Digital Commons Network^™

Regional Analysis To Delineate Intrasample Heterogeneity With Regionalst, Yue Lyu, Chong Wu, Wei Sun, Ziyi Li

Faculty, Staff and Student Publications

MOTIVATION: Spatial transcriptomics has greatly contributed to our understanding of spatial and intra-sample heterogeneity, which could be crucial for deciphering the molecular basis of human diseases. Intra-tumor heterogeneity, e.g. may be associated with cancer treatment responses. However, the lack of computational tools for exploiting cross-regional information and the limited spatial resolution of current technologies present major obstacles to elucidating tissue heterogeneity.

RESULTS: To address these challenges, we introduce RegionalST, an efficient computational method that enables users to quantify cell type mixture and interactions, identify sub-regions of interest, and perform cross-region cell type-specific differential analysis for the first time. Our simulations …

Gut Microbiota And Blood Metabolites Related To Fiber Intake And Type 2 Diabetes, Zheng Wang, Brandilyn A Peters, Bing Yu, Megan L Grove, Tao Wang, Xiaonan Xue, Bharat Thyagarajan, Martha L Daviglus, Eric Boerwinkle, Gang Hu, Yasmin Mossavar-Rahmani, Carmen R Isasi, Rob Knight, Robert D Burk, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

BACKGROUND: Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D).

METHODS: This study included up to 11 394 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Diet was assessed with two 24-hour dietary recalls at baseline. We examined associations of dietary fiber intake with gut microbiome measured by shotgun metagenomics (350 species/85 genera and 1958 enzymes; n=2992 at …

Cancer Biomarkers: Emerging Trends And Clinical Implications For Personalized Treatment, Antonio Passaro, Maise Al Bakir, Emily G Hamilton, Maximilian Diehn, Fabrice André, Sinchita Roy-Chowdhuri, Giannis Mountzios, Ignacio I Wistuba, Charles Swanton, Solange Peters

Faculty, Staff and Student Publications

The integration of cancer biomarkers into oncology has revolutionized cancer treatment, yielding remarkable advancements in cancer therapeutics and the prognosis of cancer patients. The development of personalized medicine represents a turning point and a new paradigm in cancer management, as biomarkers enable oncologists to tailor treatments based on the unique molecular profile of each patient's tumor. In this review, we discuss the scientific milestones of cancer biomarkers and explore future possibilities to improve the management of patients with solid tumors. This progress is primarily attributed to the biological characterization of cancers, advancements in testing methodologies, elucidation of the immune microenvironment, …

Association Of Nightly Fasting, Meal Frequency, And Skipping Meals With Metabolic Syndrome Among Kuwaiti Adults, Fatema Alkhulaifi, Suad Al-Hooti, Sameer Al-Zenki, Husam Alomirah, Qian Xiao, Wenyaw Chan, Fuqing Wu, Charles Darkoh

Faculty, Staff and Student Publications

Mounting evidence suggests that meal timing and frequency are associated with cardiometabolic health by influencing circadian rhythms. However, the evidence is inconsistent and limited, especially in non-Western cultures. This cross-sectional study aims to investigate the association between temporal habits of dietary intake, such as nightly fasting duration and meal frequency, and metabolic syndrome among Kuwaiti adults. A 24-hour recall was used to assess temporal habits of dietary intake. Meal frequency was defined as the number of daily eating episodes. The study included a total of 757 adults aged 20 years and older. The participants' mean age was 37.8 ± 12.3 …

Telehealth Evaluation In The United States: Protocol For A Scoping Review, Yunxi Zhang, Yueh-Yun Lin, Lincy S Lal, Jennifer C Reneker, Elizabeth G Hinton, Saurabh Chandra, J Michael Swint

Faculty, Staff and Student Publications

BACKGROUND: The rapid expansion of telehealth services, driven by the COVID-19 pandemic, necessitates systematic evaluation to guarantee the quality, effectiveness, and cost-effectiveness of telehealth services and programs in the United States. While numerous evaluation frameworks have emerged, crafted by various stakeholders, their comprehensiveness is limited, and the overall state of telehealth evaluation remains unclear.

