Digital Commons Network^™

An Interoperable Vaccine Record: A Roadmap To Realization, Xia Jing, Arild Faxvaag, Christian G Nøhr, David Robinson, Paul G Biondich, Timothy D Law, Hua Min, Adam Wright, Yang Gong, Dean F Sittig

Faculty, Staff and Student Publications

Objectives: The objectives of this study were to educate the healthcare professional and the general public about interoperable vaccine records by elaborating on its definition, why we need one, what the challenges are, and what progress has been made in this direction.

Methods: The vaccination practices and vaccine record-keeping in the Nordic countries, the UK, and the USA are used as examples to demonstrate the necessity of interoperable vaccine records. The authors' expertise and experience in interoperability, medicine, and HealthIT, along with the literature, informed this paper's content, structure, and organization. Real-world examples and scenarios illustrate the reality …

From Wrist Data To Lifespan: Elucidating Inflammation-Driven Biological Aging Via Activity Rhythms Captured By Wearable Devices, Jinjoo Shim, Faraz Bishehsari, Mahboobeh Mahdavinia, Jamie M Zeitzer, Elgar Fleisch, Filipe Barata

Faculty, Staff and Student Publications

Systemic inflammation ("inflammaging") accelerates biological aging and drives cardiovascular, metabolic, and neurodegenerative disease. Circadian rhythms regulate the amplitude and timing of immune responses, yet their mechanistic role in inflammation and longevity remains unexplored. In 62,000 adults with 7-day wearable accelerometry, interpretable machine learning model identified rhythm amplitude, stability, and moderate-to-vigorous physical activity (MVPA) as dominant predictors of accelerated aging. In a subset of 1521 participants (35% male) with available data on the systemic immune-inflammation index (SII), we further examined the associations between behavioral rhythmicity and inflammation. Low amplitude and poor rhythm stability were associated with 0.31 and 0.18 SD higher …

Pretreatment Risk Model For Radiation-Induced Lymphopenia Is Associated With Adjuvant Durvalumab Efficacy In Patients With Unresectable Stage Iii Nsclc, Peter S N Van Rossum, Pim J J Damen, Francesco Cortiula, Brian P Hobbs, Lorenzo De Marchi, Radhe Mohan, Max Peters, Famke L Schneiders, Dirk De Ruysscher, Robin Wijsman, Joost J C Verhoeff, Ting Xu, Zhongxing Liao, Steven H Lin

Faculty, Staff and Student Publications

Introduction: Severe radiation-induced lymphopenia (RIL) during concurrent chemoradiotherapy (CCRT) for NSCLC has been associated with poorer outcomes and reduced immunotherapy efficacy. Because RIL often develops late during CCRT, identifying patients at risk before treatment may be clinically relevant. This study aimed to develop and validate a nomogram based on pretreatment predictors for severe RIL, and secondarily to explore associations between predicted RIL risk and adjuvant durvalumab-associated survival.

Methods: A retrospective development cohort of consecutive patients with NSCLC treated with CCRT (2010-2019) was established, along with an independent external validation cohort from other institutions. A multivariable logistic regression model was developed …

Development And Validation Of A Prognostic Risk Score For Patients With Cancer And Neutropenic Fever Presenting To The Emergency Department, Sandy Nath, Aiham Qdaisat, Andriy Derkach, Afia Babar, Deepti Zalavadia, Patrick Chaftari, Ziyi Li, Monica K Wattana, Joseph Schmeltz, Rocio Perez Johnston, Eduardo Ortiz, Kumar Alagappan, Adam Klotz, Sai-Ching Jim Yeung

Faculty, Staff and Student Publications

Objectives: Neutropenic fever (NF) is a life-threatening oncologic emergency associated with significant morbidity and mortality. Current predictive risk-stratification scores' limitations include outdated criteria, subjectivity, and low usage in the emergency department (ED). We sought to develop and externally validate a pragmatic, objective risk score to predict adverse outcomes in patients presenting to the ED with cancer and NF.

