Medical Specialties Commons^™

Down Syndrome In Africa: Challenges, Opportunities, And Future Directions, Eimear Mcglinchey, Salina Tewolde, Amanda He, Juan Fortea, Lingani Mbakile-Mahlanza, Ayda Tefera, Emmanuel Epenge, Jason Hassenstab, Rachel Maina, Zul Merali

Brain and Mind Institute

INTRODUCTION: As life expectancy improves for people with Down syndrome (DS) in Africa, the risk of developing DS-associated Alzheimer’s disease (DSAD) will rise. There is a pressing need to plan for this emerging challenge, particularly in the context of existing health and social disparities.

METHODS: This work emerged from a pan-African collaboration, including discussions at the Brain Ageing and Dementia in Low- and Middle-Income Countries conference held in Nairobi in 2024, where stakeholders identified regional priorities for DS and dementia care.

RESULTS: Limited epidemiological, cognitive, biomarker data, delayed diagnoses, and gaps in specialized services may impact access …

Protein Biomarkers Of Interstitial Lung Abnormalities In Relatives Of Patients With Pulmonary Fibrosis, Gisli Thor Axelsson, Andrea G Galecio Chao, Alan Waich, Katie Regan, Swati Gulati, Anthony H Maeda, Sharmin Sultana, Claire Cutting, Ann-Marcia C Tukpah, Andrew J Synn, Mary B Rice, Hilary J Goldberg, Joyce S Lee, David A Lynch, Rachel K Putman, Hiroto Hatabu, Benjamin A Raby, David A Schwartz, Ivan O Rosas, Gary M Hunninghake

Faculty, Staff and Students Publications

Rationale: First-degree relatives of patients with pulmonary fibrosis (referred to here as relatives) are at high risk for interstitial lung abnormalities (ILA), highlighting the need for biomarkers for risk prediction. We aimed to identify blood proteins associated with and predictive of ILA among relatives of patients with pulmonary fibrosis.

Methods: Relatives enrolled in two independent cohorts had protein levels measured using an aptamer-based proteomic platform. ILA were assessed with computed tomography scans as per Fleischner Society recommendations. Protein associations with ILA were assessed using regression. Significant proteins were used with clinical variables to detect ILA.

Results: Of 237 relatives from …

Targeting S1pr2 In Sepsis, One Fragmented Mitochondrion At A Time

Faculty, Staff and Students Publications

No abstract provided.

Aged Regulatory T Cells Fail To Control Autoimmune Lacrimal Gland Pathogenic Cd4+ T Cells, Zhiyuan Yu, Jeremias G Galletti, Cintia S De Paiva

Faculty, Staff and Students Publications

CD25KO mice are a model of Sjögren disease. CD25KO mice have severe inflammation and infiltrating lymphocytes to the lacrimal glands (LG). Whether the pathogenicity of CD25KO CD4+ T cells can be controlled in vivo by Tregs is unknown. Eight-week-old B6 and CD25KO mice LGs were submitted for RNA bulk sequencing. A total of 3481 genes were differentially expressed in CD25KO LG compared to B6. Tear washing analysis identified CD25KO mice had elevated protein levels of TNF, IFN-γ, and CCL5 and decreased protein levels of IL-12p40 and VEGF-A. Co-adoptive transfer of CD25KO CD4+ T cells with either young or aged B6 …

Temporal Changes In Risk Factors Of Hepatocellular Carcinoma In A Prospective Cirrhosis Cohort, Fasiha Kanwal, Hashem B El-Serag, Thccc Working Group, Hao Duong, Amit G Singal, Sumeet K Asrani, Themistoklis Kourkompetis, Asif Zamir, Jorge A Marrero, Ruben Hernaez, Michelle Luster, Abeer Al-Sarraj, Emad Salem

Faculty, Staff and Students Publications

No abstract provided.

Anti-Mullerian Hormone (Amh) Protects Ovarian Follicle Loss By Downregulating Granulosa Cell Function In In Vitro And In Vivo Models, Ghassan M Saed

Faculty, Staff and Students Publications

Purpose: AMH inhibits hormone production in luteinized granulosa cells (GCs) and stalls ovarian follicle development in vitro and in vivo. We sought to confirm AMH's mechanism of action through SMAD activation and investigate AMH inhibition of follicle development and function, in vitro and in vivo.