OBJECTIVE: The overarching goal of this scoping review is to create a comprehensive overview of telehealth evaluation, incorporating perspectives from multiple stakeholder categories. Specifically, we aim to (1) map the existing landscape of telehealth evaluation, (2) identify key concepts for evaluation, (3) synthesize existing evaluation frameworks, …

Sans-Cnn: An Automated Machine Learning Technique For Spaceflight Associated Neuro-Ocular Syndrome With Astronaut Imaging Data, Sharif Amit Kamran, Khondker Fariha Hossain, Joshua Ong, Nasif Zaman, Ethan Waisberg, Phani Paladugu, Andrew G Lee, Alireza Tavakkoli

Faculty, Staff and Student Publications

Spaceflight associated neuro-ocular syndrome (SANS) is one of the largest physiologic barriers to spaceflight and requires evaluation and mitigation for future planetary missions. As the spaceflight environment is a clinically limited environment, the purpose of this research is to provide automated, early detection and prognosis of SANS with a machine learning model trained and validated on astronaut SANS optical coherence tomography (OCT) images. In this study, we present a lightweight convolutional neural network (CNN) incorporating an EfficientNet encoder for detecting SANS from OCT images titled "SANS-CNN." We used 6303 OCT B-scan images for training/validation (80%/20% split) and 945 for testing …

Gpr56 In Gvl: Marker Or Mechanism?, Audra N Iness, Pavan Bachireddy

Faculty, Staff and Student Publications

No abstract provided.

Embracing Cancer Complexity: Hallmarks Of Systemic Disease, Charles Swanton, Elsa Bernard, Chris Abbosh, Fabrice André, Johan Auwerx, Allan Balmain, Dafna Bar-Sagi, René Bernards, Susan Bullman, James Degregori, Catherine Elliott, Ayelet Erez, Gerard Evan, Mark A Febbraio, Andrés Hidalgo, Mariam Jamal-Hanjani, Johanna A Joyce, Matthew Kaiser, Katja Lamia, Jason W Locasale, Sherene Loi, Ilaria Malanchi, Miriam Merad, Kathryn Musgrave, Ketan J Patel, Sergio Quezada, Jennifer A Wargo, Ashani Weeraratna, Eileen White, Frank Winkler, John N Wood, Karen H Vousden, Douglas Hanahan

Faculty, Staff and Student Publications

The last 50 years have witnessed extraordinary developments in understanding mechanisms of carcinogenesis, synthesized as the hallmarks of cancer. Despite this logical framework, our understanding of the molecular basis of systemic manifestations and the underlying causes of cancer-related death remains incomplete. Looking forward, elucidating how tumors interact with distant organs and how multifaceted environmental and physiological parameters impinge on tumors and their hosts will be crucial for advances in preventing and more effectively treating human cancers. In this perspective, we discuss complexities of cancer as a systemic disease, including tumor initiation and promotion, tumor micro- and immune macro-environments, aging, metabolism …

School Teachers' Perceptions Of Adolescent Human Papillomavirus (Hpv) Vaccination: A Systematic Review, Jihye Choi, Efrat K Gabay, Paula M Cuccaro

Faculty, Staff and Student Publications

School nurses are uniquely positioned to educate students about immunizations, including human papillomavirus (HPV) vaccination, but schools are often without a nurse for different reasons. In lieu of nurses, teachers who closely interact with students and are traditionally well-trusted by parents may be able to communicate about HPV vaccination, alleviating parental vaccine hesitancy. This systematic review explores school teachers' perspectives on adolescent HPV vaccination and factors influencing their willingness to make vaccine recommendations. We searched three databases with appropriate medical subject headings and keywords to identify relevant studies. We reviewed fifteen studies and provided an extensive summary and a comparison …

Case Weighted Power Priors For Hybrid Control Analyses With Time-To-Event Data, Evan Kwiatkowski, Jiawen Zhu, Xiao Li, Herbert Pang, Grazyna Lieberman, Matthew A Psioda

Faculty, Staff and Student Publications

We develop a method for hybrid analyses that uses external controls to augment internal control arms in randomized controlled trials (RCTs) where the degree of borrowing is determined based on similarity between RCT and external control patients to account for systematic differences (e.g., unmeasured confounders). The method represents a novel extension of the power prior where discounting weights are computed separately for each external control based on compatibility with the randomized control data. The discounting weights are determined using the predictive distribution for the external controls derived via the posterior distribution for time-to-event parameters estimated from the RCT. This method …

Exploring The Prospects Of Transcranial Electrical Stimulation (Tes) As A Therapeutic Intervention For Post-Stroke Motor Recovery: A Narrative Review, Hao Meng, Michael Houston, Yingchun Zhang, Sheng Li

