Medicine and Health Sciences Commons^™

Tng260 Is A Small-Molecule Corest Inhibitor That Sensitizes Stk11-Mutant Tumors To Anti-Pd-1 Immunotherapy, Leanne G Ahronian, Soumyadip Sahu, Minjie Zhang, Ayushi S Patel, Ke Geng, Reshmee Bhattacharya, Gerald S Falchook, Jonathan W Goldman, Alexander I Spira, Salman R Punekar, David R Spigel, Judy S Wang, Ferdinandos Skoulidis, Janaye Stephens, Mary Meynardie, Jaylen M Powell, Alfonso Lopez, Michela Ranieri, Magdalena A Ploszaj, Yi Jer Tan, Yeuan Ting Lee, Yi Yu, Jiehui Deng, Ting Chen, Patrick Mccarren, Alice Tsai, Suleman S Hussain, Brian Doyon, Kenjie Amemiya, Jacques Ermolieff, Preksha Shahagadkar, Nikitha M Das, Lauren R Flynn, Julie A Shields, Laney Danielczyk, Brian J Mcmillan, Andre Mignault, Samuel R Meier, Hsin-Jung Wu, David J Guerin, Douglas A Whittington, Chengyin Min, Iga Sienczylo, John P Maxwell, Heather J Dibenedetto, Hideo Watanabe, Brian B Haines, Alan Huang, Adam Crystal, Jannik N Andersen, Xinyuan Wu, Kwok-Kin Wong

Faculty, Staff and Student Publications

Patients with non–small cell lung cancer (NSCLC) with loss of the tumor suppressor gene STK11 are resistant to immune checkpoint therapies like anti–PD-1. In this study, we conducted an in vivo CRISPR screen that identified histone deacetylase 1 as a target to reverse anti–PD-1 resistance driven by loss of STK11 and developed TNG260, a potent small-molecule inhibitor of the CoREST complex with selectivity exceeding previously generated inhibitors in this class in preclinical studies. Treatment with TNG260 led to increased expression of immunomodulatory genes in STK11-deficient cancer cells. When combined with anti–PD-1, TNG260 induced immune-mediated stasis and/or regression in STK11 …

Preoperative Brain Mapping Predicts Language Outcomes After Eloquent Tumor Resection, Matthew T Muir, Kyle Noll, Sarah Prinsloo, Hayley Michener, Jeffrey I Traylor, Vinodh A Kumar, Chibawanye I Ene, Sherise Ferguson, Ho-Ling Liu, Jeffrey S Weinberg, Frederick Lang, Brian A Taylor, Stephanie J Forkel, Sujit S Prabhu

Faculty, Staff and Student Publications

When operating on gliomas near critical language regions, surgeons risk either leaving residual tumor or inducing permanent postoperative language deficits (PLDs). Despite the advent of intraoperative mapping techniques, subjective judgments frequently determine important surgical decisions. We aim to inform data-driven surgery by constructing a non-invasive mapping approach that quantitatively predicts the impact of individual surgical decisions on long-term language function. This study included 79 consecutive patients undergoing resection of language-eloquent gliomas. Patients underwent preoperative navigated transcranial magnetic stimulation (TMS) language mapping to identify language-positive sites ("TMS points") and their associated white matter tracts ("TMS tracts") as well as formal language …

Role Of M6a Mrna Methylation In Plant Defense, Rakesh Srivastava, Niraj Lodhi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

N6-methyladenosine (m⁶A) is the most abundant and dynamic RNA modification in eukaryotic messenger and non-coding RNAs, playing a pivotal role in the post-transcriptional regulation of gene expression. The coordinated actions of m⁶A writers, erasers, and readers influence transcript stability, immune activation, and pathogen suppression. Growing evidence indicates that m⁶A fine-tunes the expression of defense-related genes, modulates RNA processing events, and is frequently hijacked by pathogens and pests to promote virulence. Notably, the dual role of m⁶A in enhancing plant defense and facilitating pathogen adaptation highlights its significance in the host–pathogen arms race. …

Predictors Of Long-Term Follow-Up Clinic Attendance And Continued Engagement Among Survivors Of Cancer In Childhood And Adolescence, Ji Yun Tark, Kayla L Foster, Shawki L Qasim, Omar Shakeel, Alicia Howell, Mary C Shapiro, Abiodun Oluyomi, Zoann E Dreyer, Ashley M Butler, Austin L Brown, Maria M Gramatges

Faculty, Staff and Students Publications

Purpose: Survivorship care is vital to screen for and manage late effects, yet follow-up remains suboptimal. We examined factors associated with long-term survivor clinic (LTSC) nonattendance, delayed initiation, and disengagement at a large, diverse pediatric cancer center.