Methods: A retrospective cohort study was performed using data from 2 comprehensive cancer centers. The derivation cohort included adults presenting with NF to Memorial Sloan Kettering Cancer Center. External validation was conducted using data from the MD Anderson Cancer Center. The primary …

Therapeutic Plateletpheresis For Thrombocytosis: Critical Analytic Reviews And Original Multicenter Experience, Jensyn Cone Sullivan, Jay S Raval, Nicole D Zantek, David L Allison, Gaurav Gupta, Caroline R Alquist, Nour Al Mozain, Hlaing Tint, Louise Helander, Lisa Boggio, Jose Pérez-Carrillo, Kyle Annen

Faculty, Staff and Student Publications

Primary thrombocytosis is associated with increased risk of thromboembolism and bleeding. Therapeutic plateletpheresis (TPP), capable of rapid, transient platelet (Plt) count reduction, is employed as an emergency intervention for symptomatic thrombocytosis while awaiting the therapeutic effect of medical cytoreductive therapy. Nonetheless, the effect of TPP on outcomes and optimal role for TPP remain poorly understood. Critical analytic review of highest-pertinence and -quality articles was performed with the goal of establishing current knowledge gaps to direct original case data collection. Retrospective review of TPP procedures at six United States sites over ten years was performed. Pre-TPP symptoms, medical cytoreduction, adverse events …

Frequency And Self-Reported Outcomes Of Transcranial Magnetic Stimulation For Obsessive Compulsive Disorder In The U.S. And Latin America, Hala Aziz, Guadalupe Vidal-Martinez, Ogechi C Onyeka, Jacey L Anderberg, Javier Vargas-Medrano, Diana Sotelo, Demi Kourtesi, Renee M Frederick, Josselyn S Muñoz, Dayan Berrones, Vanessa Zavala Cruz, Peter Thompson, Silvina Tonarelli, Andrew D Wiese, James J Crowley, Eric A Storch

Faculty, Staff and Students Publications

Introduction: Obsessive compulsive disorder (OCD) affects about 1-2% of the global population, with roughly 30% of patients not responding to first-line treatments. Transcranial Magnetic Stimulation (TMS) has some support for treatment-resistant OCD but global use is unclear.

Methods: This study describes the frequency with which TMS was reported to be received among a large cohort of individuals who self-identified as Latino-Hispanic in Latin America and the United States. Among 3,391 participants, 76 (2.2%) had completed TMS for OCD.

Results: Recipients who received TMS exhibited more severe current and lifetime OCD symptoms compared to non-recipients. On average, participants underwent 22.61 TMS …

Coordinated Stimulation Of Axon Regenerative And Neurodegenerative Transcriptional Programs By Atf4 Following Optic Nerve Injury, Preethi Somasundaram, Madeline M Farley, Melissa A Rudy, Katya Sigal, Andoni I Asencor, David G Stefanoff, Malay Shah, Puneetha Goli, Jenny Heo, Shufang Wang, Nicholas M Tran, Trent A Watkins

Faculty, Staff and Students Publications

Stress signaling is important for determining the fates of neurons following axonal insults. Previously, we showed that the stress-responsive kinase PERK contributes to injury-induced neurodegeneration (Larhammar et al., 2017). Here, we show that PERK acts primarily through activating transcription factor-4 (ATF4) to stimulate not only pro-apoptotic but also pro-regenerative responses following optic nerve damage. Using conditional knockout mice, we find an extensive PERK/ATF4-dependent transcriptional response that includes canonical ATF4 target genes and modest contributions by C/EBP Homologous Protein (CHOP). Overlap with c-Jun-dependent transcription suggests interplay with a parallel stress pathway that orchestrates regenerative and apoptotic responses. Accordingly, neuronal knockout of …

Merritt-Putnam Symposium | Tumor-Associated Epilepsy And Epilepsy-Associated Tumors: Exploring The Bidirectional Crosstalk Between Tumors And Seizures, Tracy A Bedrosian, Michael Wong, Erin L Heinzen, Benjamin Deneen, Catherine A Christian-Hinman

Faculty, Staff and Students Publications

Links between cancerous and noncancerous brain tumors and epilepsy have long been recognized. However, recent clinical and preclinical studies emphasize that not only do tumors impinge on surrounding brain tissue in ways that promote hyperexcitability and epileptogenesis, but that neural activity also influences tumor progression. In this review, inspired by the Merritt-Putnam Symposium of the 2025 meeting of the American Epilepsy Society, we present a cross-disciplinary dialog between cancer and epilepsy research, including discussion of tumors and epilepsies that are more prominent in pediatric versus adult populations. First, we discuss the neuropathology, genetics, and surgical outcomes of epileptogenic brain tumors, …

