Genetic Phenomena Commons^™

Reviewing Vascular Influences On Neuronal Migration, Cortical Development, And Neurodevelopmental Disorders: Focus On Autism, Adhd And Schizophrenia, Lalit K Ahirwar, Spiros L Blackburn, Devin W Mcbride, Peeyush Kumar T

Faculty, Staff and Student Publications

During cortical development, newly born neurons migrate radially or tangentially from their origin to expand the cortex. Simultaneously, neuron-derived factors support angiogenesis, and an elaborate network of blood cerebral vessels develops in the cortex. Traditionally, blood cerebral vessels were considered to support the growing cortex or migrating neurons by providing nutrients and oxygen. However, recent studies have shed light on Endothelial cells' influence on cortical development; they guide neuronal migration by providing molecular cues and structural support. Here, we review the current understanding of how CNS cerebral vessels support neurogenesis, neuronal migration, and the formation of the six-layer cortical structure …

Relative Biological Effectiveness-Clinical Practice At Us Proton Therapy Centers, Armin Lühr, Radhe Mohan, Anita Mahajan, Helen A Shih, Harald Paganetti

Faculty, Staff and Student Publications

Purpose: Proton therapy, with its high conformality and superior dose distribution, is becoming an increasingly prevalent modality in radiation oncology. Although a generic relative biological effectiveness (RBE) value of 1.1 for treatment planning has been adopted, evidence suggests that RBE varies with dose, linear energy transfer (LET), and biological endpoints. This variation raises concerns about underestimating the RBE-weighted dose, which may significantly impact treatment outcomes. To assess the awareness and management of RBE variability in clinical practice, we conducted a survey among US proton therapy centers.

Materials and methods: The survey consisted of 32 questions grouped into subtopics, such as …

Impact Of Postpartum Diagnosis On Survival Of Women With Inflammatory Breast Cancer, Jennifer H Chen, Rebecca S Slack Tidwell, Megumi Kai, Anthony Lucci, Wendy A Woodward, Helen M Johnson

Faculty, Staff and Student Publications

Background: Postpartum diagnosis of breast cancer confers increased risk of metastasis and death, possibly because of protumorigenic pathways that occur after weaning. We sought to evaluate the impact of postpartum diagnosis on survival in patients with inflammatory breast cancer (IBC).

Methods: We performed a retrospective analysis of patients with nonmetastatic IBC enrolled in a prospective registry (2007-2023). Kruskal-Wallis, χ2, and Fisher exact tests were used to compare between postpartum groups. The Kaplan-Meier method and log-rank tests were used for survival estimates.

Results: Among 320 patients with IBC, 25 (7.8%) were nulliparous, 31 (9.7%) were 0 to 5 years postpartum, 26 …

Bayesian Prediction Of Event Times Using Mixture Model For Blinded Randomized Controlled Trials, Jingyan Fu, Dan Zhao, Donia Skanji, Hua Liu, Rui Sammi Tang, Ying Yuan

Faculty, Staff and Student Publications

Accurate prediction of key milestone dates, such as the timing of interim and final analyses, is crucial in event-driven clinical trials with time-to-event endpoints. These predictions facilitate timely decision-making, enhance strategic planning and optimize resource allocation while minimizing patient exposure to potentially ineffective or harmful therapies. Existing methods for predicting event timing in blinded randomized clinical trials (RCTs) typically assume identical time-to-event distributions for the treatment and control arms, implying no treatment effect. This assumption fails when the treatment is more effective than the control, which is often the very outcome the trial seeks to detect, leading to biased predictions. …

Individualizing Nsaid Therapy In Axial Spondyloarthritis: N-Of-1 Trials With Bayesian Analysis, Mark C Hwang, Seokhun Kim, Shervin Assassi, Reyna Chavez, Joyce Samuel, Charles Green, Jon Tyson, John Reveille

Faculty, Staff and Student Publications

Objective: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the spine and sacroiliac joints. NSAIDs are first-line therapy, but individual responses vary widely. We evaluated the efficacy and patient preference of three NSAIDs (celecoxib, meloxicam and naproxen) through Bayesian N-of-1 clinical trials to optimize axSpA management.

