Digital Commons Network^™

The 10 Commandments Of Endo-Bentall Repair, Mehrdad Ghoreishi

All Publications

No abstract available

Exploit The Potential Clinical Benefit Of Using Proton Arc Therapy For Esophageal Cancer, Peilin Liu, Xiaoda Cong, Raymond Dalfsen, Martin Soukup, James E. Dolan, Shupeng Chen, Craig Stevens, Rohan Deroniyagala, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

No abstract provided.

Quantitative Evaluation Of Gantry Rotation Perturbation Effects On Spot-Scanning Arc Therapy (Sparc), Peilin Liu, Lewei Zhao, Gang Liu, Xiaoda Cong, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To quantitatively assess the impact of random gantry rotation perturbations on spot-scanning arc (SPArc) therapy.

Methods:

To simulate random gantry rotation perturbations, the initial gantry angle of SPArc treatment plans was modified using an in-house script. Four cases from different disease sites include brain, lung, liver and prostate were selected to evaluate. Original SPArc plans (SPArc_org) were developed through iterative processes, including control point re-sampling, redistribution of control points & energy layers, energy layer filtration, and re-sampling. Considering potential limitations, rotation perturbations of 1mm and 2mm were applied to al SPArc_org plans to generate perturbed SPArc …

A Multifactorial Study Of Factors Influencing Self-Health Behaviors In Dementia, Elizabeth Malkin

Dissertations

The global increase in dementia cases presents a significant public health challenge, particularly given the absence of a cure and the rising healthcare burden on individuals and society. This study aims to examine the influence of knowledge, beliefs, and motivation on self-health behaviors to mitigate the risk of dementia among individuals residing in the United States. With the use of an online survey, the study utilized the U.S. normed MCLHB-DRR scale and supplemental questions about knowledge of risk factors and degree of closeness to family members with dementia to determine whether (1) more closely related relatives (first-degree relatives) and those …

Infertility’S Impact On Couples’ Functioning, Elizabeth Sanders

Dissertations

Historically, infertility has been a taboo topic of discussion and is often avoided in conversation because of the stigmatization of the diagnosis. According to the World Health Organization (2022), infertility affects 186 million individuals globally. However, there seems to be a gap in the research as it pertains to the psychological well-being and treatment of men and women diagnosed with this condition. While it has become less of a feared topic, it still is not discussed or researched enough, thus further exacerbating the gap in research on mental health and treatment options. The following dissertation completed a critical review of …

Transformational Leadership Teams And Implementing Multi-Tiered Systems Of Support [Mtss] In The Context Of An Urban All-Male Catholic High School: Bridging The Gap To Academic Identity And Student Efficacy, Markeise R. Russell

Dissertations

This study explored the implementation of Multi-Tiered Systems of Support (MTSS) at Garfield High School, an urban all-male Catholic high school in Chicago. The study aimed to understand the perceptions and experiences of school leaders and stakeholders in facilitating MTSS implementation. Using Tony Wagner's 4C Framework of Context, Culture, Conditions, and Competencies, the researcher assessed the current state ("As-Is") of the MTSS and envisioned the desired future state ("To-Be"). A qualitative research design was employed, involving interviews, focus groups, and document analysis to gather in-depth insights from administrators, teachers, and support staff. The purpose of the study was to identify …

Evaluation Of Educator Outcomes Of Teaching Social-Emotional Learning, Mindfulness, And Life Skills, Gary Mccarthy

Dissertations

There have been many studies documenting the benefits of social – emotional (SEL) instruction for students, but fewer on how teaching SEL curriculums may alleviate teacher burnout. I used a mixed methods research design to investigate the impact of teaching social-emotional learning, mindfulness, and life skills through The Leader in Me (LiM), a K-12 whole-school improvement model based on The 7 Habits of Highly Effective People on educators. The outcomes of surveys and interviews indicated that most educators in my study reported personal and professional benefits from teaching and modeling the program. My recommendations include further implementation of SEL, Mindfulness, …