Bacteriophage-Mediated Reduction Of Uropathogenic E Coli From The Urogenital Epithelium, Bishnu Joshi, Jacob J Zulk, Camille Serchejian, Zainab A Hameed, Addison B Larson, Austen L Terwilliger, Deepak Kumar, Indira U Mysorekar, Robert A Britton, Anthony W Maresso, Kathryn A Patras

Center on Aging Staff Publications

Urinary tract infections (UTIs), primarily caused by uropathogenic Escherichia coli (UPEC), affect millions annually. UPEC gains access to the urinary tract through mucosal reservoirs, including the vaginal tract. With rising antibiotic resistance and frequent recurrence, alternative non-antibiotic strategies like bacteriophage (phage) therapy are gaining attention. We explored the potential of a lytic phage, ΦHP3, as well as a phage cocktail to decolonize UPEC from the urogenital tract using in vitro and in vivo models. Phage demonstrated replication and lytic activity in both bacteriologic medium and simulated vaginal fluid. Pretreatment of human vaginal epithelial cells (VK2/E6E7) and bladder carcinoma cells (HTB-9) …

Intouch Week Of February 23, 2026, New York Medical College

InTouch

• Keep Your Heart Healthy This February
• TCDM and NYMC Students Volunteer at Guidance Center of Westchester
• Off Campus, On Craft: Ralph Torres Keeps Campus Operations Flying High

Adjunctive Hyperbaric Oxygen Therapy For Chronic Diabetic Foot Ulcer Unresponsive To Standard Care: A Case Report, Ismail Ismail, Sukriyadi Adi, Sitti Rahmatia, Agustan Agustan

BioMedicine

Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes mellitus and are often challenging to treat, particularly in patients who fail to respond to standard wound care. Adjunctive therapies such as hyperbaric oxygen therapy (HBOT) have shown potential in promoting wound healing in chronic cases.

Case Presentation: A 66-year-old male with a 10-year history of type 2 diabetes mellitus presented with a chronic, non-healing DFU on the right foot. Despite oral antibiotic therapy and conventional wound management, the ulcer demonstrated progressive necrosis, persistent infection, and tissue exposure. Wound culture identified Klebsiella oxytoca. After targeted antibiotic treatment, the patient …

Neurosurgical Management Of Pineal Lesions: Insights From A Single-Center Study Of 27 Cases, David Montesinos Contreras, Walter Stummer, Maryam Khaleghi Ghadiri

BioMedicine

Introduction: Pineal lesions are rare and surgically challenging due to their deep location, histological diversity, and potential malignancy. The complexity of the pineal region anatomy and the diverse pathological spectrum contribute to the lack of standardized treatment strategies, making appropriate management controversial. Aim: This study aimed to evaluate the surgical outcomes of patients with pineal tumors or cysts and to assess the impact of different surgical approaches, particularly the extent of resection, on progression-free survival. Methods: We conducted a retrospective analysis of 27 patients treated for pineal tumors or cysts at our institution between 2010 and 2020. Data regarding clinical …

A Glimpse Into The Impact Of Physical Activity On Linear Growth In Children And Adolescents Through Activity Restrictions Accompanying The Covid-19 Outbreak, Yi-Chun Lin, Wen-Ling Liao, Chung-Hsing Wang, Fuu-Jen Tsai

BioMedicine

Background: Linear growth in children and adolescents, a key health indicator, is influenced by various factors, including physical activity (PA). The COVID-19 lockdown in Taiwan created a unique opportunity to examine the effect of PA restrictions on growth.

Methods: This retrospective cohort study was conducted at two hospitals in central Taiwan. The study included 72 children and adolescents (26 males, 46 females) who attended a growth clinic. Height and weight measurements were recorded in three stages: pre-lockdown, during lockdown, and post-lockdown. Growth rates were compared across stages using paired t-tests.

Results: The average growth rate was lowest during lockdown (0.0181 …

Assessing The Capabilities Of Ai-Based Large Language Models (Ai-Llms) In Interpreting Histopathological Slides And Scientific Figures: Performance Evaluation Study, Khanisyah Erza Gumilar, Grace Ariani, Priangga A. Wiratama, Rimbun Rimbun, Tri H. Yuliawati, Hong Chen, Ibrahim H. Ibrahim

BioMedicine

Background: Integrating artificial intelligence-based large language models (AI-LLMs) into medical and other scientific domains is increasingly recognized as a tool to support complex tasks, such as interpreting histopathology slides and scientific figures. AI-LLMs can simplify these processes by providing clearer explanations. By improving accessibility and comprehension, AI-LLMs can significantly assist healthcare professionals in diagnosing and therapy determination. Students and the public also find it easier to understand complex scientific concepts and images.