Methods: We conducted N-of-1 trials with 42 patients meeting ASAS criteria for axSpA. Each patient was asked to complete two cycles of randomized double-blind crossover comparisons of the three NSAIDs, each for 4 weeks. The primary end point was the change in the Ankylosing Spondylitis Disease Activity Score (ASDAS). Bayesian analysis assessed …

Research Hotspots And Trends In The Field Of Immune Checkpoint Inhibitors (Icis) For Cervical Cancer: A Bibliometric Study From 2014 To 2024, Chaoyan Shen, Juan Zhang, Guanyu Zhang, Hao Luo, Shuangke Zhang, Quan Yuan, Wei Xu, Wei Wang, Lele Miao

Faculty, Staff and Student Publications

In recent years, immune checkpoint inhibitors (ICIs) have emerged as a novel immunotherapeutic approach, offering renewed hope for enhancing cervical cancer patient prognosis. This study represents the inaugural bibliometric analysis of ICIs in the context of cervical cancer, covering the period from 2014 to 2024. A total of 422 articles were identified through the Web of Science Core Collection database, amassing 10,977 citations, with a consistent annual increase in the number of publications. The leading contributors in terms of countries, institutions, journals, and authors included China, the University of Texas System, Frontiers in Oncology, and Bradley J. Monk, respectively. …

Improvement And Maintenance Of Clinical Outcome Assessments In Atopic Dermatitis With Amlitelimab, Andrew Blauvelt, Raj Chovatiya, Joseph F Merola, Stephan Weidinger, Ken Igawa, Ella Brookes, Christine Weber, Jennifer Wang, Cori Gray

Faculty, Staff and Student Publications

Background: Amlitelimab, a fully human, nondepleting, anti-OX40 ligand monoclonal antibody, demonstrated reductions in lesional and pruritic endpoints in adults with moderate-to-severe atopic dermatitis (AD) in phase 2a and 2b trials.

Objectives: Here, we examined the effect and durability of amlitelimab on clinical outcome assessments (COAs) in the randomized STREAM-AD phase 2b trial.

Methods: Adults with moderate-to-severe AD with prior inadequate response to or inadvisability of topical medications received subcutaneous amlitelimab (250 mg with 500-mg loading dose, 250 mg, 125 mg or 62.5 mg) or placebo every 4 weeks in Part 1 (Weeks 0-24; 1:1:1:1:1 randomization). In Part 2, Week 24 …

The Longitudinal Impact Of Radiotherapy On Osseointegrated Hearing Aid Outcomes And Complications, Benjamin D Lovin, Mike Hernandez, Paul W Gidley, Karine Al Feghali, Jack Phan, Catherine Wang, Congjun Wang, Dianna Roberts, Marc-Elie Nader

Faculty, Staff and Student Publications

Objective: To evaluate the impact of radiotherapy on osseointegrated hearing aids (OIHA) complications.

Methods: Retrospective review of percutaneous OIHA performed from 2006 to 2021 at an academic institution. Implant and abutment-related complications were evaluated and stratified by radiation parameters. Main outcome measures were abutment, implant, and major complications assessed using the modified Holgers and IPS grading scales.

Results: Total of 190 OIHA were included; 124 (65%) were placed in bones that previously or subsequently received radiation. Total of 84 (44%) OIHA experienced at least one complication at mean 43.3 months. Radiation cohort had greater rates of having any complication (p …

Smart Spatial Omics (S2-Omics) Optimizes Region Of Interest Selection To Capture Molecular Heterogeneity In Diverse Tissues, Musu Yuan, Kaitian Jin, Hanying Yan, Amelia Schroeder, Chunyu Luo, Sicong Yao, Bernhard Dumoulin, Jonathan Levinsohn, Tianhao Luo, Jean R Clemenceau, Inyeop Jang, Minji Kim, Yunhe Liu, Minghua Deng, Emma E Furth, Parker Wilson, Anupma Nayak, Idania Lubo, Luisa Maren Solis Soto, Linghua Wang, Jeong Hwan Park, Katalin Susztak, Tae Hyun Hwang, Mingyao Li

