstract

The LexA-E. coli two-hybrid (LexA-E2H) system was initially developed to study interactions between microbial proteins in an Escherichia coli (E. coli) environment. We here demonstrate its utility for studying mammalian protein interactions. Specifically, this study uses LexA-E2H to provide the first direct and quantitative validation of Glucose Regulated Protein 78 (GRP78) binding to the cleaved-Prostate Apoptosis Response 4 (cl-Par-4) tumor suppressor. Furthermore, the results establish that this interaction does not require phosphorylation of either protein. MacConkey agar was used for initial detection of the interaction through colorimetric colony screening, distinguishing pale white-pink colonies (+ interaction) from …

Deciphering The Chemistry Of Condensed Aromatic "Black" Carbon And Nitrogen In Amazonian Anthrosols, João Vitor Dos Santos, Aleksandar I. Goranov, Laís G. Fregolente, Marcia C. Bisinoti, Zhenhuan Sun, Klaus Schmidt-Rohr, Patrick G. Hatcher

Chemistry & Biochemistry Faculty Publications

Amazonian anthrosols are renowned for their high fertility and dark color, properties primarily attributed to the abundance of condensed aromatic carbon (ConAC) in the soil organic matter. ConAC, commonly referred to as black carbon, play a key role in the stability and nutrient retention of these soils. However, the processes governing the formation of ConAC and its transformation into oxygenated derivatives remain poorly understood. In this study, we used multiple analytical platforms to investigate the chemistry of ConAC-rich humic acids (HA) extracted from Terra Mulata de Indio, a type of Amazonian anthrosol. The results reveal that ConAC are predominantly …

Biomedical Mxene-Polymer Nanocomposites: Advancing Photothermal Therapy, Antibacterial Action, And Smart Drug Delivery: A Review, Ali Mohammad Amani, Lobat Tayebi, Ehsan Vafa, Mohammad Javad Azizli, Milad Abbasi, Ahmad Vaez, Hesam Kamyab, Daniel Simancas-Racines, Shreeshivadasan Chelliapan

Electrical & Computer Engineering Faculty Publications

MXenes are hydrophilic, conductive, tunable, and biocompatible two-dimensional ceramic materials prepared by etching the 'A' layer from their precursor MAX phases. Although MXenes show exceptional promise in photothermal therapy, biosensing, and regenerative medicine, they face challenges such as oxidative instability in physiological environments, limited drug-loading capacity, and unpredictable immune responses. To address these limitations, MXene/polymer nanocomposites incorporating both synthetic polymers (e.g., polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), and polylactic-co-glycolic acid (PLGA)) and natural biopolymers (e.g., cellulose nanofiber, gelatin, chitosan, hyaluronic acid, and soybean phospholipids) have been developed. These composites enhance functionality for biomedical applications such as photothermal cancer …

Molecular Imprinting And Nanomaterial Synergy For Lactate Detection, Christopher Animashaun, Gymama Slaughter

Center for Bioelectronics Publications

Molecularly imprinted polymer (MIP)-based electrochemical sensors have emerged as promising non-enzymatic platforms for the selective and stable detection of clinically and environmentally relevant biomarkers. This review provides a critical, comprehensive analysis of recent advances in MIP-based lactate sensing, with particular emphasis on hybrid systems that integrate conductive nanomaterials including gold and silver nanoparticles, laser-induced graphene, and reduced graphene oxide. These synergistic combinations leverage enhanced surface area, electrical conductivity, and molecular recognition to improve sensor sensitivity, selectivity, and long-term operational stability. Key fabrication strategies, such as electropolymerization, green nanomaterial synthesis, and surface imprinting, are critically examined for their roles in optimizing …

Optimization Of Serum And Salivary Cortisol Interpolation For Time-Dependent Modeling Frameworks In Healthy Adult Males, Nathaniel T. Berry, Travis Anderson, Christopher K. Rhea, Laurie Wideman