Faculty, Staff and Student Publications

Introduction: Stroke survivors often have motor impairments and related functional deficits. Transcranial Electrical Stimulation (tES) is a rapidly evolving field that offers a wide range of capabilities for modulating brain function, and it is safe and inexpensive. It has the potential for widespread use for post-stroke motor recovery. Transcranial Direct Current Stimulation (tDCS), Transcranial Alternating Current Stimulation (tACS), and Transcranial Random Noise Stimulation (tRNS) are three recognized tES techniques that have gained substantial attention in recent years but have different mechanisms of action. tDCS has been widely used in stroke motor rehabilitation, while applications of tACS and tRNS are very …

An Analysis Of Conventional And Modern Packaging Approaches For Cut Flowers: A Review Article, Nahed M Rashed, Saba Ambreen Memon, Saleh M Al Turki, Tarek A Shalaby, Mohamed M El-Mogy

Faculty, Staff and Student Publications

Fresh-cut flowers are considered to be one of the most delicate and challenging commercial crops. It is important to take into consideration how to minimize loss during storage and transportation when preserving cut flowers. Many impinging (bad effect) forces can interact to shorten the flowers' vase life. In the flower industry, effective methods need to be developed to extend freshly cut flowers' life. Fresh-cut flowers' vase life can be shortened by a variety of interlocking causes. The flower industry must develop new techniques to extend the flowers' vase lifespan. This review provides comprehensive, up-to-date information on classical, modified atmosphere packaging …

Reinforced Tissue Matrix To Strengthen The Abdominal Wall Following Reversal Of Temporary Ostomies Or To Treat Incisional Hernias, Spencer P Lake, Corey R Deeken, Amit K Agarwal

Faculty, Staff and Student Publications

BACKGROUND: Abdominal wall deficiencies or weakness are a common complication of temporary ostomies, and incisional hernias frequently develop after colostomy or ileostomy takedown. The use of synthetic meshes to reinforce the abdominal wall has reduced hernia occurrence. Biologic meshes have also been used to enhance healing, particularly in contaminated conditions. Reinforced tissue matrices (RTMs), which include a biologic scaffold of native extracellular matrix and a synthetic component for added strength/durability, are designed to take advantage of aspects of both synthetic and biologic materials. To date, RTMs have not been reported to reinforce the abdominal wall following stoma reversal.

AIM: To …

High-Density Glass Scintillators For Proton Radiography-Relative Luminosity, Proton Response, And Spatial Resolution, Ethan Stolen, Ryan Fullarton, Rain Hein, Robin L Conner, Luiz G Jacobsohn, Charles-Antoine Collins-Fekete, Sam Beddar, Ugur Akgun, Daniel Robertson

Faculty, Staff and Student Publications

Proton radiography is a promising development in proton therapy, and researchers are currently exploring optimal detector materials to construct proton radiography detector arrays. High-density glass scintillators may improve integrating-mode proton radiography detectors by increasing spatial resolution and decreasing detector thickness. We evaluated several new scintillators, activated with europium or terbium, with proton response measurements and Monte Carlo simulations, characterizing relative luminosity, ionization quenching, and proton radiograph spatial resolution. We applied a correction based on Birks's analytical model for ionization quenching. The data demonstrate increased relative luminosity with increased activation element concentration, and higher relative luminosity for samples activated with europium. …

Raf Inhibitor Re-Challenge Therapy In Braf-Aberrant Pan-Cancers: The Re-Raffle Study, Blessie Elizabeth Nelson, Jason Roszik, Jibran Ahmed, Carmelia Maria Noia Barretto, Mirella Nardo, Erick Campbell, Amber M Johnson, Sarina A Piha-Paul, Isabella C Glitza Oliva, Shiao-Pei Weathers, Maria Cabanillas, Milind Javle, Funda Meric-Bernstam, Vivek Subbiah

Faculty, Staff and Student Publications

Previous studies have shown the clinical benefit of rechallenging the RAF pathway in melanoma patients previously treated with BRAF inhibitors. 44 patients with multiple tumors harboring RAF alterations were rechallenged with a second RAF inhibitor, either as monotherapy or in combination with other therapies, after prior therapy with a first RAF inhibitor. This retrospective observational study results showed that rechallenging with RAFi(s) led to an overall response rate of 18.1% [PR in thyroid (1 anaplastic; 3 papillary), 1 ovarian, 2 melanoma, 1 cholangiocarcinoma, and 1 anaplastic astrocytoma]. The clinical benefit rate was 54.5%; more than 30% of patients had durable …