Tev Analysis Of A Source-Rich Region With The Hawc Observatory: Is Hess J1809-193 A Potential Hadronic Pevatron?, A. Albert, R. Alfaro, C. Alvarez, J. C. Arteaga-Velázquez, D. Avila Rojas, R. Babu, E. Belmont-Moreno, A. Bernal, M. Breuhaus, K. S. Caballero-Mora, T. Capistrán, A. Carramiñana, S. Casanova, J. Cotzomi, E. De La Fuente, D. Depaoli, N. Di Lalla, R. Diaz Hernandez, B. L. Dingus, M. A. Duvernois, C. Espinova, K. L. Fan, K. Fang, B. Fick, N. Fraija, J. A. Garcia-Gonzalez, F. Garfias, A. Gonzalez Munoz, M. M. Gonzalez, J. A. Goodman, S. Groetsch, J. P. Harding, S. Hernandez-Cadena, I. Herzog, D. Huang, F. Hueyotl-Zahuantitla, P. Huntemeyer, A. Iriarte, V. Joshi, S. Kaufmann, A. Lara, J. Lee, H. Leon Vargas, A. L. Longinotti, G. Luis-Raya, K. Malone, J. Martines-Castro, J. A. Matthews, P. Miranda-Romagnoli, J. A. Montes, J. A. Morales-Soto, E. Moreno, M. Mostafa, L. Nellen, M. Newbold, M. U. Nisa, R. Noriega-Papaqui, M. Osorio, Y. Perez Araujo, E. G. Perez-Perez, C. D. Rho, D. Rosa-Gonzalez, E. Ruiz-Velasco, H. Salazar, A. Sandoval, M. Schneider, J. Serna-Franco, A. J. Smith, Y. Son, R. W. Springer, O. Tibolla, K. Tollefson, I. Torres, R. Torres-Escobedo, R. Turner, F. Urena-Mena, E. Varela, Xiaojie Wang, I. J. Watson, E. Willox, S. Yun-Carcamo, H. Zhou

Physics Faculty Research & Creative Works

HESS J1809-193 is an unidentified TeV source, first detected by the High Energy Stereoscopic System (H.E.S.S.) collaboration. The emission originates in a source-rich region that includes several supernova remnants (SNRs) and pulsars including SNR G11.1+0.1, SNR G11.0-0.0, and the young radio pulsar PSR J1809-1917. Originally classified as a pulsar wind nebula candidate, recent studies show the peak of the TeV region overlapping with a system of molecular clouds. This resulted in the revision of the original leptonic scenario to look for alternate hadronic scenarios. Marked as a potential PeVatron candidate, this region has been studied extensively by H.E.S.S. due to …

Performance Of The Hawc Observatory And Tev Gamma-Ray Measurements Of The Crab Nebula With Improved Extensive Air Shower Reconstruction Algorithms, A. Albert, R. Alfaro, C. Alvarez, A. Andrés, J. C. Arteaga-Velázquez, D. Avila Rojas, H. A. Ayala Solares, R. Babu, E. Belmont-Moreno, A. Bernal, K. S. Caballero-Mora, T. Capistrán, A. Carramiñana, F. Carreón, S. Casanova, U. Cotti, J. Cotzomi, S. Coutiño De León, E. De La Fuente, C. De Leon, D. Depaoli, N. Di Lalla, R. Diaz Hernandez, B. L. Dingus, M. A. Duvernois, K. Engel, T. Ergin, C. Espinoza, K. L. Fan, K. Fang, N. Fraija, S. Fraija, J. A. Garcia-Gonzalez, F. Garfias, H. Goksu, M. M. Gonzalez, J. A. Goodman, S. Groetsch, J. P. Harding, S. Hernandez-Cadena, I. Herzog, J. Hinton, D. Huang, F. Hueyotl-Zahuantitla, P. Huntemeyer, A. Iriarte, S. Kaufmann, A. Lara, J. Lee, H. Leon Vargas, J. T. Linnemann, A. L. Longinotti, G. Luis-Raya, K. Malone, J. Martinez-Castro, J. A. Matthews, P. Miranda-Romagnoli, J. A. Montes, E. Moreno, M. Mostafa, L. Nellen, M. U. Nisa, R. Noriega-Papaqui, L. Olivera-Nieto, N. Omodei, M. Osorio-Archila, Y. Perez Araujo, E. G. Perez-Perez, C. D. Rho, D. Rosa-Gonzalez, E. Ruiz-Velasco, H. Salazar, D. Salazar-Gallegos, A. Sandoval, M. Schneider, G. Schwefer, J. Serna-Franco, A. J. Smith, Y. Son, R. W. Springer, O. Tibolla, K. Tollefson, I. Torres, R. Torres-Escobedo, R. Turner, F. Urena-Mena, E. Varela, Xiaojie Wang, I. J. Watson, K. Whitaker, E. Willox, H. Wu, S. Yu, S. Yun-Carcamo, H. Zhou