Methods: We analyzed outcomes in 1138 survivorship-eligible childhood cancer survivors diagnosed between 2011 and 2019. Outcomes included (1) LTSC nonattendance (no visit ≥ 2 years post-treatment), (2) delayed LTSC visit initiation (first visit > 5 years from end of treatment), and (3) LTSC visit disengagement (no follow-up after initial LTSC visit). Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for factors associated with …

Differential Bk Channel Potentiation By Vanzacaftor Enantiomers Enables Therapy For Modulator-Ineligible People With Cystic Fibrosis, Nathalie Baumlin, Sumedha Gunewardena, Scott H Randell, Frank T Horrigan, Matthias Salathe

Faculty, Staff and Students Publications

No abstract provided.

Sub-Ciliary Localization Of Cep290 And Effects Of Its Loss In Mouse Photoreceptors During Development, Abigail R. Moye, Michael A. Robichaux, Melina A. Agosto, Alexandre P. Moulin, Alexandra Graff-Meyer, Carlo Rivolta, Theodore G. Wensel

Faculty, Staff and Students Publications

No abstract provided.

Alterations Of The Upper Respiratory Microbiome Among Children Living With Hiv Infection In Botswana, Sweta M Patel, John Farirai, Mohamed Z Patel, Sifelane Boiditswe, Leabaneng Tawe, Shimane Lekalake, Mogomotsi Matshaba, Andrew P Steenhoff, Tonya Arscott-Mills, Kristen A Feemster, Samir S Shah, Nathan Thielman, Coleen K Cunningham, Lawrence A David, David M Murdoch, Matthew S Kelly

Faculty, Staff and Students Publications

Children living with HIV (CLWH) are at high risk of colonization and infection by respiratory pathogens, though this risk can be reduced by other microbes in the upper respiratory microbiome. The impact of HIV infection on the pediatric upper respiratory microbiome is poorly understood, and we sought to address this knowledge gap by identifying associations between HIV infection and the nasopharyngeal microbiomes of Batswana children. We enrolled Batswana CLWH (< 5 years) and age- and sex-matched HIV-exposed, uninfected and HIV-unexposed, uninfected children in a cross-sectional study. We used shotgun metagenomic sequencing to compare nasopharyngeal microbiomes by HIV status. Among the 143 children in this study, HIV and HIV-associated immunosuppression were associated with alterations in nasopharyngeal microbiome composition, including lower abundances of Corynebacterium species associated with resistance to bacterial pathogen colonization. These findings suggest that the upper respiratory microbiome may contribute to the high risk of respiratory infections among CLWH.

Resilience And Vulnerabilities Of Tumor Cells Under Purine Shortage Stress, Jianpeng Yu, Chen Jin, Cheng Su, David Moon, Michael A Sun, Hong Zhang, Xue Jiang, Fan Zhang, Nomi Tserentsoodol, Michelle L Bowie, Christopher J Pirozzi, Daniel J George, Robert Wild, Xia Gao, David M Ashley, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

Purpose: Purine metabolism is a promising therapeutic target in cancer; however, how cancer cells respond to purine shortage, particularly their adaptation and vulnerabilities, remains unclear.

Experimental design: Using the recently developed purine shortage-inducing prodrug DRP-104 and genetic approaches, we investigated the responses in prostate, lung, and glioma cancer models.