Rehabilitation Sciences Faculty Publications

Cortisol is an important marker of hypothalamic-pituitary-adrenal function and follows robust circadian and diurnal rhythms. However, biomarker sampling protocols can be labor-intensive and cost-prohibitive. Objectives: Explore analytical approaches that can handle differing biological sampling frequencies to maximize these data in more detailed and time-dependent analyses. Methods: Healthy adult males [N = 8; 26.1 (±3.1) years; 176.4 (±8.6) cm; 73.1 (±12.0) kg)] completed two 24 h admissions: one at rest and one including a high-intensity exercise session on the cycle ergometer. Serum and salivary cortisol were sampled every 60 and 120 min, respectively. Six alternative sampling profiles were defined by downsampling …

Neurotensin Regulates Primate Ovulation Via Multiple Neurotensin Receptors, Andrew C. Pearson, Jessica S. Miller, Hannah J. Jensen, Ketan Shrestha, Thomas E. Curry Jr., Diane M. Duffy

Department of Biomedical and Translational Sciences Faculty Publications

Neurotensin (NTS), a small neuropeptide, was recently established as a key paracrine mediator of ovulation. NTS mRNA is highly expressed by granulosa cells in response to the luteinizing hormone (LH) surge, and multiple NTS receptors are expressed by cells of the ovulatory follicle. To identify the role of NTS receptors NTSR1 and SORT1 in ovulation in vivo, the dominant follicle of cynomolgus macaques (Macaca fascicularis) was injected with either vehicle control, the general NTS receptor antagonist SR142948, the NTSR1-selective antagonist SR48692, or the SORT1-selective antagonist AF38469. Human chorionic gonadotropin (hCG) was then administered to initiate ovulatory events. …

Interaction Of Cardiac Leiomodin With The Native Cardiac Thin Filament, Madison Little, Cristina M. Risi, Tania M. Larrinaga, Mason D. Summers, Tyler Nguyen, Garry E. Smith Jr., Jennifer Atherton, Carol C. Gregorio, Alla S. Kostyukova, Vitold E. Galkin

Department of Biomedical and Translational Sciences Faculty Publications

Every heartbeat depends on cyclical contraction-relaxation produced by the interactions between myosin-containing thick and actin-based thin filaments (TFs) arranged into a crystalline-like lattice in the cardiac sarcomere. Therefore, the maintenance of thin filament length is crucial for myocardium function. The thin filament is comprised of an actin backbone, the regulatory troponin complex and tropomyosin that controls interactions between thick and thin filaments. Thin filament length is controlled by the tropomodulin family of proteins; tropomodulin caps pointed ends of thin filaments, and leiomodin (Lmod) promotes elongation of thin filaments by a “leaky-cap” mechanism. The broader distribution of Lmod on the thin …

The Central Role For Troponin C Amino-Terminal ⍺-Helix In Vertebrate Thin Filiment Ca²⁺-Activation, Yun Shi, Lauren A. Blackwell, Ryan K. Schroy, B. Max Cleland, Cristina M. Risi, Michelle S. Parvatiyar, Jose R. Pinto, Vitold E. Galkin, P. Bryant Chase

Department of Biomedical and Translational Sciences Faculty Publications

Troponin C (TnC) is the Ca²⁺-sensing subunit of troponin that is responsible for activating thin filaments in striated muscle, and, in turn, for regulating the systolic and diastolic contractile function of cardiac muscle. The secondary structure of vertebrate TnC is mainly composed of α-helices, with nine helices named sequentially, starting from the amino terminus, from N to A–H. The N-helix is a 12-residue-long α-helix located at the extreme amino terminus of the protein and is the only helical structure that does not participate in forming Ca²⁺-binding EF-hands. Evolutionarily, the N-helix is found only in TnC from mammalian species and most …

Deletion Of Chop In Beta Cell Protects Mice From Cardiovascular Complications In Type 2 Diabetes: Evidence From A Pre-Clinical Mouse Model, Balaji Srinivas, Kiran Alluri, Nour-Eddine Rhaleb, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Introduction