Objectives: This study explores the capability of AI-LLMs in interpreting histopathological slides and scientific images. This study aims to evaluate the performance of AI-LLMs in supporting diagnostics and …

Decyl Caffeate Inhibits The Proliferation Of Human Triple-Negative Breast Cancer Cells, Che-Yi Chao, Woei-Cheang Shyu, Chih-Lung Lin, En-Pei Isabel Chiang, Yueh-Hsiung Kuo, Feng-Yao Tang

BioMedicine

Background: Over recent decades, considerable attention has been directed toward the discovery of novel compounds capable of targeting survival-related signaling networks as therapeutic candidates for triple-negative breast cancer (TNBC). Central to TNBC pathobiology are the Akt/mTOR and MAPK/ERK signaling axes, both contribute to tumor progression and therapeutic resistance. Caffeic acid (CA), a naturally derived phenolic compound with anti-inflammatory activity, has previously been investigated for its anti-cancer potential. Purpose: In the present study, we explored the therapeutic value of newly synthesized CA derivatives in TNBC models using both cellular and animal-based systems. Methods: The anti-tumor efficacy of these CA derivatives was …

The Association Between The Gnb3 Rs5443 C/C Genotype And Obesity Phenotypes In Taiwanese Individuals, Ling-Yi Xiao, Zi-Lun Lai, Yang-Di Su, Szu-Yun Wang, Nia-Jia Zheng, Po- Ren Hsueh

BioMedicine

Background: The prevalence of obesity has increased significantly over the

years, and its health concerns cannot be underestimated. Obesity not only

causes potential mobility limitations in daily life but also increases the risk of

developing cardiovascular diseases, diabetes, cancer and other health

conditions. While an imbalanced diet and lack of exercise are well-known

causes of obesity, genetic patterns also influence its development. Although the GNB3 gene is known to be involved in lipid metabolism and fat cell

differentiation, studies have shown inconsistent associations between a

common single nucleotide polymorphism of GNB3 (c.825C>T, rs5443) and

obesity across different populations. Therefore, …

Chinese Herbal Medicine Treatment And The Association With Long-Term Major Adverse Cardiac Events In Patients With Chronic Kidney Disease: A Propensity-Score Matched Cohort Study, Yuan-Ching Liao, Mei-Yao Wu, Cheng-Li Lin, Chiz-Tzung Chang, Peter Mayer, Hung-Rong Yen

BioMedicine

Background: Cardiovascular disease (CVD) represents the leading cause of

mortality among idividuals with chronic kidney disease (CKD). While Chinese herbal

medicine (CHM) is commonly used by CKD patients in Taiwan, the impact of CHM

use on cardiovascular outcomes in this population remains insufficiently understood.

Aims: This study aimed to evaluate the association between CHM use and the long-

term risk of major adverse cardiac events (MACEs) in patients with CKD.

Methods: Data were obtained from the Taiwan National Health Insurance Research Database to identify patients aged over 20 years with newly diagnosed CKD. A 1:1 propensity score matching was performed …

Increased Dairy Product Consumption Is Associated With Shorter Telomere Length In Buccal Cells Among Normotensive Adults, Hsin-Hwa Tsai, Yang-Di Su, Zi-Lun Lai, Chia-Yu Lin, Shu-Fan Lin, Hsiu-Ching Hsu, Wen-Yuan Lin, Po-Ren Hsueh

BioMedicine

Background: Telomere length (TL) is a biomarker of biological aging and a predictor of age-related diseases. Dietary patterns, including dairy consumption, may influence telomere dynamics, but the evidence remains limited, particularly in Asian populations. This study investigates the association between dairy consumption and relative telomere length (RTL) in Taiwanese adults, with results analyzed by hypertension status.

Methods: A cross-sectional survey was conducted among 259 adults in Taipei, Taiwan. RTL was measured using quantitative PCR from buccal cells. Dietary intake was assessed through self-reported questionnaires, with a focus on dairy frequency and fat content. Multiple linear regression models were used to …

Osteopathic Manipulative Treatment Vs. Standard Therapy In The Management Of Acute Neck And Low Back Pain In The Emergency Department, Steven M Hochman, Katherine Vlasica, Alexis Lapietra, Bhargavi K Patel, Christine Ju, Nicholas J Mota, Scott Wilder

Faculty, Staff and Student Publications

Context: Acute neck and low back pain are common emergency department (ED) presentations, generally treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Osteopathic manipulative treatment (OMT) is a hands-on treatment modality utilized to treat a variety of musculoskeletal conditions.