Physics Faculty Research & Creative Works

The High-Altitude Water Cherenkov (HAWC) Gamma-Ray Observatory, located on the side of the Sierra Negra volcano in Mexico, has been fully operational since 2015. The HAWC collaboration has recently significantly improved their extensive air shower reconstruction algorithms, which has notably advanced the observatory performance. The energy resolution for primary gamma rays with energies below 1 TeV was improved by including a noise-suppression algorithm. Corrections have also been made to systematic errors in direction fitting related to the detector and shower plane inclinations, O ( 0 .° 1 ) biases in highly inclined showers, and enhancements to the core reconstruction. The …

Observation Of The Galactic Center Pevatron Beyond 100 Tev With Hawc, A. Albert, R. Alfaro, C. Alvarez, A. Andrés, J. C. Arteaga-Velázquez, D. Avila Rojas, H. A. Ayala Solares, R. Babu, E. Belmont-Moreno, A. Bernal, K. S. Caballero-Mora, T. Capistrán, A. Carramiñana, S. Casanova, U. Cotti, J. Cotzomi, S. Coutiño De León, E. De La Fuente, C. De Leon, D. Depaoli, N. Di Lalla, R. Diaz Hernandez, B. L. Dingus, M. A. Duvernois, J. C. Diaz-Velez, K. Engel, T. Ergin, C. Espinoza, K. L. Fan, K. Fang, N. Fraija, S. Fraija, J. A. Garcia-Gonzalez, F. Garfias, H. Goksu, M. M. Gonzalez, J. A. Goodman, S. Groetsch, J. P. Harding, S. Hernandez-Cadena, I. Herzog, J. Hinton, D. Huang, F. Hueyotl-Zahuantitla, T. B. Humensky, P. Huntemeyer, A. Iriarte, S. Kaufmann, D. Kieda, A. Lara, W. H. Lee, J. Lee, H. Leon Vargas, J. T. Linnemann, A. L. Longinotti, G. Luis-Raya, K. Malone, O. Martinez, J. Martinez-Castro, J. A. Matthews, P. Miranda-Romagnoli, J. A. Montes, J. A. Morales-Soto, E. Moreno, M. Mostafa, M. Najafi, L. Nellen, M. Newbold, M. U. Nisa, R. Noriega-Papaqui, L. Olivera-Nieto, N. Omodei, M. Osorio-Archila, Y. Perez Araujo, E. G. Perez-Perez, C. D. Rho, D. Rosa-Gonzalez, E. Ruiz-Velasco, H. Salazar, D. Salazar-Gallegos, A. Sandoval, M. Schneider, G. Schwefer, J. Serna-Franco, A. J. Smith, Y. Son, R. W. Springer, O. Tibolla, K. Tollefson, I. Torres, R. Torres-Escobedo, R. Turner, F. Urena-Mena, E. Valera, Xiaojie Wang, Z. Wang, I. J. Watson, E. Willox, H. Wu, S. Yu, S. Yun-Carcamo, H. Zhou