Methods: A primary culture of GCs isolated from follicular fluid was used, and cells were treated with recombinant AMH (rAMH) or placebo for 24 h. For the mouse model, 18-weeks old C57BL female mice were either euthanized at the beginning or treated with rAMH or normal saline for 3 weeks. Primordial (PDF), primary follicle (PRF), …

Author Correction: Inhibitory Specificity From A Connectomic Census Of Mouse Visual Cortex, Joann Buchanan, Daniel J Bumbarger, Leila Elabbady, Clare Gamlin, Daniel Kapner, Sam Kinn, Gayathri Mahalingam, Sharmishtaa Seshamani, Shelby Suckow, Marc Takeno, Russel Torres, Wenjing Yin, Sven Dorkenwald, J Alexander Bae, Manuel A Castro, Akhilesh Halageri, Zhen Jia, Chris Jordan, Nico Kemnitz, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, William Silversmith, Nicholas L Turner, William Wong, Jingpeng Wu, Jacob Reimer, Andreas S Tolias, H Sebastian Seung, R Clay Reid, Forrest Collman, Nuno Maçarico Da Costa

Faculty, Staff and Students Publications

No abstract provided.

Functional Mobility And Pain Are Improved For 6 Years After Adolescent Bariatric Surgery, Changchun Xie, Anita P Courcoulas, Carroll M Harmon, Michael A Helmrath, Stephanie Sisley, Marc P Michalsky, Justin R Ryder, Teen‐Longitudinal Assessment Of Bariatric Surgery (Teen‐Labs) Consortium

Faculty, Staff and Students Publications

Objective: The long-term durability of improvements in functional mobility and musculoskeletal pain for adolescents after metabolic and bariatric surgery (MBS) is unknown.

Methods: We used the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study to determine the change in mobility and pain among adolescents who underwent MBS. From standardized 400-m walk tests, we analyzed walk time, heart rate (HR) parameters, and musculoskeletal pain.

Results: The mean walk time improved from 383 s (95% CI: 368-399) prior to surgery to 351 s (95% CI: 330-372) by 6 years. The mean resting HR was 90 beats per minute (bpm; 95% CI: 87-93) preoperatively …

Longitudinal Trends In Pediatric Survival By Congenital Heart Defect In Texas, 1999 To 2017, Charles J Shumate, A J Agopian

Faculty, Staff and Student Publications

Background: Despite previously improved survival among children with congenital heart defects (CHDs), U.S. population-level evaluations of survival within recent years are scarce.

Objectives: The purpose of this study was to describe the survival landscape among children with CHDs in a large population-based birth defects registry overall and by CHD lesion.

Methods: This population-based cohort study evaluated 1999 to 2017 live births with ≥1 major CHD in the statewide Texas Birth Defects Registry. Variables included CHD lesion, demographics, gestational age at birth (term/preterm), low birthweight (< 2,500 g at birth), among others. Kaplan-Meier analyses were used to describe survival to 7 days, 28 days, 1 year, 5 years, and 10 years of life. Kaplan-Meier survival estimates were generated for 1-year survival for CHDs overall by lesion, using log-rank tests assessing differences by exposure.

Results: Of 61,656 children with CHDs, survival was 98.1% and 90.7% at 7 days and …

Early Life Exposure To Fine Particulate Matter And Fine Motor Function, Attentional Function, And Working Memory Among Spanish School-Aged Children, Wei-Jen Chen, Michael Swartz, Elaine Symanski, Antonia Valentin, Carmen Iniguez, Llúcia L González-Safont, Jesús Ibarluzea

Faculty, Staff and Student Publications

Background: Evidence of the association between fine particulate matter (PM2.5) exposure and child neuropsychological function is equivocal. We examined early life PM2.5 exposure in relation to fine motor function, attention, and working memory in early childhood.