Objectives: We sought to evaluate the relative efficacies and side effects of hands-on OMT vs. one dose of oral ibuprofen, in the treatment of adult patients presenting with acute neck or back pain.

Methods: We conducted a prospective randomized controlled trial at a high-volume urban ED. Adult patients with acute neck or low back pain were randomized to 5 min of OMT or …

Response To "Pulmonary Hypertension As A Determinant Of In-Hospital Mortality In Copd: Insights And Methodological Considerations", Trishna Parikh, Saad Afzal Khan, Adishwar Rao, Bela Patel, Bindu Akkanti

Faculty, Staff and Student Publications

No abstract provided.

Social Roles And Emotional Distress Are Associated With Successful Aging In Adult Childhood Cancer Survivors, Samah Hayek, Kimberly A Miller, Michael E Roth, Michelle A T Hildebrandt, David R Freyer, Joel Milam

Faculty, Staff and Student Publications

Childhood cancer survivors (CCS) face complex long-term health consequences resulting from intensive treatments that may impact their aging trajectory. This study assessed the associations between social role attainment, emotional distress, and indicators of successful aging (SA) among adult CCS, considering treatment intensity. SA, is a multidimensional concept encompassing physical, cognitive, and psychosocial well-being, provides a framework for understanding and optimizing outcomes in this population. This cross-sectional study utilized data from Project Forward, a cohort, of 1,248 adult CCS diagnosed between 1996 and 2010. Participants were identified through the Los Angeles County Cancer Surveillance Program and completed a comprehensive self-report survey …

Respiratory Syncytial Virus Co-Detection With Other Respiratory Viruses Is Not Significantly Associated With Worse Clinical Outcomes Among Children Aged <2 Years: New Vaccine Surveillance Network, 2016-2020, Justin Z Amarin, Ariana P Toepfer, Andrew J Spieker, Haya Hayek, Tess Stopczynski, Yasmeen Z Qwaider, Laura S Stewart, James D Chappell, Mary Allen Staat, Elizabeth P Schlaudecker, Geoffrey A Weinberg, Peter G Szilagyi, Janet A Englund, Eileen J Klein, Marian G Michaels, John V Williams, Rangaraj Selvarangan, Christopher J Harrison, Leila C Sahni, Vasanthi Avadhanula, Meredith L Mcmorrow, Heidi L Moline, Natasha B Halasa

Faculty, Staff and Students Publications

Background: Risk factors for severe respiratory syncytial virus (RSV) illness include early infancy, premature birth, and underlying medical conditions. However, the clinical significance of respiratory viral co-detection is unclear. We compared the clinical outcomes of young children with RSV-only detection and those with RSV viral co-detection.

Methods: We conducted active, population-based surveillance of children with medically attended fever or respiratory symptoms at 7 US medical centers (1 December 2016-31 March 2020). Demographic and clinical data were collected through parental interviews and chart abstractions. Nasal swabs, with or without throat swabs, were systematically tested for RSV and 6 other common respiratory …

Concordance Analysis Of Dna And Rna Profiling: The Md Anderson Impact2 Study In Precision Oncology, Stephanie T Schmidt, Mehmet A Baysal, Siqing Fu, David S Hong, Sarina A Piha-Paul, Aung Naing, Jordi Rodon Ahnert, Timothy A Yap, Ecaterina Elena Dumbrava, Jennifer Beck, Funda Meric-Bernstam, Apostolia Maria Tsimberidou

Faculty, Staff and Student Publications

DNA profiling is an established method for cancer treatment selection, while RNA profiling remains investigational. We explored associations between DNA and RNA alterations and between the number of genes with altered expression and overall survival (OS) using patient data from IMPACT2 (NCT02152254), a randomized study evaluating molecular profiling for guiding cancer therapy across tumor types. Molecular profiling, including DNA next-generation sequencing, was performed on all 829 patients in the IMPACT2 study. RNA profiling was performed by Tempus for 253 of 829 patients. We evaluated the concordance between DNA and RNA profiling, analyzed OS in 217 treated patients with …