Results: We demonstrate that when de novo purine biosynthesis is compromised, cancer cells employ microtubules to assemble purinosomes, multiprotein complexes of de novo purine biosynthesis enzymes that enhance purine biosynthesis efficiency. Although this process enables tumor cells to adapt to purine shortage stress, it also renders them more susceptible to the …

Stereoelectroencephalography Reveals Neural Signatures Of Multisensory Integration In The Human Superior Temporal Sulcus During Audiovisual Speech Perception, Yue Zhang, John F Magnotti, Xiang Zhang, Zhengjia Wang, Yingjia Yu, Kathryn A Davis, Sameer A Sheth, H Isaac Chen, Daniel Yoshor, Michael S Beauchamp

Faculty, Staff and Students Publications

Human speech perception is multisensory, integrating auditory information from the talker's voice with visual information from the talker's face. BOLD fMRI studies have implicated the superior temporal gyrus (STG) in processing auditory speech and the superior temporal sulcus (STS) in integrating auditory and visual speech, but as an indirect hemodynamic measure, fMRI is limited in its ability to track the rapid neural computations underlying speech perception. Using stereoelectroencephalography (sEEG) electrodes, we directly recorded from the STG and STS in 42 epilepsy patients (25F, 17M). Participants identified single words presented in auditory, visual, and audiovisual formats with and without added auditory …

Tulp3 Quantitative Alleles Titrate Requirements For Viability, Brain Development, And Kidney Homeostasis But Do Not Suppress Zfp423 Mutations In Mice, Corinne A. Mccoy, Dorothy Concepcion, Mark G. Mezody, Raquel Lara, Ojas Deshpande, Catherine Liang, Renee Long, Bruce A. Hamilton

School of Medicine Publications

Tubby-like protein 3 (TULP3) regulates receptor trafficking in primary cilia and antagonizes SHH signaling. Tulp3 knockout mice are embryonic lethal with developmental abnormalities in multiple organs, while tissue-specific knockouts and viable missense alleles cause polycystic kidney disease. Human patients with TULP3 mutations present with variable, but often multi-organ fibrotic disease. We previously showed that mouse and human Tulp3 expression is negatively regulated by ZNF423, which is required for SHH sensitivity in some progenitor cell models. The level of TULP3 function required to prevent mutant phenotypes has not been known. Here we report a Tulp3 quantitative allelic series, designed …

Percutaneous Thromboaspiration Of Left Main Coronary Artery Vegetation In A Patient With Aortic Valve Infective Endocarditis And Acute Coronary Syndrome, Matthew B Morton, Jeremy Russo, Malanka Lankaputhra, Christopher Merry, Dion Stub

Journal of the Saudi Heart Association

Acute myocardial infarction from a vegetation is a rare complication of infective endocarditis. Thrombolysis, percutaneous coronary intervention with balloon angioplasty, stenting, and thromboaspiration, and surgery have all been described in this challenging clinical scenario. A woman with staphylococcal bioprosthetic aortic valve infective endocarditis developed acute myocardial infarction due to a vegetation invading the left main coronary artery, which was successfully managed with percutaneous thromboaspiration.

Ethical Care Is Excellent Care: Exploring How Dentists Can Approach Treating Visually Impaired Patients Through Different Ethical Frameworks, Elizabeth Gershater

Journal of the American College of Dentists

The Ozar-Hasegawa Annual Student Ethics Award recognizes an outstanding scholarly submission in dental ethics, published annually in the Journal of the American College of Dentists (JACD). This article highlights the winning work, selected for its significant contribution to advancing ethical reflection and professional responsibility in dentistry.

Upholding The Social Contract In A Profit-Driven System, Kamyar Sartipi

Journal of the American College of Dentists

The Ozar-Hasegawa Annual Student Ethics Award recognizes an outstanding scholarly submission in dental ethics, published annually in the Journal of the American College of Dentists (JACD). This article highlights the winning work, selected for its significant contribution to advancing ethical reflection and professional responsibility in dentistry.

Silent Signals: Human Trafficking And The Dental Professional’S Duty To Act, Pamela Zarkowski

Journal of the American College of Dentists

Human trafficking is a global public health and human rights crisis that includes forced labor and commercial sexual exploitation. Dental professionals are uniquely positioned to recognize signs of trafficking, as many victims encounter healthcare settings, including dental offices, during their exploitation. This article introduces the types and prevalence of trafficking, outlines legal and ethical responsibilities, and provides clinical red flags, case scenarios, and actionable strategies for screening and reporting. Myths that hinder detection are also addressed. By recognizing their ethical duty to protect vulnerable patients, dental professionals can become vital allies in the identification and support of trafficking survivors.