Faculty, Staff and Student Publications

Spatial omics technologies have transformed biomedical research by enabling high-resolution molecular profiling while preserving the native tissue architecture. These advances provide unprecedented insights into tissue structure and function. However, the high cost and time-intensive nature of spatial omics experiments necessitate careful experimental design, particularly in selecting regions of interest (ROIs) from large tissue sections. Currently, ROI selection is performed manually, which introduces subjectivity, inconsistency and a lack of reproducibility. Previous studies have shown strong correlations between spatial molecular patterns and histological features, suggesting that readily available and cost-effective histology images can be leveraged to guide spatial omics experiments. Here we …

The Deubiquitinating Enzyme Cezanne Stabilizes Brca1 By Counteracting Apc/C And Ube2s-Dependent Lys11-Linked Ubiquitination, Longqiang Wang, Xiao Wu, Atanu Paul, Jun Yao, Bin Wang

Faculty, Staff and Student Publications

The breast and ovarian tumor suppressor BRCA1 is a cell cycle-regulated protein and tumors with reduced BRCA1 protein level may share molecular features of BRCA1-mutant tumor and respond to PARPi therapy. Here, we identify that BRCA1 protein stability is controlled through ubiquitin lysine 11 (K11)-linkage modification under the regulation of Cezanne deubiquitinating enzyme, APC/C E3 ligase, and Ube2S E2 conjugating enzyme in a cell cycle-dependent manner. Cezanne-deficiency leads to increased BRCA1 K11-ubiquitination, decreased BRCA1 protein level, and increased cellular sensitivity to PARPi. The BRCA1 K11-linked ubiquitination is carried out through a degron on BRCA1 that is recognized by APC/C cofactor …

Sars-Cov-2 Rna-Binding Protein Suppresses Extracellular Mirna Release, Hyejin Mun, Chang Hoon Shin, Qingxuan Fei, Andrea Estefania Lopez Giraldo, Kyoung-Min Choi, Ji Won Lee, Kyungmin Kim, Kyung-Won Min, Leilei Shi, Mark T Bedford, Dong-Chan Kim, Yoo Lim Chun, Seonghyun Ryu, Dongin Kim, Jeong Ho Chang, Ryan T Westrope, Michelle Shay, Edward Nguyen, Junho K Hur, Abigail Agyenda, Nam Chul Kim, Sung-Ung Kang, Woonghee Lee, Je-Hyun Yoon

Faculty, Staff and Student Publications

SARS-CoV-2 is the betacoronavirus causing the COVID-19 pandemic. Although the SARS-CoV-2 genome and transcriptome were reported previously, the function of individual viral proteins is largely unknown. Utilizing biochemical and molecular biology methods, we identified that four SARS-CoV-2 RNA-binding proteins (RBPs) regulate the host RNA metabolism by direct interaction with mature miRNA let-7b revealed by Nuclear Magnetic Resonance spectroscopy (NMR). SARS-CoV-2 RBP Nsp9 primarily binds mature miRNA let-7b, a direct ligand of the Toll-like Receptor 7 (TLR7), one of the potential SARS-CoV-2 therapeutics. Nsp9 suppresses host gene expression possibly by promoting let-7b-mediated silencing of a cellular RNA polymerase, POLR2D. In addition, …

Impact Of Peripheral Circadian Misalignment And Alcohol On The Resiliency Of Intestinal Barrier And Microbiota, Laura Tran, Maliha Shaikh, Phillip A Engen, Ankur Naqib, Dulce M Frausto, Vivian Ramirez, Malia Gasteier, Zlata Bogin, Kristi Lawrence, Lijuan Zhang, Shiwen Song, Stefan J Green, Faraz Bishehsari, Christopher B Forsyth, Ali Keshavarzian, Garth R Swanson