Physics Faculty Research & Creative Works

We report an observation of ultrahigh-energy (UHE) gamma rays from the Galactic center (GC) region, using 7 yr of data collected by the High-Altitude Water Cherenkov (HAWC) Observatory. The HAWC data are best described as a point-like source (HAWC J1746-2856) with a power-law spectrum ( d N / d E = ϕ E / 26 TeV γ ), where γ = −2.88 ± 0.15stat − 0.1sys and ϕ = 1.5 x 10⁻¹⁵ (TeV cm² s)⁻¹ ± 0.3 stat − 0.13 sys + 0.08 sys extending from 6 to 114 TeV. We find no evidence of a spectral …

Cover Crop And Wheel-Track Effects On Soil Properties Under Cotton Production In Eastern Arkansas, Shelby G. Lebeau, Kristofor R. Brye, Michael Daniels, Lisa S. Wood

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Repetitive use of heavy farm machinery in cultivated agriculture may cause soil compaction that can adversely affect soil-health-related properties. Cover crops (CC) are well-documented to alleviate problems associated with compaction and improve overall soil health in time. The objective of this field study was to evaluate the cumulative effects of CC treatment (i.e., with ≥ 6 years cereal rye [Secale cereale L.] CC and ≥ 4 years with no cover crop [NCC]) and sample/measurement placement (i.e., in the bed [B] and in the wheel-track [WT] and no-wheel-track [NWT] furrow) on near-surface soil physical-, chemical-, and infiltration-related properties in an …

Early Season Wheat Response To Electrochemically Precipitated Struvite In Various Soils In The Greenhouse, Tatum Simms, Kristofor R. Brye, Trenton L. Roberts, Lauren F. Greenlee

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Fertilizer-phosphorus (P) materials can be recovered from wastewater and used to supplement mined phosphate rock, where one such material is struvite [MgNH4PO4·6(H2O)]. This study aimed to compare electrochemically precipitated struvite (ECST) reclaimed from synthetic wastewater to other commercial fertilizer-P sources in cultivated soils from Arkansas [silty clay loam (AR-SiCL) and silt loam (AR-SiL)], Missouri [(silt loam; MO-SiL 1 and 2)], and Nebraska [silt loam (NE-SiL) and sandy loam (NE-SL)]. A greenhouse pot study was conducted for 60 days with unvernalized wheat (Triticum aestivum) using five fertilizer-P sources [ECST, chemically precipitated struvite (CPST), monoammonium phosphate (MAP), triple superphosphate (TSP), …

Against: Adoption Of New Technologies In Radiation Oncology Must Be Evidence-Based, Xuanfeng Ding

Conference Presentation Abstracts

No abstract provided.

Behind Armor Blunt Trauma: Liver Injuries Using A Live Animal Model, Narayan Yoganandan, Alok Shah, Brian D. Stemper, Lewis Somber, Valeta Carol Chancey, Joseph Mcentire

Biomedical Engineering Faculty Research and Publications

Introduction

While the 44-mm clay penetration criterion was developed in the 1970s for soft body armor applications, and the researchers acknowledged the need to conduct additional tests, the same behind the armor blunt trauma displacement limit is used for both soft and hard body armor evaluations and design considerations. Because the human thoraco-abdominal contents are heterogeneous, have different skeletal coverage, and have different functional requirements, the same level of penetration limit does not imply the same level of protection. It is important to determine the regional responses of different thoraco-abdominal organs to better describe human tolerance and improve the current …

The Shriners Children's Standard Gait Model (Scgm), Karen M. Kruger, Patrick Fischer, Sam Augsburger, Jing Feng, Jean-Francois Girouard, Daniel L. Gregory, Logan Johnson, Bruce A. Macwilliams, Mark L. Mcmulkin, Bradley Nelson, Spencer Warshauer, Prabhav Saraswat, Ross S. Chafetz

Biomedical Engineering Faculty Research and Publications

No abstract provided.