Risk Stratification Of Low-Dose Cytarabine And Venetoclax In Patients With Aml Ineligible For Intensive Chemotherapy, Andrew H Wei, Panayiotis Panayiotidis, Pau Montesinos, Kamel Laribi, Vladimir Ivanov, Inho Kim, Jan Novak, Rebecca Champion, Walter Fiedler, Maria Pagoni, Julie Bergeron, Stephen B Ting, Jing-Zhou Hou, Takahiro Yamauchi, Jianxiang Wang, Stephen A Strickland, Michael R Savona, Tara L Lin, Anoop Enjeti, Ing Soo Tiong, Sangmin Lee, Gail J Roboz, Relja Popovic, Qi Jiang, Zihuan Liu, Yan Sun, Wellington Mendes, Brenda Chyla, Courtney D Dinardo

Faculty, Staff and Student Publications

Prognostic risk categorization aids treatment selection for patients with acute myeloid leukemia (AML). Although the European LeukemiaNet (ELN) classifications (2017 and 2022) for AML have been used to stratify outcomes for patients receiving intensive chemotherapy, their application to patients receiving less intensive therapy, such as azacitidine plus venetoclax, has been less satisfactory. In response, a 4-gene classifier that stratifies older patients with AML unfit for intensive chemotherapy into those with higher benefit (wild type), intermediate benefit (FLT3-internal tandem duplication [ITD] or NRAS/KRAS mutation), or lower benefit (TP53 mutation) after azacitidine plus venetoclax treatment was developed. We hypothesized that this 4-gene …

Winner's Curse Free Robust Mendelian Randomization With Summary Data, Zhongming Xie, Wanheng Zhang, Jingshen Wang, Chong Wu

Faculty, Staff and Student Publications

In the past decade, the increased availability of genome-wide association studies summary data has popularized Mendelian Randomization (MR) for conducting causal inference. MR analyses, incorporating genetic variants as instrumental variables, are known for their robustness against reverse causation bias and unmeasured confounders. Nevertheless, classical MR analyses using summary data may still produce biased causal effect estimates due to the winner’s curse and pleiotropy issues. To address these two issues and establish valid causal conclusions, we propose a unified robust Mendelian Randomization framework with summary data, which systematically removes the winner’s curse and screens out invalid genetic instruments with pleiotropic effects. …

The Path Forward For T Cell Engagers In Patients With Prostate Cancer, Sumit K. Subudhi, Bilal A. Siddiqui, Kevin K. Zarrabi, William K. Kelly, Charles G. Drake

Department of Medical Oncology Faculty Papers

T cell engagers (TCEs) recruit T cells to the tumor microenvironment (TME) to induce antitumor immune responses. TCEs have demonstrated promising clinical responses in patients with metastatic castration-resistant prostate cancer and have advanced into phase 3 clinical trials. Here we provide an overview of the mechanisms of action of TCEs, including both CD3-targeted and CD28-targeted agents, and review the clinical development of these agents for prostate cancer. We propose a path forward for TCEs in prostate cancer, in which innovative clinical trials will facilitate a biological understanding of mechanisms of efficacy and toxicity to inform: (1) development of predictive biomarkers …

Celf1 Is A Non-Canonical Eif4e Binding Protein That Promotes Translation Of Epithelial-Mesenchymal Transition Effector Mrnas, Arindam Chaudhury, Natee Kongchan, Shebna A Massey, Rajesh Sharma, Rituraj Pal, Na Zhao, Phoebe Tsoi, Yingmin Zhu, Emuejevoke Olokpa, Sufeng Mao, Sonia Del Rincon, Lucas C Reineke, Richard E Lloyd, Marco Sardiello, Jeffrey M Rosen, Choel Kim, Josephine C Ferreon, Joel R Neilson

Faculty, Staff and Students Publications

Mounting evidence is revealing an increasing complexity of gene regulation at the level of messenger RNA (mRNA) translation. Within mammalian cells, canonical cap-dependent mRNA translation depends on the eIF4F complex, consisting of the m7G mRNA cap-binding protein eukaryotic initiation factor 4E (eIF4E), the helicase eIF4A (eIF4A), and the eIF4G (eIF4G1) scaffolding protein. eIF4G1 additionally binds poly(A) binding protein (PABPC1) to facilitate mRNA circularization and nucleates pre-translation initiation complex assembly to initiate ribosomal scanning. In breast epithelial cells, the CELF1 RNA-binding protein specifically promotes the translation of select epithelial-to-mesenchymal transition (EMT) effector mRNAs by binding GU-rich elements (GREs) within their 3' …