Faculty, Staff and Student Publications

Circadian organization is involved in many gastrointestinal tract (GIT) functions such as the maintenance of intestinal barrier integrity. There is compelling evidence that perturbation of the circadian clock decreases intestinal epithelial cells' resiliency to alcohol-induced injury. One of the most common causes of circadian misalignment is wrong-time eating (largest meal at dinner) in modern societies. Yet, few studies have examined the importance of peripheral circadian rhythms of the GIT to alcohol consumption. Eating patterns during physiologic rest time, defined as wrong-time eating (WTE), misalign the peripheral circadian clock of the GIT and the body's central clock. This study aims to …

A Review Of Engraftment Assessments Following Fecal Microbiota Transplant, Chloe Herman, Bridget M Barker, Thais F Bartelli, Vidhi Chandra, Rosa Krajmalnik-Brown, Mary Jewell, Le Li, Chen Liao, Florencia Mcallister, Khemlal Nirmalkar, Joao B Xavier, J Gregory Caporaso

Faculty, Staff and Student Publications

Fecal Microbiota Transplant (FMT) is a treatment for recurrent Clostridium difficile infections and is being explored for other clinical applications, from alleviating digestive and neurological disorders, to restoring microbiomes impacted by cancer treatment. Quantifying the extent of engraftment following an FMT is important in understanding a recipient's response to treatment. Engraftment and clinical response need to be investigated independently to evaluate an FMT's role (or lack thereof) in achieving a clinical response. Standardized bioinformatics methodologies for quantifying engraftment extent would not only improve assessment and understanding of FMT outcomes, but also facilitate comparison of FMT results and protocols across studies. …

Does Reducing Videofluoroscopy Frame Rate Affect Dige/St Grades In Modified Barium Swallow Studies?, Shitong Mao, Carla L Warneke, Sheila N Buoy, Ariana J Sahli, Brinda Rao Korivi, Carly E A Barbon, Kristy K Brock, Katherine A Hutcheson

Faculty, Staff and Student Publications

Understanding the effects of reduced frame rates on the reliability of Modified Barium Swallow (MBS) ratings for swallowing safety and efficiency is essential for clinical practice. While previous research has examined frame rate (simulated pulse rates) implications concerning penetration, aspiration, and residue ratings, the impact on summary grading systems like the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) remains unclear. This study analyzed a total of 315 full MBS videos collected from 278 patients, and 76.25% of patients were diagnosed with head and neck cancer (mean age 62.51 years, SD 8.53; 12.23% female). We performed pairwise comparisons of DIGEST grades …

Secretory Iga Dysfunction Underlies Poor Prognosis In Fusobacterium-Infected Colorectal Cancer, Ilseok Choi, Kyung-A Kim, Sang Cheol Kim, Donghwan Park, Ki Taek Nam, Jun Hyung Cha, Seungbyn Baek, Junha Cha, Hye-Yeong Jo, Minsun Jung, Melody Y Zeng, Irina Matei, Susan Bullman, Joong Bae Ahn, Yoon Dae Han, Han Sang Kim, Insuk Lee

Faculty, Staff and Student Publications

Fusobacterium nucleatum (Fn) is commonly enriched in colorectal cancer (CRC) and associated with poor outcomes, though its mechanisms remain unclear. Our study investigated how Fn affects the tumor microenvironment through single-cell transcriptomic analyses of 42 CRC patient tissues, comparing Fn-positive and Fn-negative tumors. We discovered that Fn impairs IgA plasma cell development and secretory IgA (sIgA) production by disrupting communication with tumor-associated macrophages. Additional experiments in germ-free mice, together with our re-analysis of a publicly available single-cell RNA-seq data set from a CRC mouse model with an intact gut microbiome–both models having been orally gavaged with Fn–jointly validated the causal …