Ataxia Telangiectasia And Rad3-Related (Atr) Inhibitor Camonsertib Dose Optimization In Patients With Biomarker-Selected Advanced Solid Tumors (Tresr Study), Elisa Fontana, Ezra Rosen, Elizabeth K Lee, Martin Højgaard, Niharika B Mettu, Stephanie Lheureux, Benedito A Carneiro, Gregory M Cote, Louise Carter, Ruth Plummer, Devalingam Mahalingam, Adrian J Fretland, Joseph D Schonhoft, Ian M Silverman, Marisa Wainszelbaum, Yi Xu, Danielle Ulanet, Maria Koehler, Timothy A Yap

Faculty, Staff and Student Publications

BACKGROUND: Camonsertib is a selective oral inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase with demonstrated efficacy in tumors with DNA damage response gene deficiencies. On-target anemia is the main drug-related toxicity typically manifesting after the period of dose-limiting toxicity evaluation. Thus, dose and schedule optimization requires extended follow-up to assess prolonged treatment effects.

METHODS: Long-term safety, tolerability, and antitumor efficacy of 3 camonsertib monotherapy dosing regimens were assessed in the TRESR study dose-optimization phase: 160 mg once daily (QD) 3 days on, 4 days off (160 3/4; the preliminary recommended Phase II dose [RP2D]) and two step-down groups of …

Identification Of Hypoxia-Alcamhigh Macrophage- Exhausted T Cell Axis In Tumor Microenvironment Remodeling For Immunotherapy Resistance, Zhenzhen Xun, Huanran Zhou, Mingyi Shen, Yao Liu, Chengcao Sun, Yanhua Du, Zhou Jiang, Liuqing Yang, Qing Zhang, Chunru Lin, Qingsong Hu, Youqiong Ye, Leng Han

Faculty, Staff and Student Publications

Although hypoxia is known to be associated with immune resistance, the adaptability to hypoxia by different cell populations in the tumor microenvironment and the underlying mechanisms remain elusive. This knowledge gap has hindered the development of therapeutic strategies to overcome tumor immune resistance induced by hypoxia. Here, bulk, single-cell, and spatial transcriptomics are integrated to characterize hypoxia associated with immune escape during carcinogenesis and reveal a hypoxia-based intercellular communication hub consisting of malignant cells, ALCAM

Ensemble Pretrained Language Models To Extract Biomedical Knowledge From Literature, Zhao Li, Qiang Wei, Liang-Chin Huang, Jianfu Li, Yan Hu, Yao-Shun Chuang, Jianping He, Avisha Das, Vipina Kuttichi Keloth, Yuntao Yang, Chiamaka S Diala, Kirk E Roberts, Cui Tao, Xiaoqian Jiang, W Jim Zheng, Hua Xu

Faculty, Staff and Student Publications

OBJECTIVES: The rapid expansion of biomedical literature necessitates automated techniques to discern relationships between biomedical concepts from extensive free text. Such techniques facilitate the development of detailed knowledge bases and highlight research deficiencies. The LitCoin Natural Language Processing (NLP) challenge, organized by the National Center for Advancing Translational Science, aims to evaluate such potential and provides a manually annotated corpus for methodology development and benchmarking.