Methods: We used data from the Spanish INfancia y Medio Ambiente Project, 2003-2008. Exposure to PM2.5 (μg/m3) was assessed using spatiotemporal land-use random forest models and assigned based on residential address histories. Around age six, children completed the finger tapping test, attentional network test (ANT), and n-back task to evaluate fine motor speed, attention, and working memory, respectively. A total of 1,310 children had …

Investigation Of Endotracheal Tube Versus Laryngeal Mask Airway Emergence Times For Surgical Patients., Samir M Patel, Rayyan Bhutta, Michelle Pershing, John Dillis, John O Elliott, Matthias J Franzen

OhioHealth Research Institute Articles

During surgical procedures requiring general anesthesia, an airway device is often placed to allow for adequate ventilation of the patient. Most commonly, endotracheal tubes (ETTs) or laryngeal mask airways (LMAs) are placed by the anesthesia provider. The difference between these two methods of ventilation is based on the location; ETTs pass through the glottis into the trachea, whereas the LMA sits above the glottis. This difference in placement may lend benefit to LMAs over ETTs, one of which includes a faster removal of the airway device. That is, after the surgical procedure is completed, there is a period when the …

Evolution Of The Family Medicine Clerkship: A Cera Secondary Analysis., Bryce A Ringwald, David Banas, Allison Macerollo, Ericka Bruce, Matthew Farrell

Medical Education Articles

BACKGROUND AND OBJECTIVES: The family medicine clerkship has been found to influence medical students' decision-making regarding specialty choice. Understanding how the family medicine clerkship has changed over the past decade may assist in recruitment efforts. Our study explored trends in family medicine clerkship design, length, and format and correlated these characteristics with high proportions of medical school graduates choosing family medicine.

METHODS: We performed a secondary analysis of the Council of Academic Family Medicine Educational Research Alliance annual family medicine clerkship director surveys from 2012 to 2023. We analyzed standard family medicine clerkship structure questions that were asked in each …

Clinicoradiological Findings And Outcome Of Posterior Reversible Encephalopathy Syndrome In Children: A Cross-Sectional Study, Zia Ur Rehman Muhammad, Shaila Ali, Shumaila Rafiq, Javeria Raza Alvi, Tipu Sultan

Pakistan Journal of Neurological Sciences (PJNS)

Background and Objective: Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome characterised by altered sensorium, seizures, visual impairment and behavioural changes. The objective of the study was to evaluate clinicoradiological findings and outcome of PRES in children.

Methods: A prospective cross-sectional study was conducted at department of pediatric neurology, the Children’s Hospital Lahore from October 2020 to September 2023. Clinical and demographic data were colllected on a structured proforma. Investigations comprised complete blood count, biochemistry, urinalysis, complement levels, inflammatory markers, immune panel, lipid profile and abdominal ultrasonography. All patients underwent MRI brain. Outcome was categorized as complete recovery or …

Silent But Deadly: A Case Of Obtuse Marginal Artery Occlusion., Austin M Miller, Vishal Tharani, Erin Fraser, Howard W Levitin

Heart and Vascular Articles

The obtuse marginal artery (OMA) is a key branch of the left circumflex coronary artery, supplying blood to the lateral wall of the left ventricle. OMA occlusions can result in myocardial ischemia and serious cardiac events, often presenting with subtle or atypical electrocardiogram (EKG) changes, unlike the more pronounced alterations observed with left anterior descending artery occlusions. This case report discusses a 57-year-old female presenting with chest pain and shortness of breath, indicative of acute coronary syndrome. The patient's initial EKG showed occasional premature ventricular contractions (PVCs), T-wave flattening in aVL, and 1 mm ST elevation in V6, but otherwise, …

Facilitators And Barriers To Neurologist Referral Of Patients For Epilepsy Surgery Evaluation., Chloé E Hill, Daniel Hochster, Jessica E Baker, Alison L Herman, Nishad Shaheid, Susanna S O'Kula, Jack M Parent, Darin B Zahuranec, Lesli E Skolarus

Neuroscience Articles

OBJECTIVE: Epilepsy surgery offers a potential cure for drug-resistant epilepsy (DRE), yet surgery is underutilized. An estimated 5% of patients with DRE undergo long-term EEG monitoring (LTM) annually, the requisite first step of evaluation for surgical candidacy. Much of the variation in LTM referral may be attributable to individual neurologist practice rather than patient characteristics. We explored neurologist behaviors and practices in epilepsy surgery referral to guide future interventions to expand patient access to surgery.