21st-Century Dental Public Health: Revisiting The Role Of Community Water Fluoridation, Larry Williams, Preetha Kanjirath

Journal of the American College of Dentists

Community water fluoridation (CWF) has been celebrated as a major public health achievement, significantly reducing dental caries and narrowing oral health disparities. While historically effective, today’s fluoride exposure landscape has shifted, with multiple sources contributing to cumulative intake. This article reviews the scientific foundation, mechanisms of action, public health benefits, and ethical considerations surrounding CWF, alongside real-world outcomes from policy reversals. It examines contemporary concerns, including potential neurodevelopmental risks and vulnerable populations, and calls for recalibrated policies that maintain caries prevention benefits while monitoring total fluoride exposure to ensure safety in modern contexts.

The Ethical Imperative Of Preserving Federal Oversight In Academic Dentistry, Jennifer Talley, Linda Olszewski

Journal of the American College of Dentists

This article argues that federal oversight of academic dentistry by the US Department of Education (DOE) is essential to maintaining academic quality, professional standards, financial accessibility, and ethical governance. It examines the role of the DOE in the accreditation process, preserving access to financial aid, ensuring licensure eligibility, and upholding civil rights protections. The authors contend that proposals to dismantle the DOE risk undermining quality assurance, public trust, and equitable access to the profession. Without viable alternatives, preserving federal oversight remains an ethical imperative to protect students, patients, and the integrity of the dental profession.

Digital Media, Truth Decay, And The Inversion Of Trust In Science, Nicholas Mosca

Journal of the American College of Dentists

Digital media enables the rapid dissemination of scientific oral health information from subject experts to the public. However, it also poses significant risks by facilitating the dissemination of misinformation and disinformation, thereby blurring the boundaries between truth and fallacy. This paper characterizes the decay of scientific truth in policymaking, characterized by increased public debate about scientific facts and a decline in confidence in science. It describes psychological mechanisms, such as confirmation bias and motivated reasoning, and social dynamics, including algorithm-driven content distribution and echo chambers, that accelerate the circulation of misleading science information. It suggests psychological interventions to counter misinformation, …

A Wake-Up Call, Michael G. Maihofer Dds

Journal of the American College of Dentists

The Editorial is a feature in each issue of the JACD. It includes commentary on issue content, relevant topics, or other items of interest to the fellowship.

Ethical Dilemmas Surrounding Community Water Fluoridation, Roopwant Kaur, Herminio Perez, Mark Moss

Journal of the American College of Dentists

Since the 1950s, community water fluoridation (CWF) has stood as a cornerstone of dental public health. However, a growing amount of public scrutiny necessitates reflection on the ethical basis for coming to a firm position on the topic. Aside from CWF, fluoride in the form of ingestible supplements has recently been identified as a concern by the US Food and Drug Administration. Indeed, it is challenging to wade through the facts, opinions, misinformation, and policy shifts. This article examines the ethical dilemmas that surround CWF through the lens of the American Dental Association (ADA) Principles of Ethics and Code of …

J Am Coll Dent 2025 92 1

Journal of the American College of Dentists

The Journal of the American College of Dentists (JACD) publishes scholarly articles, editorials, essays, and reflections addressing the ethical, professional, and social dimensions of dentistry. The Journal serves as a forum for advancing ethics, professionalism, leadership, and excellence within the dental community. By fostering dialogue across disciplines and perspectives, JACD provides readers with insights that encourage ethical, professional practice, lifelong learning, and service to the public, reinforcing dentistry’s commitment to advancing oral healthcare and the common good.

J Am Coll Dent 2022 89 3

Journal of the American College of Dentists

The Journal of the American College of Dentists (JACD) publishes scholarly articles, editorials, essays, and reflections addressing the ethical, professional, and social dimensions of dentistry. The Journal serves as a forum for advancing ethics, professionalism, leadership, and excellence within the dental community. By fostering dialogue across disciplines and perspectives, JACD provides readers with insights that encourage ethical, professional practice, lifelong learning, and service to the public, reinforcing dentistry’s commitment to advancing oral healthcare and the common good.

J Am Coll Dent 2022 89 2

Journal of the American College of Dentists

The Journal of the American College of Dentists (JACD) publishes scholarly articles, editorials, essays, and reflections addressing the ethical, professional, and social dimensions of dentistry. The Journal serves as a forum for advancing ethics, professionalism, leadership, and excellence within the dental community. By fostering dialogue across disciplines and perspectives, JACD provides readers with insights that encourage ethical, professional practice, lifelong learning, and service to the public, reinforcing dentistry’s commitment to advancing oral healthcare and the common good.