Cardiovascular complications are the leading cause of morbidity and mortality in patients with type 2 diabetes (T2D), which is recognized as a major independent risk factor for coronary artery disease, stroke, peripheral vascular disease, and heart failure. The interrelationship between metabolic dysfunction and cardiovascular disease is complex and multifactorial, involving hyperglycemia, insulin resistance, inflammation, and oxidative stress. Evidence indicates that endoplasmic reticulum (ER) stress and induction of the unfolded protein response (UPR) contribute to metabolic dysregulation and vascular dysfunction. However, the specific role of beta cell-derived UPR mediators, particularly C/EBP homologous protein (CHOP), in coordinating this interorgan axis between …

Reduced Slow Wave Sleep Is Associated With Increased Risk Of Short Stature In Children: A Cross-Sectional Study, Zhaohua Chen, Yuan Shi, Fei Lei, Xujun Feng, Lu Tan, Taomei Li, Junying Zhou, Yuanfeng Sun, Jiamin Liao, Yun Li, Zhoulong Yu, Jian Jiao, Yanyan Wang, Larry D. Sanford, Michael V. Vitiello, Ye Zhang, Rong Ren, Xiangdong Tang

Department of Biomedical and Translational Sciences Faculty Publications

Objective: Although growth hormone was shown to be specifically released during slow wave sleep (SWS), no population-based evidence has demonstrated the association between sleep quality and childhood height. To address this gap, our study aims to investigate the relationship between SWS and height of children.

Methods: We analyzed polysomnography data and z-scores for height in 2527 suspected obstructive sleep apnea (OSA) children (537 non-OSA children and 1990 OSA children) collected over the past 16 years. Different grades of z-scores for height and SWS were classified by the quartile method, and the lowest z-scores for height quartile defined short stature as …

Phenotype Specific Nuclear Lamina Remodeling In Hipsc Derived Cardiomyocytes Bearing Tnnt2 Sarcomeric Variants, Isabella Leite Coscarella, Olalekan H. Usman, Lili Wang, Maicon Landim-Vieira, Lillian Wirstiuk, Amber N. Brown, Diego A. R. Zorio, Brian K. Washburn, Cynthia Vied, Bjorn C. Knollmann, Christopher Solís, Vitold E. Galkin, P. Bryant Chase, J. Travis Hinson, Jerome Irianto, Jose Renato Pinto

Department of Biomedical and Translational Sciences Faculty Publications

[Summary] Cardiomyocytes endure physical stress from the myocardium environment while generating their own mechanical strains. The force generated by sarcomeres is transmitted both longitudinally to adjacent sarcomeres and laterally to the cytoskeleton via intermediate filaments. This mechanical stimulus impacts other organelles, including the nucleus, thus playing a vital role in sensing and signaling nuclear adaptations. However, there is limited understanding of how changes in cardiac contractility affect nuclear mechanics. Here, we sought to investigate the effects of hyper- and hypo-contractility in nuclei of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) bearing TNNT2 pathogenic variants associated with hypertrophic (HCM) or dilated …

Enhancing Bone Regeneration Using Kaempferol As An Osteoprotective Compound: Signaling Mechanisms, Delivery Strategies, And Potential Applications, Mojdeh Salehi Namini, Sanam Mohandesnezhad, Sadaf Mohandesnezhad, Vahid Mansouri, Lobat Tayebi, Nima Beheshtizadeh

Electrical & Computer Engineering Faculty Publications

Various plants, including fruits, vegetables, and spices, contain kaempferol, a bioflavonoid compound with diverse medicinal effects, such as antioxidant, antibacterial, and anti-inflammatory characteristics. Furthermore, this compound exhibits multiple health-promoting properties, including osteoprotection and osteogenesis, primarily by modulating various cell-signaling pathways. This review aims to illustrate the medical advantages of kaempferol and its role in regulating bone metabolism through cell signaling mechanisms. Numerous studies have demonstrated the bone-protective properties of kaempferol and its encapsulated form. Further research is needed to clarify the optimal dosages, toxicity, safety, and other potential mechanisms of action. This review demonstrates that several signaling pathways, including nuclear …