METHODS: This qualitative interview study recruited neurologists who treated adults with epilepsy. Interviews were grounded in the Theoretical Domains Framework (TDF) of behavior change to …

Validity And Reliability Of The Tampa Scale For Kinesiophobia For Adolescents With Heart Disease., David A. White, William R. Black, Emily Cramer, Lindsey Malloy-Walton, Mollie Walton, Laura Martis, Brandy Enneking, Kelli M. Teson, Jessica S. Watson, Jami Gross-Toalson

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: To assess the validity and reliability of a newly adapted Tampa Scale for KP for adolescents with HD (TSK-Heart-A).

METHODS: The TSK-Heart-A survey consists of 17 Likert scale items, producing a summary score (SS) ranging from 17 (low KP) to 68 (high KP). Following content and face validity, adolescents (age 12-18 yr) with arrhythmia disorders or Fontan palliation were recruited. The PROMIS pediatric anxiety and depression short forms, Pediatric Quality of Life Inventory (PedsQL) generic core and cardiac module, and a PA questionnaire for adolescents (PAQ-A) were used for criterion validity. The TSK-Heart-A was completed twice (20.4 ± 6.3 …

Supporting The Mental Health Of Adolescent Mothers In Kenya And Mozambique: Pilot Protocol For The Thriving Mamas Programme, Tatiana Taylor Salisbury, Maria Suzana Bata Maguele, Fernando Chissale, Málica De Melo, Margrette Hanselmann, Kethakie Lamahewa, Evaline Chepchirchir Langat, Flávio Mandlate, Lucy Nyaga, Marleen Temmerman

Centre of Excellence in Women and Child Health

Background: Poor mental health among adolescent girls during pregnancy and the year after birth (the perinatal period) has been found to have a significant detrimental effect on girls and their children. The Innovative approaches to adolescent perinatal wellbeing (INSPIRE) project co-designed an intervention (Thriving Mamas) to improve adolescent perinatal mental health in Kenya and Mozambique. The aim of the current study is to pilot test the co-designed intervention to understand how it can be adapted for further testing or scale-up.

Methods :A mixed-method, pilot cluster-randomised, efectiveness-implementation Hybrid Type II trial will be conducted among 80 adolescent girls (aged 15–19 years) …

Glutamatergic Regulation Of Mirna-Containing Intraluminal Vesicle Trafficking And Extracellular Vesicle Secretion From Cortical Neurons, Rashed Alananzeh, Jiaqian Wu, Yongjie Yang

Faculty, Staff and Student Publications

Neuronal extracellular vesicles (microvesicles and exosomes) are emerging secreted vesicular signals that play important roles in the CNS. Currently, little is known about how glutamatergic signalling affects the subcellular localisation of exosome precursor intraluminal vesicles (ILVs), microRNA (miR) packaging into ILVs and in vivo spreading of neuronal EVs. By selectively labelling ILVs and exosomes (but not plasma membrane-derived MVs) with GFP-tagged human CD63 (hCD63-GFP) in cortical neurons, we found that glutamate stimulation significantly redistributes subcellular localisation of hCD63-GFP+ ILVs, especially decreasing its co-localisation with multi-vesicular body (MVB) marker Rab7 while substantially promoting EV secretion. Interestingly, glutamate stimulation only modestly alters …

Ao Spine Clinical Practice Recommendations For Diagnosis And Management Of Degenerative Cervical Myelopathy: Evidence Based Decision Making - A Review Of Cutting Edge Recent Literature Related To Degenerative Cervical Myelopathy, Daipayan Guha, Chris J Neal, Benjamin M Davies, Mario Ganau, Jefferson R Wilson, Allan R Martin, Lukas Grassner, Lindsay Tetreault, Vafa Rahimi-Movaghar, Rex Marco, James Harrop, James Guest, Mohammed Ali Alvi, Karlo M Pedro, Brian K Kwon, Charles G Fisher, Shekar N Kurpad

Faculty, Staff and Student Publications

Study Design

Literature review of key topics related to degenerative cervical myelopathy (DCM) with critical appraisal and clinical recommendations.