Tumor Intrinsic Mettl5 Modulates Atf4 Translation To Prevent T Cell-Induced Ferroptosis In Ovarian Cancer, Jiakai Hou, Cheng-Wei Ju, Nicholas A Egan, Yanjun Wei, Yunfei Wang, Minghao Dang, Tianyi Zhou, Leilei Shi, Ningbo Zheng, Si Chen, Ashley M Guerrero, Xiaofang Liang, Wanfu Wu, Areej Akhtar, Chitra Dhiman, Debanwita Roy Burman, Andro E Gerges, Mason D Flores, Han Li, Li-Sheng Zhang, Marleen Kok, Xiaobo Mao, Linghua Wang, Qin Feng, Yiwen Chen, Sanghoon Lee, Daniel J Mcgrail, Nidhi Sahni, Chuan He, Amir A Jazaeri, Weiyi Peng

Faculty, Staff and Student Publications

Poor clinical responses to immune checkpoint blockade (ICB) observed in ovarian cancer (OC) highlight an unmet need to understand the mechanisms driving immune evasion in this disease. To address this, an integrative analysis is conducted by combining in vitro genome‐wide immune screens, in vivo ICB screens, and clinical data mining, and METTL5 is identified as a crucial OC‐intrinsic factor that promotes immune resistance. Immunologically “cold” OC tumors and poor responders to ICB exhibit elevated METTL5 expression. Mechanistically, knocking out (KO) METTL5 in OC disrupts ATF4 translation by altering 18S rRNA m6A levels, leading to the downregulation of SLC7A11 and SLC3A2 …

Perceived Utility Of Genetic Carrier Screening In A Diverse Patient Population, Jack A Colleran, Meagan Choates, Syed Hashmi, Brittanie Shelton, Aranza Gonzalez Cendejas, Angela Haynes Burgess, Blair K Stevens

Faculty, Staff and Student Publications

Current reproductive guidelines call for offering expanded carrier screening (ECS) for genetic conditions. Currently available panels can include screening for carrier status of tens to hundreds of autosomal recessive and/or X-linked conditions. Clinical utility is based on alterations to reproductive decision-making, but study cohorts supporting the utility of ECS largely consist of individuals of European ancestry who are highly educated, of high income, and who often receive preconception counseling. There is a lack of research on the views of patients from diverse backgrounds. Therefore, we aimed to assess and compare perceptions of the utility of ECS and targeted carrier screening …

Kras Inhibition Activates An Actionable Cd24 "Do Not Eat Me" Signal In Pancreatic Cancer, Yongkun Wei, Minghui Liu, Er-Yen Yen, Jun Yao, Zhenzhen Xun, Phuoc T Nguyen, Xiaofei Wang, Zecheng Yang, Abdelrahman Yousef, Dean Pan, Yanqing Jin, Ching-Fei Li, Madelaine S Theardy, Jangho Park, Yiming Cai, Mitsunobu Takeda, Matthew Vasquez, Elizabeth M Park, David H Peng, Yong Zhou, Hong Zhao, Timothy P Heffernan, Andrea Viale, Huamin Wang, Stephanie S Watowich, Han Liang, Dan Zhao, Ronald A Depinho, Wantong Yao, Haoqiang Ying

Faculty, Staff and Student Publications

KRASG12C inhibitors (G12Ci) have produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment is therefore crucial. To better understand the function of KRASG12C and possible G12Ci bypass mechanisms, we developed an autochthonous KRASG12C-driven PDAC model. Compared to the classical KRASG12D PDAC model, the G12C model exhibits slower tumor growth, yet similar histopathological and molecular features. Aligned with clinical experience, G12Ci treatment of KRASG12C tumors produced modest impact despite stimulating a ‘hot’ tumor immune microenvironment. Immunoprofiling revealed that CD24, a ‘don’t eat me’ signal, is significantly upregulated on cancer …