MATERIALS AND METHODS: For the named entity recognition (NER) task, we utilized ensemble learning to merge predictions from three domain-specific models, namely BioBERT, PubMedBERT, and BioM-ELECTRA, devised a rule-driven detection method for cell line and …

Improving Large Language Models For Clinical Named Entity Recognition Via Prompt Engineering, Yan Hu, Qingyu Chen, Jingcheng Du, Xueqing Peng, Vipina Kuttichi Keloth, Xu Zuo, Yujia Zhou, Zehan Li, Xiaoqian Jiang, Zhiyong Lu, Kirk Roberts, Hua Xu

Faculty, Staff and Student Publications

IMPORTANCE: The study highlights the potential of large language models, specifically GPT-3.5 and GPT-4, in processing complex clinical data and extracting meaningful information with minimal training data. By developing and refining prompt-based strategies, we can significantly enhance the models' performance, making them viable tools for clinical NER tasks and possibly reducing the reliance on extensive annotated datasets.

OBJECTIVES: This study quantifies the capabilities of GPT-3.5 and GPT-4 for clinical named entity recognition (NER) tasks and proposes task-specific prompts to improve their performance.

MATERIALS AND METHODS: We evaluated these models on 2 clinical NER tasks: (1) to extract medical problems, treatments, …

Target Engagement And Immunogenicity Of An Active Immunotherapeutic Targeting Pathological Α-Synuclein: A Phase 1 Placebo-Controlled Trial, Pepijn Eijsvogel, Pinaki Misra, Luis Concha-Marambio, Justin D Boyd, Shuang Ding, Lauren Fedor, Yueh-Ting Hsieh, Yu Shuang Sun, Madeline M Vroom, Carly M Farris, Yihua Ma, Marieke L De Kam, Igor Radanovic, Maurits F J M Vissers, Dario Mirski, Ghazal Shareghi, Mohammad Shahnawaz, Wolfgang Singer, Philip Kremer, Geert Jan Groeneveld, Hui Jing Yu, Jean-Cosme Dodart

Faculty, Staff and Student Publications

Investigational therapeutics that target toxic species of α-synuclein (αSyn) aim to slow down or halt disease progression in patients with Parkinson's disease (PD). Here this 44-week, randomized, placebo-controlled, double-blind, single-center phase 1 study investigated safety, tolerability and immunogenicity of UB-312, an active immunotherapeutic targeting pathological αSyn, in patients with PD. The primary outcome measures were adverse event frequency and change in anti-αSyn antibody titers in blood and cerebrospinal fluid (CSF). Exploratory outcomes were changes in clinical scales and biomarker-based target engagement as measured by seed amplification assays. Twenty patients were randomized 7:3 (UB-312:placebo) into 300/100/100 μg or 300/300/300 μg (weeks …

Mechanistic Insights Into Metabolic Function Of Dynamin-Related Protein 1, Xin Li, Katherine Pham, Jazmin Ysaguirre, Iqbal Mahmud, Lin Tan, Bo Wei, Long J Shao, Maryam Elizondo, Rabie Habib, Fathima Elizondo, Hiromi Sesaki, Philip L Lorenzi, Kai Sun

Faculty, Staff and Student Publications

Dynamin-related protein 1 (DRP1) plays crucial roles in mitochondrial and peroxisome fission. However, the mechanisms underlying the functional regulation of DRP1 in adipose tissue during obesity remain unclear. To elucidate the metabolic and pathological significance of diminished DRP1 in obese adipose tissue, we utilized adipose tissue-specific DRP1 KO mice challenged with a high-fat diet. We observed significant metabolic dysregulations in the KO mice. Mechanistically, DRP1 exerts multifaceted functions in mitochondrial dynamics and endoplasmic reticulum (ER)-lipid droplet crosstalk in normal mice. Loss of function of DRP1 resulted in abnormally giant mitochondrial shapes, distorted mitochondrial membrane structure, and disrupted cristae architecture. Meanwhile, …

An Analysis Of Suspected Microplastics In The Muscle And Gastrointestinal Tissues Of Fish From Sarasota Bay, Fl: Exposure And Implications For Apex Predators And Seafood Consumers, Eric Conger, Miranda Dziobak, Elizabeth J Berens Mccabe, Tita Curtin, Ayushi Gaur, Randall S Wells, John E Weinstein, Leslie B Hart