Objective

This article summarizes several key current topics related to the management of DCM.

Methods

Recent literature related to the management of DCM was reviewed. Four articles were selected and critically appraised. Recommendations were graded as Strong or Conditional.

Results

Article 1: The Relationship Between pre-operative MRI Signal Intensity and outcomes. Conditional recommendation to use diffusion-weighted imaging MR signal changes in the cervical cord to evaluate prognosis following surgical intervention for DCM. Article 2: Efficacy and Safety of Surgery for Mild …

Association Of Sars-Cov-2 With Health-Related Quality Of Life 1 Year After Illness Using Latent Transition Analysis, Lauren Wisk, Michael Gottlieb, Peizheng Chen, Huihui Yu, Kelli O'Laughlin, Kari Stephens, Graham Nichol, Juan Carlos Montoy, Robert Rodriguez, Michelle Santangelo, Kristyn Gatling, Erica Spatz, Arjun Venkatesh, Kristin Rising, Mandy Hill, Ryan Huebinger, Ahamed Idris, Michael Willis, Efrat Kean, Samuel Mcdonald, Joann Elmore, Robert Weinstein

Department of Emergency Medicine Faculty Papers

BACKGROUND: Long-term sequelae after SARS-CoV-2 infection may impact health-related quality-of-life (HRQoL), yet it is unknown how HRQoL changes during recovery. We compared patient-reported HRQoL among adults with COVID-19-like illness who tested SARS-CoV-2 positive (COVID+) with those who tested negative (COVID-).

METHODS: Participants in this prospective, multicenter, longitudinal registry study were enrolled from December 2020 through August 2022 and completed 3-month follow-up assessments until 12 months after enrollment. Participants were adults (≥18 years) with acute symptoms suggestive of COVID-19 who received a Food and Drug Administration-approved SARS-CoV-2 test. Participants received questions from PROMIS-29 (subscales: physical function, anxiety, depression, fatigue, social participation, …

Assessment Of Emergency Medicine Residents' Situational Awareness And Perception Of Patient Safety Culture In The Emergency Department, Adriana Olson, Nathan Olson, Nicholas Hartman, Casey Morrone, Morgan Battaglia, Kamna Balhara

Department of Emergency Medicine Faculty Papers

BACKGROUND: Situational awareness (SA) and positive safety climate are crucial to patient safety. Little is known about emergency medicine (EM) trainees' SA and perception of emergency department (ED) safety climate, and the interactions of those factors with safety-related behaviors.

OBJECTIVES: Our objective was to evaluate EM residents' perceptions of ED safety climate, self-reported SA, and comfort with identifying, rectifying, and reporting safety hazards.

METHODS: In this cross-sectional study at two EM residencies, residents completed the Situational Awareness Rating Technique (SART) after ED-based or simulated resuscitations as well as a survey regarding safety climate and comfort with identifying, rectifying, and reporting …

A Rare Sequela Of Untreated Streptococcus Pharyngitis: A Case Report., Meredith Hiltbrand Lehoe, Emily Cushing

Ambulatory and Primary Care Articles

Pharyngitis is commonly caused by the gram positive bacteria, streptococcus. Given the potential morbid complications of untreated streptococcal pharyngitis, antibiotics are critical. One of the rarer complications is pulmonary-renal syndrome (PRS), defined as rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage. PRS is associated with high rates of morbidity and mortality, making swift diagnosis and treatment imperative for survival. More common causes of PRS are tied to autoimmune diseases. This case describes a novel progression of PRS caused by streptococcus. A 26-year-old male with no significant medical history presented to our emergency department with streptococcal group A-positive sore throat. After discontinuing …

Enhanced Hair Regrowth With Five Monthly Sessions Of Minoxidil-Dutasteride-Copper Peptides Tattooing For Androgenetic Alopecia Assessed By Artificial Intelligence And Blinded Evaluators., Guilherme Kuceki, Austin J Coppinger, Sara D Ragi, Luke S Johnson, Andy Goren, Luiza L Kalil, Pablo Cirino, Carlos G Wambier

Ambulatory and Primary Care Articles

No abstract provided.