Clinical Outcomes Of Adult Patients With Newly Diagnosed Mixed Phenotype Acute Leukemia, Hannah Goulart, Farhad Ravandi, Nicholas J Short, Nitin Jain, Naval Daver, Tapan M Kadia, Courtney Dinardo, Gautam Borthakur, Koichi Takahashi, Naveen Pemmaraju, Fadi G Haddad, Guillermo Montalban Bravo, Yesid Alvarado, Ghayas C Issa, Alex Bataller, Sherry Pierce, Sanam Loghavi, Guilin Tang, Sa A Wang, Beenu Thakral, Elizabeth Shpall, Richard Champlin, Issa Khouri, Partow Kebriaei, Guillermo Garcia-Manero, Koji Sasaki, Elias J Jabbour, Jayastu Senapati

Faculty, Staff and Student Publications

Purpose: Mixed phenotype acute leukemia (MPAL) is a rare clinical entity with historically poor outcomes.

Methods: We conducted a retrospective analysis of adults 18 years and older with newly diagnosed B-cell (B/M) or T-cell/myeloid (T/M) MPAL treated at our institution between 2017 and 2024.

Results: We identified 42 patients (median age 70 years); 20 (48%) had B/M MPAL, and 22 (52%) had T/M MPAL; 57% of patients had adverse risk cytogenetics, and 41% had a TP53 mutation. Sixty-two percent of patients were treated with a hybrid regimen, and 45% of patients received intensive therapy. A composite complete remission (CRc; CR …

Fusobacterium Sphaericum Sp Nov, Isolated From A Human Colon Tumor Adheres To Colonic Epithelial Cells And Induces Il-8 Secretion, Martha A Zepeda-Rivera, Yannick Eisele, Alexander Baryiames, Hanrui Wu, Claudia Mengoni, Gianmarco Piccinno, Elsa F Mcmahon, Kaitlyn D Lacourse, Dakota S Jones, Hans Hauner, Samuel S Minot, Nicola Segata, Floyd E Dewhirst, Christopher D Johnston, Susan Bullman

Faculty, Staff and Student Publications

Cancerous tissue is a largely unexplored microbial niche that provides a unique environment for the colonization and growth of specific bacterial communities, and with it, the opportunity to identify novel bacterial species. Here, we report distinct features of a novel Fusobacterium species, F. sphaericum sp. nov. (Fs), isolated from primary colon adenocarcinoma tissue. We acquire the complete closed genome and associated methylome of this organism and phylogenetically confirm its classification into the Fusobacterium genus, with F. perfoetens as its closest neighbor. Fs is phenotypically and genetically distinct, with morphological analysis revealing its coccoid shape, that while similar to …

Addressing Controversy In Fusobacterium Nomenclature: What Exactly Does “F Nucleatum” Refer To?, Martha A Zepeda-Rivera, Floyd E Dewhirst, Susan Bullman, Christopher D Johnston

Faculty, Staff and Student Publications

The F. nucleatum group (sensu lato) is historically composed of four subspecies (F. nucleatum subsp. animalis, F. nucleatum subsp. nucleatum, F. nucleatum subsp. polymorphum, F. nucleatum subsp. vincentii). Although F. nucleatum sensu lato members are typically associated with oral disease, they have recently been shown to disseminate to the gastrointestinal tract and are associated with adverse health conditions such as inflammatory bowel disease and colorectal cancer (CRC). A growing debate over the nomenclature applied to Fusobacterium taxonomy has resulted in different names for these lineages, shifting them from their historic subspecies designations to …

Knowledge Mapping And Visualized Analysis Of Research Progress In Onconephrology: A Bibliometric Analysis, Yiwei Wang, Shuling Fan, Wei Wang

Faculty, Staff and Student Publications

Objectives: Onconephrology is an expanding subspecialty focused on the management of cancer patients with renal injury. This study used a comprehensive bibliometric analysis to emphasize the need for cooperation between oncologists and nephrologists, exploring current trends and future research areas in onconephrology.