Amino Acid Formula Induces Microbiota Dysbiosis And Depressive-Like Behavior In Mice, Ji Hu, Kaixin He, Yifei Yang, Chuan Huang, Yiping Dou, Hao Wang, Guorong Zhang, Jingyuan Wang, Chaoshi Niu, Guoqiang Bi, Lan Zhang, Shu Zhu

Faculty, Staff and Student Publications

Amino acid formula (AAF) is increasingly consumed in infants with cow's milk protein allergy; however, the long-term influences on health are less described. In this study, we established a mouse model by subjecting neonatal mice to an amino acid diet (AAD) to mimic the feeding regimen of infants on AAF. Surprisingly, AAD-fed mice exhibited dysbiotic microbiota and increased neuronal activity in both the intestine and brain, as well as gastrointestinal peristalsis disorders and depressive-like behavior. Furthermore, fecal microbiota transplantation from AAD-fed mice or AAF-fed infants to recipient mice led to elevated neuronal activations and exacerbated depressive-like behaviors compared to that …

Correction: The Novel Phosphatase Nudt5 Is A Critical Regulator Of Triple-Negative Breast Cancer Growth, Jing Qian, Yanxia Ma, William M Tahaney, Cassandra L Moyer, Amanda Lanier, Jamal Hill, Darian Coleman, Negar Koupaei, Susan G Hilsenbeck, Michelle I Savage, Brent D G Page, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

No abstract provided.

Effect Of Early Vs Late Inguinal Hernia Repair On Serious Adverse Event Rates In Preterm Infants: A Randomized Clinical Trial, Martin L Blakely, Andrea Krzyzaniak, Melvin S Dassinger, Claudia Pedroza, Jorn-Hendrik Weitkamp, Ankush Gosain, Michael Cotten, Susan R Hintz, Henry Rice, Sherry E Courtney, Kevin P Lally, Namasivayam Ambalavanan, Catherine M Bendel, Kim Chi T Bui, Casey Calkins, Nicole M Chandler, Roshni Dasgupta, Jonathan M Davis, Katherine Deans, Daniel A Deugarte, Jeffrey Gander, Carl-Christian A Jackson, Martin Keszler, Karen Kling, Stephen J Fenton, Kimberley A Fisher, Tyler Hartman, Eunice Y Huang, Saleem Islam, Frances Koch, Shabnam Lainwala, Aaron Lesher, Monica Lopez, Meghna Misra, Jamie Overbey, Brenda Poindexter, Robert Russell, Steven Stylianos, Douglas Y Tamura, Bradley A Yoder, Donald Lucas, Donald Shaul, P Ben Ham, Colleen Fitzpatrick, Kara Calkins, Aaron Garrison, Diomel De La Cruz, Shahab Abdessalam, Charlotte Kvasnovsky, Bradley J Segura, Joel Shilyansky, Lynne M Smith, Jon E Tyson

Faculty, Staff and Student Publications

Importance: Inguinal hernia repair in preterm infants is common and is associated with considerable morbidity. Whether the inguinal hernia should be repaired prior to or after discharge from the neonatal intensive care unit is controversial.

Objective: To evaluate the safety of early vs late surgical repair for preterm infants with an inguinal hernia.

Design, setting, and participants: A multicenter randomized clinical trial including preterm infants with inguinal hernia diagnosed during initial hospitalization was conducted between September 2013 and April 2021 at 39 US hospitals. Follow-up was completed on January 3, 2023.

Interventions: In the early repair strategy, infants underwent inguinal …

Author Correction: Cytoskeleton Remodeling Induced By Smyd2 Methyltransferase Drives Breast Cancer Metastasis, Alexandre G Casanova, Gael S Roth, Simone Hausmann, Xiaoyin Lu, Ludivine J M Bischoff, Emilie M Froeliger, Lucid Belmudes, Ekaterina Bourova-Flin, Natasha M Flores, Ana Morales Benitez, Tourkian Chasan, Marcello Caporicci, Jessica Vayr, Sandrine Blanchet, Francesco Ielasi, Sophie Rousseaux, Pierre Hainaut, Or Gozani, Muriel Le Romancer, Yohann Couté, Andres Palencia, Pawel K Mazur, Nicolas Reynoird

Faculty, Staff and Student Publications

No abstract provided.