Opioid Usage And Non-Opioid Alternatives In Septorhinoplasty: A Narrative Review, Robert M. Frederick, Eric Dobratz

Department of Otolaryngology (ENT) Faculty Publications

Background and Objective: Opioids are routinely prescribed following septorhinoplasty and oftentimes surgeons prescribe a larger number of tablets than patients require. Considering the high risk of developing opioid dependence and risk of diversion, it is imperative that surgeons practice safer, evidence-based prescribing habits. This review is intended to detail the current state of opioid usage after septorhinoplasty, focusing on articles that show pertinent and practice-altering findings. This will allow surgeons to reflect on their prescribing patterns and make evidence-based decisions to improve them.

Methods: A literature search was performed in November 20, 2024 via PubMed using keywords such as ‘opioid …

Acute Exacerbations Of Chronic Rhinosinusitis, Robert M. Frederick, Kent Lam, Joseph K. Han

Department of Otolaryngology (ENT) Faculty Publications

Purpose of Review

We aim to highlight recent advancements on the evolving chronic rhinosinusitis (CRS) phenotype: acute exacerbations of chronic rhinosinusitis (AECRS). We focused on studies that expanded the current understanding of its pathophysiology, patient characteristics, and disease burden.

Recent findings

Defining AECRS has been a topic of discussion for many years. A recent regulatory definition of AECRS in the literature incorporates a > 3 day requirement of worsened symptoms and an escalation of treatment. It is important not to rely on patient-reported rescue medication frequency as it was recently demonstrated these are only obtained for 1/3 of reported AECRS episodes. …

Caveolin-Mediated Endocytosis: Bacterial Pathogen Exploitation And Host-Pathogen Interaction, Dibyasri Barman, Rishi Drolia

Biological Sciences Faculty Publications

Within mammalian cells, diverse endocytic mechanisms, including phagocytosis, pinocytosis, and receptor-mediated endocytosis, serve as gateways exploited by many bacterial pathogens and toxins. Among these, caveolae-mediated endocytosis is characterized by lipid-rich caveolae and dimeric caveolin proteins. Caveolae are specialized microdomains on cell surfaces that impact cell signaling. Caveolin proteins facilitate the creation of caveolae and have three members in vertebrates: caveolin-1, caveolin-2, and caveolin-3. Many bacterial pathogens hijack caveolin machinery to invade host cells. For example, the Gram-positive facultative model intracellular bacterial pathogen Listeria monocytogenes exploits caveolin-mediated endocytosis for efficient cellular entry, translocation across the intestinal barrier, and cell–cell spread. Caveolin …

Irritable Bowel Syndrome Risk In Acne Patients: Implications For Dermatologic Care, Alex Y. Liu, Ana Ormaza Vera, Clinton W. Enos

Department Dermatology Faculty Publications

[Practice points]

• Clinicians should consider monitoring for early signs of irritable bowel syndrome (IBS) in adult patients with acne to facilitate prompt diagnosis and intervention.
• Clinicians should remain judicious when prescribing antibiotics for acne management to minimize potential disruptions to the gut microbiota and the risk for IBS.
• Isotretinoin may serve as a safer alternative to antibiotics in patients with acne, particularly those with gastrointestinal concerns.