Novel Csf Biomarkers For Facilitating Diagnosis Of Cns-Hlh From Other Neuroinflammatory Disorders, Sharat Chandra, Kenneth D Greis, Somchai Chutipongtanate, Nathan Luebbering, Aaron Webster, Kelsey E Poisson, Kristen S Fisher, Kristi Smiley, Rebecca A Marsh, Michael B Jordan, Stella M Davies

Faculty, Staff and Students Publications

Central nervous system (CNS)-hemophagocytic lymphohistiocytosis (HLH) can mimic other neuroinflammatory disorders (ONID), often leading to misdiagnosis. Current diagnostic studies do not reliably distinguish CNS-HLH from ONID. We hypothesized that novel cerebrospinal fluid (CSF) biomarkers identified using unbiased proteomic analysis can facilitate diagnosis of CNS-HLH from ONID. Banked CSF samples were categorized into 3 groups, CNS-HLH, ONID, and controls without CNS inflammation. Proteomic analysis was performed on 25 samples per group (total N = 75). Proteins demonstrating significant changes (>1.5-fold higher and P< .05) in the CNS-HLH compared with ONID and associated with HLH pathophysiology were selected as candidate biomarkers. Cross-platform validation of candidate biomarkers, along with known biomarkers CXCL9 and osteopontin, was performed using enzyme-linked immunosorbent assay (ELISA). One hundred twenty-two proteins were identified on CSF proteomic analysis at 99% confidence. Of these, 10 proteins demonstrated a >1.5-fold change with a P< .05 in CNS-HLH compared with ONID. SerpinG1, lysozyme, and CD14 were selected as candidate biomarkers. ELISA confirmed significant elevation of all 5 biomarkers in CNS-HLH relative to ONID. Median SerpinG1 levels were1242.9 ng/mL in CNS-HLH vs 292.2 ng/mL in ONID (P ≤ .001), lysozyme 222.2 ng/mL vs 65.6 ng/mL (P = .001), and CD14 180.3 ng/mL vs 64.5 ng/mL (P ≤ .001). Median CXCL9 levels were 223.7 ng/mL in CNS-HLH vs 15.5 ng/mL in ONID (P ≤ .001), and osteopontin levels were 356.5 ng/mL vs 92.9 ng/mL (P = .001). These findings demonstrate that novel CSF biomarkers SerpinG1, lysozyme, CD14, and CXCL9 can facilitate diagnosis of CNS-HLH from ONID.

"The Only Place I Feel Understood": A Mixed Methods Survey Of Adolescent And Caregiver Perspectives On Social Media And Parental Controls, Melanie Watt Ramos, Constance M Wiemann, Lauren A Bretz

Faculty, Staff and Students Publications

Purpose

Methods

Results

Eepd1 Evolved A Unique Dna Clamping Dimer Protecting Reversed Replication Forks, Runze Shen, Altaf H Sarker, Yue Chen, Min Liu, Sunetra Roy, Andrew S Arvai, Albino Bacolla, Zamal Ahmed, Panagiotis Katsonis, Michal Hammel, Isao Kuraoka, Miaw-Sheue Tsai, Corydon Irie, Lukas Webb, Olivier Lichtarge, Chi-Lin Tsai, Susan E Tsutakawa, Katharina Schlacher, John A Tainer

Faculty, Staff and Student Publications

Exonuclease/endonuclease/phosphatase (EEP)-fold hydrolases are canonically monomeric phosphodiesterases exemplified by APE1, DNase I, and TDP2 nucleases. While EEP family domain containing protein 1 (EEPD1) acts in DNA stress responses, its proposed nuclease activities are enigmatic. Here, we integrate hybrid structural methods, evolution, biochemistry, cancer genomics, plus molecular and cell biology to define EEPD1 structure, assembly, and function at stalled DNA replication forks. Results imply EEPD1 surprisingly requires both unique EEP domain dimer and distinctive tandem Helix-hairpin-Helix [(HhH)2] domains to clamp double-stranded (ds) DNA at reversed DNA replication forks for fork protection. Small-angle X-ray Scattering (SAXS), crystal, and cryo-EM structures unveil an …