J Am Coll Dent 2022 89 1

Journal of the American College of Dentists

The Journal of the American College of Dentists (JACD) publishes scholarly articles, editorials, essays, and reflections addressing the ethical, professional, and social dimensions of dentistry. The Journal serves as a forum for advancing ethics, professionalism, leadership, and excellence within the dental community. By fostering dialogue across disciplines and perspectives, JACD provides readers with insights that encourage ethical, professional practice, lifelong learning, and service to the public, reinforcing dentistry’s commitment to advancing oral healthcare and the common good.

J Am Coll Dent 2021 88 4

Journal of the American College of Dentists

The Journal of the American College of Dentists (JACD) publishes scholarly articles, editorials, essays, and reflections addressing the ethical, professional, and social dimensions of dentistry. The Journal serves as a forum for advancing ethics, professionalism, leadership, and excellence within the dental community. By fostering dialogue across disciplines and perspectives, JACD provides readers with insights that encourage ethical, professional practice, lifelong learning, and service to the public, reinforcing dentistry’s commitment to advancing oral healthcare and the common good.

J Am Coll Dent 2021 88 3

Journal of the American College of Dentists

The Journal of the American College of Dentists (JACD) publishes scholarly articles, editorials, essays, and reflections addressing the ethical, professional, and social dimensions of dentistry. The Journal serves as a forum for advancing ethics, professionalism, leadership, and excellence within the dental community. By fostering dialogue across disciplines and perspectives, JACD provides readers with insights that encourage ethical, professional practice, lifelong learning, and service to the public, reinforcing dentistry’s commitment to advancing oral healthcare and the common good.

J Am Coll Dent 2021 88 2

Journal of the American College of Dentists

The Journal of the American College of Dentists (JACD) publishes scholarly articles, editorials, essays, and reflections addressing the ethical, professional, and social dimensions of dentistry. The Journal serves as a forum for advancing ethics, professionalism, leadership, and excellence within the dental community. By fostering dialogue across disciplines and perspectives, JACD provides readers with insights that encourage ethical, professional practice, lifelong learning, and service to the public, reinforcing dentistry’s commitment to advancing oral healthcare and the common good.

J Am Coll Dent 2021 88 1

Journal of the American College of Dentists

The Journal of the American College of Dentists (JACD) publishes scholarly articles, editorials, essays, and reflections addressing the ethical, professional, and social dimensions of dentistry. The Journal serves as a forum for advancing ethics, professionalism, leadership, and excellence within the dental community. By fostering dialogue across disciplines and perspectives, JACD provides readers with insights that encourage ethical, professional practice, lifelong learning, and service to the public, reinforcing dentistry’s commitment to advancing oral healthcare and the common good.

J Am Coll Dent 2020 87 4

Journal of the American College of Dentists

The Journal of the American College of Dentists (JACD) publishes scholarly articles, editorials, essays, and reflections addressing the ethical, professional, and social dimensions of dentistry. The Journal serves as a forum for advancing ethics, professionalism, leadership, and excellence within the dental community. By fostering dialogue across disciplines and perspectives, JACD provides readers with insights that encourage ethical, professional practice, lifelong learning, and service to the public, reinforcing dentistry’s commitment to advancing oral healthcare and the common good.

J Am Coll Dent 2020 87 3

Journal of the American College of Dentists

The Journal of the American College of Dentists (JACD) publishes scholarly articles, editorials, essays, and reflections addressing the ethical, professional, and social dimensions of dentistry. The Journal serves as a forum for advancing ethics, professionalism, leadership, and excellence within the dental community. By fostering dialogue across disciplines and perspectives, JACD provides readers with insights that encourage ethical, professional practice, lifelong learning, and service to the public, reinforcing dentistry’s commitment to advancing oral healthcare and the common good.

J Am Coll Dent 2020 87 2

Journal of the American College of Dentists

The Journal of the American College of Dentists (JACD) publishes scholarly articles, editorials, essays, and reflections addressing the ethical, professional, and social dimensions of dentistry. The Journal serves as a forum for advancing ethics, professionalism, leadership, and excellence within the dental community. By fostering dialogue across disciplines and perspectives, JACD provides readers with insights that encourage ethical, professional practice, lifelong learning, and service to the public, reinforcing dentistry’s commitment to advancing oral healthcare and the common good.