A Novel D-Peptide Modulates Dclk1 Gelsolin Interactions, Reducing Pdac Tumor Growth, Landon L. Moore, Dongfeng Qu, Parthasarathy Chandrekesan, Kamille Pitts, Randal May, Byron E. Anderson, Milton L. Brown, Courtney W. Houchen

Department of Medicine Faculty Publications

What drives inflammation-associated tumorigenesis and progression in pancreatic ductal adenocarcinoma (PDAC)? Doublecortin-like kinase 1 (DCLK1) is a central driver of inflammation-associated tumorigenesis, with elevated expression linked to worse clinical outcomes. Two isoforms of DCLK1 possess a unique extracellular domain (ECD). DCLK1 isoform 2 contains two microtubule-binding domains, while isoform 4, lacks the microtubule-binding domains but, plays a pivotal role in tumor progression. We identified novel D-peptides that selectively target this ECD, significantly suppressing PDAC cell proliferation in vitro and tumor growth in xenograft models without inducing cell death. In silico modeling and binding assays revealed DCLK1 isoform 4 interacts with …

Discordance Between Profound Hyperprolactinemia And Hormone Immunostaining In A Pit1-Positive Pituitary Neuroendocrine Tumor. A Rare Case Report, Aneela Arif, Radwa Osman

Department of Medicine Faculty Publications

We present a rare case of a functioning macroprolactinoma with negative hormone immunohistochemistry (IHC) but positive PIT1 transcription factor staining. This case highlights the diagnostic value of transcription factor IHC when clinical and biochemical findings are discordant with hormone staining. An 18-year-old female with unremarkable medical history presented with high prolactin levels, galactorrhea, and amenorrhea for 6 months. She was not on any medications, and was not sexually active, or trying to conceive. Prolactin levels were markedly elevated (462, 1,067, and 1,282 ng/mL). MRI showed a 13×12×14 mm T2-hyperintense, slightly cystic pituitary macroadenoma with suprasellar extension and optic chiasm compression, …

Fibrinolysis For Apical Thrombus As A Bridge To Emergent Valve-In-Valve Transcatheter Aortic Valve Replacement, Nicholas J. Valle, Omar A. Saleh, Mani C. Akunuri, Parth K. Parikh, Joshua A. Cohen, Deepak R. Talreja, Matthew R. Summers

Department of Medicine Faculty Publications

Background

Left ventricular (LV) thrombus is traditionally a contraindication to transcatheter aortic valve replacement due to embolic risk. Consequently, management of valvular cardiogenic shock complicated by LV thrombus identifies unique challenges that require innovative strategies.

Case Summary

A 58-year-old woman with critical bioprosthetic aortic stenosis, cardiogenic shock, and large LV thrombus (2.8 × 2.6 cm) underwent successful valve-in-valve transcatheter aortic valve replacement after systemic fibrinolysis bridge therapy.

Why Beyond the Guidelines

Current guidelines contraindicate transcatheter aortic valve replacement in patients with LV thrombus. This case demonstrates the novel use of low-dose, slow infusion tissue plasminogen activator as a bridge therapy …

Diverticulitis—New Evidence To Share With Patients, Nicholas B. D'Alessandro, Tarun Vippa, Edward C. Oldfield Iv, David A. Johnson

Department of Medicine Faculty Publications

Diverticulitis is one of the most common gastrointestinal causes of hospitalization in Western society. While previously characterized as a disease of older patients, new literature highlights an increasing incidence among the younger population. Over the past few decades, the understanding of etiology and management of diverticulitis has changed drastically. New data refute past beliefs while promoting other novel recommendations to mitigate incidence and subsequent complications. Data now confirms the safety and possible protective benefit of particulate food, while highlighting evidence-based approaches for the use of diagnostic imaging and antibiotics. We recognize modifiable and non-modifiable risk factors that are commonly seen …

Exploring Differences In Cannabis Use And Harm Perceptions Among Sexual Minority And Heterosexual Females: A Brief Report, Sarah J. Ehlke, Samantha A. Fitzer, Kendra Rigney

Psychology Faculty Publications

Objective: Sexual minority women (SMW) have higher rates of cannabis use compared to heterosexual women, which may be partially attributed to lower harm perceptions. However, no study has examined if the association between harm perceptions and cannabis use is stronger for SMW than heterosexual women. This study examined if sexual identity (SMW vs. heterosexual woman) moderated the association between harm perceptions and past 30-day cannabis use among a sample of female young adults (18-25 years old). Method: Participants were 949 (29.8% SMW; Mean age = 24.33; 92.1% non-Hispanic White) females (99.3% cisgender) recruited from Amazon Mechanical Turk who reported weekly …