Methods: Relevant literature on onconephrology published between 1 January 2000 and 27 April 2024 was retrieved from the Science Citation Index Expanded of the Web of Science Core Collection, followed by manual screening. Bibliometric analyses were performed using CiteSpace, VOSviewer, and Bibliometrix software.

Results: A total of 1,853 publications, including 1,647 articles and 206 reviews, by 11,606 authors …

Lymphodepletion, Tumor-Infiltrating Lymphocytes, And High Versus Low Dose Il-2 Followed By Pembrolizumab In Patients With Metastatic Melanoma, Merve Hasanov, Simin Kiany, Marie-Andrée Forget, Roland Bassett, Michael A Davies, Adi Diab, Jeffrey E Gershenwald, Isabella C Glitza, Jeffrey E Lee, Anthony Lucci, Jennifer L Mcquade, Sapna P Patel, Merrick I Ross, Hussein A Tawbi, Jennifer A Wargo, Michael K Wong, Chantale Bernatchez, Patrick Hwu, Cara Haymaker, Rodabe N Amaria

Faculty, Staff and Student Publications

This study evaluated the efficacy and safety of unengineered tumor-infiltrating lymphocytes (TILs) combined with pembrolizumab and either high (HD, Arm-1) or low (LD, Arm-2) doses of IL-2 in patients with metastatic melanoma (MM). Patients were lymphodepleted with cyclophosphamide and fludarabine, followed by TIL infusion and IL-2 (Arm-1: 720,000 IU/kg IV q 8 hrs up to 15 doses; Arm-2: 2 million IU SC for 14 days). Patients received pembrolizumab 200 mg IV starting 21 days post-TIL infusion, and every 3 weeks for up to 2 years. The primary endpoint was overall response rate (ORR) per RECIST 1.1. Blood samples were collected …

The Kiva System Versus Balloon Kyphoplasty For Vertebral Compression Fracture: A Meta-Analysis Of Randomized Control Trials, Humaid Al Farii, Nikhil Gattu, Caleb M Yeung, Christopher A Alvarez-Breckenridge, Robert Y North, Claudio E Tatsui, Laurence D Rhines, Valerae O Lewis, Justin E Bird, Shalin S Patel

Faculty, Staff and Student Publications

Background: Vertebral compression fractures (VCFs) are the most common type of vertebral body fracture. The Kiva VCF Treatment System is a relatively novel technique to manage VCFs. The aim of this study was to compare the efficacy of Kiva versus standard Balloon Kyphoplasty (BK) through evaluation of published randomized controlled trials (RCTs).

Methods: This study was performed following the guidelines for PRISMA. We performed a systematic literature search using PubMed and MEDLINE in June 2023. The search keywords were "Kiva" and "Kyphoplasty" which yielded a total of 112 articles. Outcome measures included pain, measured through the Visual Analogue Scale (VAS) …

The Role Of Neutrophils In Vasospasm And Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: Is It Time For A Sah Clinical Trial Targeting Neutrophils?, William W Wroe, Hussein A Zeineddine, Spiros L Blackburn, Jaroslaw Aronowski, Devin W Mcbride

Faculty, Staff and Student Publications

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological disease, and one of the primary drivers of morbidity after aneurysm rupture is the phenomenon of delayed cerebral ischemia (DCI). Significant knowledge has been gained over the past two decades of the impact of neuroinflammation in DCI; and neutrophils are now believed to play a major role. There is significant human subject data showing the rise of neutrophil related inflammatory markers and neutrophil's association with poor outcome after aSAH, but as of yet no trials involving human subjects have been done specifically targeting neutrophils. There is however a growing body of evidence …

Statistical Innovations In Clinical Trial Design With A Focus On Drug Combinations, Factorials, And Other Multiple Therapy Issues, Donald A Berry

Faculty, Staff and Student Publications

Statistical methods in clinical research tend to become entrenched. Innovations threaten the status quo. The "right way" becomes frozen in lore. This is so even when the "right way" is not best. "Statistical significance" and the associated requirement of "high power" is an example. This attitude is an impediment to efficient design. Willingness to address some design issues with moderate power enables building highly informative and highly efficient clinical trials. This article considers several types of clinical trials, including dose-finding, combinations, and factorial designs. Bayesian adaptive methods are used to show that trials can be made more efficient and more …