Encoding 3d Information In 2d Feature Maps For Brain Ct-Angiography, Uma M Lal-Trehan Estrada, Sunil Sheth, Arnau Oliver, Xavier Lladó, Luca Giancardo

Faculty, Staff and Student Publications

We propose learnable 3D pooling (L3P), a CNN module designed to compress 3D information into 2D feature maps using anisotropic convolutions and unidirectional max pooling. Specifically, we used L3P followed by a 2D network to generate predictions from 3D brain CT-Angiography (CTA) in the context of large vessel occlusion (LVO). To further demonstrate its versatility, we extended its application to 3D brain MRI analysis for brain age prediction. First, we designed an experiment to classify the LVO-affected hemisphere (left or right), projecting the input CTA into the sagittal plane, which allowed to assess the ability of L3P to encode the …

A Plain Language Summary Of The Molecular Changes In The Tumors Of People With Braf V600e-Mutant Colorectal Cancer In The Beacon Study, Scott Kopetz, Danielle A Murphy, Jie Pu, Fortunato Ciardiello, Jayesh Desai, Harpreet Singh Wasan, Hedieh Saffari, Xiaosong Zhang, Phineas Hamilton, Tao Xie, Rona Yaeger, Josep Tabernero

Faculty, Staff and Student Publications

What is this summary about?This summary discusses the genetic and molecular changes in tumors of participants with BRAF V600E–mutant metastatic colorectal cancer who were treated with encorafenib plus cetuximab, with or without binimetinib, in the BEACON study.

What were the results?Encorafenib plus cetuximab, with or without binimetinib, reduced the risk of participants dying compared with cetuximab plus chemotherapy, regardless of genetic or molecular colorectal cancer subtypes.The study also found genetic and molecular changes in the participants’ tumors during treatment that were associated with how long they lived.

What do the results of the study mean?The types of …

Cll Cell-Derived Exosomes Alter The Immune And Hematopoietic Systems, Ivo Veletic, David M Harris, Uri Rozovski, Maria Teresa S Bertilaccio, George A Calin, Ping Li, Taghi Manshouri, Rares-Constantin Drula, Ken Furudate, Muharrem Muftuoglu, Anwar Hossain, William G Wierda, Michael J Keating, Zeev Estrov

Faculty, Staff and Student Publications

The origins of immunosuppression, neutropenia, and anemia in patients with chronic lymphocytic leukemia (CLL) are not fully understood. Because in patients with CLL, circulating exosomes, which participate in cell-to-cell interactions, are CLL cell-derived, we examined whether those exosomes contribute to abnormal features of this disease. Our data revealed that CLL cell-derived exosomes engulfed by healthy donors’ monocytes, fibrocytes, and lymphocytes altered target-cell gene and protein expression and suppressed normal hematopoiesis. CLL cell-derived exosomes increased normal monocytes’ CD14 and CD16 expression such that it mimicked the accessory cell profile and upregulated T cells’ checkpoint PD-1 and CD160 protein levels, potentially reducing …

Emerging Technologies Of Single-Cell Multi-Omics, Yi June Kim, Koichi Takahashi

Faculty, Staff and Student Publications

The heterogeneity of the hematopoietic system was largely veiled by traditional bulk sequencing methods, which measure the averaged signals from mixed cellular populations. In contrast, single-cell sequencing has enabled the direct measurement of individual signals from each cell, significantly enhancing our ability to unveil such heterogeneity. Building on these advances, numerous single-cell multi-omics techniques have been developed into high-throughput, routinely accessible platforms, delineating the precise relationships among different layers of the central dogma in molecular biology. These technologies have uncovered the intricate landscape of genetic clonality and transcriptional heterogeneity in both normal and malignant hematopoietic systems, highlighting their roles in …

Targeted Sting Activation Using Modified Ultrasound-Responsive Microbubbles Enhances Immune Checkpoint Blockade Against Melanoma, Sina Khorsandi, Kristin Huntoon, Yifan Wang, Adam Woodward, Abin Antony, Nazia Hafeez, Nicole Mccuen, Prasanna G Alluri, Betty Y S Kim, Wen Jiang, Jacques Lux