Willingness To Use Long-Acting Injectable Pre-Exposure Prophylaxis (Lai-Prep) Among Black Cisgender Women In The Southern United States, Sylvia Shangani, Jaquetta M. Reeves, Kristin Heron, Jessica M. Sales, Kenneth K. Mugwanya

Psychology Faculty Publications

Background

Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) for HIV prevention may improve adherence for those with concerns with daily pills. Limited data exist on LAI-PrEP acceptability among Black women in the U.S., a population vulnerable to HIV. We assessed willingness to use LAI-PrEP among Black women eligible for PrEP in the Southern U.S.

Methods

We conducted a cross-sectional online survey of HIV-negative Black women from March to June 2022 in the U.S. South. Participants provided information on sociodemographic characteristics, HIV knowledge, PrEP awareness, and use, stigma, risk perception, medical mistrust, and healthcare access. Multivariate logistic regression models determined factors associated with …

Formulation Development Of Dual-Compartment Topical Inserts Combining Tenofovir Alafenamide And Elvitegravir For Flexible On-Demand Hiv Prevention, Vivek Agrahari, M. Melissa Peet, Neelima Chandra, Prakash Ramalingam, Pardeep K. Gupta, Sriramakamal Jonnalagadda, Onkar N. Singh, Timothy J. Mccormick, Gustavo F. Doncel, Meredith R. Clark

Department of Obstetrics & Gynecology Faculty Publications

Pre-exposure prophylaxis (PrEP) has emerged as a prominent approach for the prevention of HIV infections. While the latest advances have resulted in effective oral and injectable product options, there are still gaps in on-demand, event-driven, topical products for HIV prevention that are safe and effective. Here we describe the formulation development of a dual-compartment topical insert containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) that may be administered when needed, vaginally or rectally, pre- or post-coitus, for flexible HIV prophylaxis. Specifically, we describe the lab-scale formulation development, preclinical mucosal safety and pharmacokinetics (PK) testing in rabbits, long-term stability, and scale-up …

Mobile Health Intervention Tools Promoting Hiv Pre-Exposure Prophylaxis Among Adolescent Girls And Young Women In Sub-Saharan Africa: Scoping Review, Alex Emilio Fischer, Homaira Hanif, Jacob B. Stocks, Aimee E. Rochelle, Karen Dominguez, Eliana Gabriela Armora Langoni, H. Luz Mcnaughton Reyes, Gustavo F. Doncel, Kathryn E. Muessig

Department of Obstetrics & Gynecology Faculty Publications

Background:

In 2022, 3100 adolescent girls and young women in sub-Saharan Africa experienced new HIV infections each week. HIV pre-exposure prophylaxis (PrEP) is effective at preventing HIV but has limited uptake and persistence. Mobile health (mHealth) interventions can improve medication adherence; however, their utility to improve PrEP adherence among adolescent girls and young women is not well established.

Objective:

This scoping review synthesizes evidence supporting mHealth for PrEP among adolescent girls and young women in sub-Saharan Africa and identifies strategies for further evaluation.

Methods:

We searched PubMed and Google Scholar databases, expert referrals, and reference lists using the following eligibility …

American Heart Association Blood Pressure Classification And Subsequent Risk Of Preeclampsia, Rebecca Horgan, Erkan Kalafat, Elena Sinkovskaya, Alfred Abuhamad, George Saade

Department of Obstetrics & Gynecology Faculty Publications

Background: In 2017, the American Heart Association (AHA) and American College of Cardiology updated their hypertension guidelines for the nonpregnant population, lowering the diagnostic thresholds to systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg. This reclassification has raised important questions regarding whether blood pressure (BP) values previously considered within the normal range in pregnancy may, in fact, confer an increased risk for hypertensive disorders of pregnancy (HDPs).

Objective: To evaluate the association between first-trimester BP classified by AHA thresholds and the subsequent development of HDPs.