Integration Of Kupffer Cells Into Human Ipsc-Derived Liver Organoids For Modeling Liver Dysfunction In Sepsis, Yang Li, Yunzhong Nie, Xia Yang, Yang Liu, Xiaoshan Deng, Yoshihito Hayashi, Riana Plummer, Qinglin Li, Na Luo, Toshiharu Kasai, Takashi Okumura, Yu Kamishibahara, Takemasa Komoto, Takuya Ohkuma, Satoshi Okamoto, Yumiko Isobe, Kiyoshi Yamaguchi, Yoichi Furukawa, Hideki Taniguchi

Faculty, Staff and Student Publications

Maximizing the potential of human liver organoids (LOs) for modeling human septic liver requires the integration of innate immune cells, particularly resident macrophage Kupffer cells. In this study, we present a strategy to generate LOs containing Kupffer cells (KuLOs) by recapitulating fetal liver hematopoiesis using human induced pluripotent stem cell (hiPSC)-derived erythro-myeloid progenitors (EMPs), the origin of tissue-resident macrophages, and hiPSC-derived LOs. Remarkably, LOs actively promote EMP hematopoiesis toward myeloid and erythroid lineages. Moreover, supplementing with macrophage colony-stimulating factor (M-CSF) proves crucial in sustaining the hematopoietic population during the establishment of KuLOs. Exposing KuLOs to sepsis-like endotoxins leads to significant …

A Novel Machine Learning Algorithm Selects Proteome Signature To Specifically Identify Cancer Exosomes, Bingrui Li, Fernanda G Kugeratski, Raghu Kalluri

Faculty, Staff and Student Publications

Non-invasive early cancer diagnosis remains challenging due to the low sensitivity and specificity of current diagnostic approaches. Exosomes are membrane-bound nanovesicles secreted by all cells that contain DNA, RNA, and proteins that are representative of the parent cells. This property, along with the abundance of exosomes in biological fluids makes them compelling candidates as biomarkers. However, a rapid and flexible exosome-based diagnostic method to distinguish human cancers across cancer types in diverse biological fluids is yet to be defined. Here, we describe a novel machine learning-based computational method to distinguish cancers using a panel of proteins associated with exosomes. Employing …

The Genomic And Evolutionary Landscapes Of Anaplastic Thyroid Carcinoma, Peter Y F Zeng, Stephenie D Prokopec, Stephen Y Lai, Nicole Pinto, Michelle A Chan-Seng-Yue, Roderick Clifton-Bligh, Michelle D Williams, Christopher J Howlett, Paul Plantinga, Matthew J Cecchini, Alfred K Lam, Iram Siddiqui, Jianxin Wang, Ren X Sun, John D Watson, Reju Korah, Tobias Carling, Nishant Agrawal, Nicole Cipriani, Douglas Ball, Barry Nelkin, Lisa M Rooper, Justin A Bishop, Cathie Garnis, Ken Berean, Norman G Nicolson, Paul Weinberger, Ying C Henderson, Christopher M Lalansingh, Mao Tian, Takafumi N Yamaguchi, Julie Livingstone, Adriana Salcedo, Krupal Patel, Frederick Vizeacoumar, Alessandro Datti, Liu Xi, Yuri E Nikiforov, Robert Smallridge, John A Copland, Laura A Marlow, Martin D Hyrcza, Leigh Delbridge, Stan Sidhu, Mark Sywak, Bruce Robinson, Kevin Fung, Farhad Ghasemi, Keith Kwan, S Danielle Macneil, Adrian Mendez, David A Palma, Mohammed I Khan, Mushfiq Shaikh, Kara M Ruicci, Bret Wehrli, Eric Winquist, John Yoo, Joe S Mymryk, James W Rocco, David Wheeler, Steve Scherer, Thomas J Giordano, John W Barrett, William C Faquin, Anthony J Gill, Gary Clayman, Paul C Boutros, Anthony C Nichols

Faculty, Staff and Student Publications

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid …

Identification Of Nonfunctional Alternatively Spliced Isoforms Of Sting In Human Acute Myeloid Leukemia, Akash R Boda, Arthur J Liu, Susana Castro-Pando, Benjamin T Whitfield, Jeffrey J Molldrem, Gheath Al-Atrash, Maria Emilia Di Francesco, Philip Jones, Casey R Ager, Michael A Curran