Faculty, Staff and Student Publications

Despite the recent successes of immune checkpoint inhibitors (ICIs) in treating advanced melanoma, durable clinical responses still remain limited. To boost immune responses, agents that target immune regulators, such as the Stimulator of Interferon Genes (STING) agonist cyclic GMP-AMP (cGAMP), are being investigated. However, their clinical translation is impeded by poor serum stability, rapid tissue clearance, and T-cell death due to off-target activation. Recently, a novel strategy termed Microbubble-assisted UltraSound-guided Immunotherapy of Cancer (MUSIC) has been reported to selectively deliver cGAMP directly into the cytosol of antigen-presenting cells with spatiotemporal control. The resulting activation of STING and downstream proinflammatory pathways …

International Expert-Based Consensus Definition, Classification Criteria, And Minimum Data Elements For Osteoradionecrosis Of The Jaw: An Interdisciplinary Modified Delphi Study, Amy C Moreno, Erin E Watson, Laia Humbert-Vidan, Douglas E Peterson, Lisanne V Van Dijk, Lisa Van Den Bosch, Matthew S Katz, Frank J P Hoebers, Ruth A Aponte Wesson, James E Bates, Paolo Bossi, Adeyinka F Dayo, Mélanie Doré, Eduardo Rodrigues Fregnani, Thomas J Galloway, Daphna Y Gelblum, Issa A Hanna, Christina E Henson, Sudarat Kiat-Amnuay, Anke Korfage, Nancy Y Lee, Carol M Lewis, Charlotte Duch Lynggaard, Antti A Mäkitie, Marco Magalhaes, Yvonne M Mowery, Carles Muñoz-Montplet, Jeffrey N Myers, Ester Orlandi, Jaymit Patel, Jillian M Rigert, Deborah Saunders, Jonathan D Schoenfeld, Ugur Selek, Efsun Somay, Vinita Takiar, Juliette Thariat, Gerda M Verduijn, Alessandro Villa, Nicholas S West, Max J H Witjes, Alex M Won, Mark E Wong, Christopher M K L Yao, Simon W Young, Kamal Al-Eryani, Carly E A Barbon, Doke J M Buurman, François J Dieleman, Theresa M Hofstede, Abdul Ahad Khan, Adegbenga O Otun, John C Robinson, Lauren Hum, Jorgen Johansen, Rajesh Lalla, Alexander Lin, Vinod Patel, Richard J Shaw, Mark S Chambers, Daniel Ma, Mabi Singh, Noam Yarom, Abdallah Sherif Radwan Mohamed, Katherine A Hutcheson, Stephen Y Lai, Clifton David Fuller

Faculty, Staff and Student Publications

Purpose: Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy to the head and neck. With >9 published definitions and at least 16 classification systems, the true incidence and severity of ORNJ are obscured by lack of a standard for disease definition and severity assessment, leading to inaccurate estimation of incidence, reporting ambiguity, and likely underdiagnosis worldwide. This study aimed to achieve consensus on an explicit definition and phenotype of ORNJ and related precursor states through data standardization to facilitate effective diagnosis, monitoring, and multidisciplinary management of ORNJ.

Methods and materials: The …

Gsk-3484862, A Dnmt1 Degrader, Promotes Dnmt3b Expression In Lung Cancer Cells, Qin Chen, Swanand Hardikar, Kimie Kondo, Nan Dai, Ivan R Corrêa Jr, Marcos R Estecio, Taiping Chen, Xiaodong Cheng

Faculty, Staff and Student Publications

DNA methylation alterations, including hypermethylation and silencing of tumor suppressor genes, contribute to cancer formation and progression. The FDA-approved nucleoside analogs azacytidine and decitabine are effective demethylating agents for hematologic malignancies but their general use has been limited by their toxicity and ineffectiveness against solid tumors. GSK-3484862, a dicyanopyridine-containing, DNMT1-selective inhibitor and degrader, offers a promising lead for developing novel demethylating therapeutics. Here, we demonstrate that GSK-3484862 treatment upregulates DNMT3B expression in lung cancer cell lines (A549 and NCI-H1299). Disrupting DNMT3B in NCI-H1299 sensitizes these cells to GSK-3484862, enhancing its inhibitory effects on cell viability and growth. GSK-3484862 treatment induces …