Study design: This was a secondary analysis of a prospective, multicenter cohort …

Her2 Alterations Across Solid Tumors: Implications For Comprehensive Testing, Ahmed Ismail, Chimay Jani, Nusrat Jahan, Malla Midhun, Arnab Basu, Garima Gupta, Bassel El-Rayes, Sejong Bae, Tyler Mattox, Cyntanna Hawkins, Rebecca C. Arend, Mehmet Akce, Yanis Boumber, Aakash Desai

Department of Medicine Faculty Publications

Purpose

ERBB2 (HER2) alterations (e.g., overexpression, amplification, and mutations) are known to drive tumor progression. These changes, particularly in non-breast and gastric/gastroesophageal cancers, remain poorly characterized. With pan-tumor approval of HER2-targeted therapies like Trastuzumab deruxetecan (T-DXd), understanding ERBB2 alterations across diverse cancers is crucial.

Methods

HER2 analysis was conducted on 653 solid tumor specimens at the University of Alabama, using immunohistochemistry (IHC), copy number (CN) variation (CNV) assessment, and mutational profiling. The correlation between CN amplification and IHC expression was evaluated using Somers' D ordinal association.

Results

Of the 653 cases, HER2 IHC scores were distributed as 3 + (3.1%), …

Changes In Cardiovascular Risk Factors And Health Care Expenditures Among Patients Prescribed Semaglutide, Yuan Lu, Yuntian Lu, Tedi Totojani, Chungsoo Kim, Rohan Khera, Hua Xu, John E. Brush Jr., Harlan M. Krumholtz, Jason Abaluck

Department of Medicine Faculty Publications

Importance Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated substantial weight reduction and cardiovascular benefits in clinical trials. However, its association with clinical outcomes and health care expenditures remains underexplored.

Objective To evaluate changes in cardiovascular risk factors and health care expenditures among patients prescribed semaglutide across multicenter cohorts.

Design, Setting, and Participants This retrospective cohort study included 23 522 adults (≥18 years) who received an initial semaglutide prescription between January 1, 2018, and January 1, 2025, at Sentara Healthcare and between January 1, 2018, and May 1, 2025, at Yale New Haven Health System.

Exposure The first prescription of …

Psychedelic Minimalism: The Case Against Music In Psychedelic Therapy Settings, Samir A. Nader

Department of Medicine Faculty Publications

[Introduction: reframing the role of setting] In recent years, renewed attention has been given to the centrality of set and setting in psychedelic-assisted therapy. The Reporting of Setting in Psychedelic Clinical Trials (ReSPCT) guidelines reflect an evolving consensus: therapeutic outcomes are not solely pharmacologically determined but are heavily shaped by both the environment and the psychological state of the participant (2). Within this evolving paradigm, music has assumed a privileged role, framed as a therapeutic constant, typically curated to be emotionally supportive or evocative, and especially emphasized during peak psychedelic states (3). The prevailing assumption is that music facilitates safety, …

Inflammatory Mediators And The Rage Pathway In Placental Tissues Of Pregnancies Complicated By Severe Preeclampsia, Neelima Chandra, Thomas D. Kimble, Kathleen R. Heim, Sharon M. Anderson, Andrew P. Wong, Andrea R. Thurman, Gustavo F. Doncel

CONRAD Publications

Introduction: Preeclampsia (PE) is a complex multisystem disorder of pregnancy associated with abnormal placentation, vascular anomalies, and systemic inflammation and hypertension. Previous research assessing inflammatory triggers of the condition used plasma, amniotic fluid, or explant samples. Studies using placental tissue from either vaginal or cesarean deliveries are confined to semiquantitative analysis using subjective scoring methods and generally involve a small sample size.

Methods: In this study, we have quantified the expression of inflammatory mediators by immunohistochemical image analysis of archived placental tissues obtained from cesarean delivery of preeclamptic, chorioamnionitic, and normal pregnancies.

Results: Among the inflammatory mediators, we found a …