Faculty, Staff and Student Publications

UNLABELLED: Lack of robust activation of Stimulator of Interferon Genes (STING) pathway and subsequent induction of type I IFN responses is considered a barrier to antitumor immunity in acute myeloid leukemia (AML). Using common human AML cell lines as in vitro tools to evaluate the efficacy of novel STING agonists, we found most AML lines to be poor producers of IFNs upon exposure to extremely potent agonists, suggesting cell-intrinsic suppression of STING signaling may occur. We observed unexpected patterns of response that did not correlate with levels of STING pathway components or of known enzymes associated with resistance. To identify …

Dopamine Lesions Alter The Striatal Encoding Of Single-Limb Gait, Long Yang, Deepak Singla, Alexander K Wu, Katy A Cross, Sotiris C Masmanidis

Faculty, Staff and Student Publications

The striatum serves an important role in motor control, and neurons in this area encode the body's initiation, cessation, and speed of locomotion. However, it remains unclear whether the same neurons also encode the step-by-step rhythmic motor patterns of individual limbs that characterize gait. By combining high-speed video tracking, electrophysiology, and optogenetic tagging, we found that a sizable population of both D1 and D2 receptor expressing medium spiny projection neurons (MSNs) were phase-locked to the gait cycle of individual limbs in mice. Healthy animals showed balanced limb phase-locking between D1 and D2 MSNs, while dopamine depletion led to stronger phase-locking …

Extend The Benchmarking Indel Set By Manual Review Using The Individual Cell Line Sequencing Data From The Sequencing Quality Control 2 (Seqc2) Project, Binsheng Gong, Dan Li, Yifan Zhang, Rebecca Kusko, Samir Lababidi, Zehui Cao, Mingyang Chen, Ning Chen, Qiaochu Chen, Qingwang Chen, Jiacheng Dai, Qiang Gan, Yuechen Gao, Mingkun Guo, Gunjan Hariani, Yujie He, Wanwan Hou, He Jiang, Garima Kushwaha, Jian-Liang Li, Jianying Li, Yulan Li, Liang-Chun Liu, Ruimei Liu, Shiming Liu, Edwin Meriaux, Mengqing Mo, Mathew Moore, Tyler J Moss, Quanne Niu, Ananddeep Patel, Luyao Ren, Nedda F Saremi, Erfei Shang, Jun Shang, Ping Song, Siqi Sun, Brent J Urban, Danke Wang, Shangzi Wang, Zhining Wen, Xiangyi Xiong, Jingcheng Yang, Lihui Yin, Chao Zhang, Ruolan Zhang, Ambica Bhandari, Wanshi Cai, Agda Karina Eterovic, Dalila B Megherbi, Tieliu Shi, Chen Suo, Ying Yu, Yuanting Zheng, Natalia Novoradovskaya, Renee L Sears, Leming Shi, Wendell Jones, Weida Tong, Joshua Xu

Faculty, Staff and Student Publications

Accurate indel calling plays an important role in precision medicine. A benchmarking indel set is essential for thoroughly evaluating the indel calling performance of bioinformatics pipelines. A reference sample with a set of known-positive variants was developed in the FDA-led Sequencing Quality Control Phase 2 (SEQC2) project, but the known indels in the known-positive set were limited. This project sought to provide an enriched set of known indels that would be more translationally relevant by focusing on additional cancer related regions. A thorough manual review process completed by 42 reviewers, two advisors, and a judging panel of three researchers significantly …

Advancing Primary Ciliary Dyskinesia Diagnosis Through High-Speed Video Microscopy Analysis, Wilfredo De Jesús-Rojas, Zachary J Demetriou, José Muñiz-Hernández, Gabriel Rosario-Ortiz, Frances M Quiñones, Marcos J Ramos-Benitez, Ricardo A Mosquera

Faculty, Staff and Student Publications

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite 70% of Puerto Rican patients having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency …

Digital Twins For Health: A Scoping Review, Evangelia Katsoulakis, Qi Wang, Huanmei Wu, Leili Shahriyari, Richard Fletcher, Jinwei Liu, Luke Achenie, Hongfang Liu, Pamela Jackson, Ying Xiao, Tanveer Syeda-Mahmood, Richard Tuli, Jun Deng