Differential Microrna Profiling Of Blood L1cam And Bulk Extracellular Vesicles In Bipolar Disorder, Gabriel R Fries, Salahudeen Mirza, Jun Wang, Camila N C Lima, Wei Zhang, Marcela Carbajal Tamez, Giselli Scaini, Jair C Soares, Joao Quevedo

Faculty, Staff and Student Publications

Objective: This preliminary study aimed to identify microRNA (miRNA) signatures associated with bipolar disorder (BD) by profiling blood-derived extracellular vesicles (EVs) of both putative neuronal origin and from all sources.

Method: In two parallel studies of individuals with BD and controls (CON), we characterized miRNA expression profiles of blood EVs selected for L1CAM, a putative marker of neuronal origin (n = 20 BD/20 CON), as well as bulk EVs (n = 21 BD/20 CON). For each study, analyses identified miRNAs differentially expressed between groups, followed by functional interrogation and testing for associations with clinical features.

Results: Results of …

Cutting Edge Developments In Bone Oncology – Highlights From The Cancer And Bone Society 2024 Annual Meeting, Deanna N Edwards, Shreya Patel, Gabriel M Pagnotti

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The 2024 Annual Conference of the Cancer and Bone Society (CABS), held jointly with the Bone Research Society at the University of Sheffield, highlighted the Society's enduring mission to advance understanding of cancer-bone interactions through collaboration, mentorship, and scientific excellence. Established from the early Cancer Induced Bone Disease meetings and re-emerging as an independent body in 2016, CABS continues to serve as a global community bridging basic, translational, and clinical research. This year's meeting featured a comprehensive scientific program spanning tumor-bone biology, therapeutic innovation, and microenvironmental regulation. Clinical sessions emphasized the evolution of bone-targeted treatments such as bisphosphonates, denosumab, and …

Stage- And Smoking-Associated Microrna Expression In Lung Adenocarcinoma, Min Huang, Yimin Ge, Huiqin Chen, Caimiao Wei, David Cogdell, Cristina Ivan, Meng Chen, Wei Zhang, George A Calin, Ming Guo

Faculty, Staff and Student Publications

Background: Altered expression of microRNAs (miRNAs) is implicated in lung carcinogenesis, but little research has investigated the association of miRNA alterations with lung cancer stage or smoking status. To identify such alterations in lung adenocarcinoma, we conducted miRNA profiling.

Methods: Lung adenocarcinoma specimens and paired nonneoplastic lung tissues from 58 patients who had received no preoperative therapy and underwent tumor resection from 1991 to 2006 were collected from tumor tissue banks. Thirty (52%) of the tumors were stage I and 28 (48%) stage II or higher. Twenty-five (43%) patients were nonsmokers and 33 (57%) were smokers. To identify miRNAs of …

Benchmarking Dna Foundation Models For Genomic And Genetic Tasks, Haonan Feng, Lang Wu, Bingxin Zhao, Chad Huff, Jianjun Zhang, Jia Wu, Lifeng Lin, Peng Wei, Chong Wu

Faculty, Staff and Student Publications

The rapid evolution of DNA foundation models promises to revolutionize genomics, yet comprehensive evaluations are lacking. Here, we present a comprehensive, unbiased benchmark of five models (DNABERT-2, Nucleotide Transformer V2, HyenaDNA, Caduceus-Ph, and GROVER) across diverse genomic and genetic tasks including sequence classification, gene expression prediction, variant effect quantification, and topologically associating domain (TAD) region recognition, using zero-shot embeddings. Our analysis reveals that mean token embedding consistently and significantly improves sequence classification performance, outperforming other pooling strategies. Model performance varies among tasks and datasets; while general purpose DNA foundation models showed competitive performance in pathogenic variant identification, they were less …