Faculty, Staff and Student Publications

The use of digital twins (DTs) has proliferated across various fields and industries, with a recent surge in the healthcare sector. The concept of digital twin for health (DT4H) holds great promise to revolutionize the entire healthcare system, including management and delivery, disease treatment and prevention, and health well-being maintenance, ultimately improving human life. The rapid growth of big data and continuous advancement in data science (DS) and artificial intelligence (AI) have the potential to significantly expedite DT research and development by providing scientific expertise, essential data, and robust cybertechnology infrastructure. Although various DT initiatives have been underway in the …

Tumor Treating Fields Suppress Tumor Cell Growth And Neurologic Decline In Models Of Spinal Metastases, Daniel Ledbetter, Romulo Augusto Andrade De Almeida, Xizi Wu, Ariel Naveh, Chirag B Patel, Queena Gonzalez, Thomas H Beckham, Robert North, Laurence Rhines, Jing Li, Amol Ghia, David Aten, Claudio Tatsui, Christopher Alvarez-Breckenridge

Faculty, Staff and Student Publications

Spinal metastases can result in severe neurologic compromise and decreased overall survival. Despite treatment advances, local disease progression is frequent, highlighting the need for novel therapies. Tumor treating fields (TTFields) impair tumor cell replication and are influenced by properties of surrounding tissue. We hypothesized that bone's dielectric properties will enhance TTFields-mediated suppression of tumor growth in spinal metastasis models. Computational modeling of TTFields intensity was performed following surgical resection of a spinal metastasis and demonstrated enhanced TTFields intensity within the resected vertebral body. Additionally, luciferase-tagged human KRIB osteosarcoma and A549 lung adenocarcinoma cell lines were cultured in demineralized bone grafts …

Pilot Study To Assess The Effectiveness Of The Sustainable Culturally Adaptive Nutrition Program (Scan) To Improve Adherence To The National Diabetes Prevention Program, William B Perkison, Pierre Fwelo, Fernanda Velasco-Huerta, Natalia I Heredia, James J Yang, Sidra S Beg, Belinda M Reininger, Serena A Rodriguez, Maha Almohamad, Catherine Pulicken, Ella Garza, Grace E White, Maria E Fernandez

Faculty, Staff and Student Publications

PURPOSE: The Sustainable Culturally Adapted Nutrition Program (SCAN) is a novel adaptation to the National Diabetes Prevention Program (NDPP) that aims to improve attendance and effectiveness. This paper presents its feasibility and impact through the initial 6-month outcomes.

DESIGN: A pragmatic quasi-experimental pilot study with intervention (DPP plus SCAN) and control (DPP only) groups.

SAMPLES AND INCLUSION CRITERIA: Sustainable Culturally Adapted Nutrition Program participants were recruited from federally qualified health center (FQHC) clinic patients enrolled in a NDPP in Houston, Texas. Participants needed to be (1) ≥18 years old, (2) body mass index >25, (3) no prior diagnosis of diabetes, …

Intrathecal Gene Therapy For Giant Axonal Neuropathy, Diana X Bharucha-Goebel, Joshua J Todd, Dimah Saade, Gina Norato, Minal Jain, Tanya Lehky, Rachel M Bailey, Jessica A Chichester, Roberto Calcedo, Diane Armao, A Reghan Foley, Payam Mohassel, Eshetu Tesfaye, Bradley P Carlin, Beth Seremula, Melissa Waite, Wadih M Zein, Laryssa A Huryn, Thomas O Crawford, Charlotte J Sumner, Ahmet Hoke, John D Heiss, Lawrence Charnas, Jody E Hooper, Thomas W Bouldin, Elizabeth M Kang, Denis Rybin, Steven J Gray, Carsten G Bönnemann

Faculty, Staff and Student Publications

Background: Giant axonal neuropathy is a rare, autosomal recessive, pediatric, polysymptomatic, neurodegenerative disorder caused by biallelic loss-of-function variants in GAN, the gene encoding gigaxonin.

Methods: We conducted an intrathecal dose-escalation study of scAAV9/JeT-GAN (a self-complementary adeno-associated virus-based gene therapy containing the GAN transgene) in children with giant axonal neuropathy. Safety was the primary end point. The key secondary clinical end point was at least a 95% posterior probability of slowing the rate of change (i.e., slope) in the 32-item Motor Function Measure total percent score at 1 year after treatment, as compared with the pretreatment slope.

Results: One of …