Faculty, Staff and Student Publications

Microplastics have been found in the gastrointestinal (GI) fluid of bottlenose dolphins (Tursiops truncatus), inhabiting Sarasota Bay, FL, suggesting exposure by ingestion, possibly via contaminated fish. To better understand the potential for trophic transfer, muscle and GI tissues from 11 species of dolphin prey fish collected from Sarasota Bay were screened for microplastics (particles <5 mm diameter). Suspected microplastics were found in 82% of muscle samples (n=89), and 97% of GI samples (n=86). Particle abundance and shapes varied by species (p<0.05) and foraging habit (omnivore vs. carnivore, p<0.05). Pinfish (Lagodon rhomboides) had the highest particle abundance for both tissue types (muscle: 0.38 …

Automatic Vessel Attenuation Measurement For Quality Control Of Contrast-Enhanced Ct: Validation On The Portal Vein, Kevin Mccoy, Sujay Marisetty, Dominique Tan, Corey T Jensen, Jeffrey H Siewerdsen, Christine B Peterson, Moiz Ahmad

Faculty, Staff and Student Publications

Background: Adequate image enhancement of organs and blood vessels of interest is an important aspect of image quality in contrast-enhanced computed tomography (CT). There is a need for an objective method for evaluation of vessel contrast that can be automatically and systematically applied to large sets of CT exams.

Purpose: The purpose of this work was to develop a method to automatically segment and measure attenuation Hounsfield Unit (HU) in the portal vein (PV) in contrast-enhanced abdomen CT examinations.

Methods: Input CT images were processed by a vessel enhancing filter to determine candidate PV segmentations. Multiple machine learning (ML) classifiers …

Chemical Screening By Time-Resolved X-Ray Scattering To Discover Allosteric Probes, Chris A Brosey, Todd M Link, Runze Shen, Davide Moiani, Kathryn Burnett, Greg L Hura, Darin E Jones, John A Tainer

Faculty, Staff and Student Publications

Drug discovery relies on efficient identification of small-molecule leads and their interactions with macromolecular targets. However, understanding how chemotypes impact mechanistically important conformational states often remains secondary among high-throughput discovery methods. Here, we present a conformational discovery pipeline integrating time-resolved, high-throughput small-angle X-ray scattering (TR-HT-SAXS) and classic fragment screening applied to allosteric states of the mitochondrial import oxidoreductase apoptosis-inducing factor (AIF). By monitoring oxidized and X-ray-reduced AIF states, TR-HT-SAXS leverages structure and kinetics to generate a multidimensional screening dataset that identifies fragment chemotypes allosterically stimulating AIF dimerization. Fragment-induced dimerization rates, quantified with time-resolved SAXS similarity analysis (k

Dopaminergic Neurons In Zona Incerta Drives Appetitive Self-Grooming, Zhiying Jiang, Michelle He, Claire Young, Jing Cai, Yuanzhong Xu, Yanyan Jiang, Hongli Li, Maojie Yang, Qingchun Tong

Faculty, Staff and Student Publications

Dopaminergic (DA) neurons are known to play a key role in controlling behaviors. While DA neurons in other brain regions are extensively characterized, those in zona incerta (ZITH or A13) receive much less attention and their function remains to be defined. Here it is shown that optogenetic stimulation of these neurons elicited intensive self‐grooming behaviors and promoted place preference, which can be enhanced by training but cannot be converted into contextual memory. Interestingly, the same stimulation increased DA release to periaqueductal grey (PAG) neurons and local PAG antagonism of DA action reduced the elicited self‐grooming. In addition, A13 neurons increased …

Artificial Intelligence-Based Segmentation Of Residual Pancreatic Cancer In Resection Specimens Following Neoadjuvant Treatment (Isgpp-2): International Improvement And Validation Study, Boris V Janssen, Bart Oteman, Mahsoem Ali, Pieter A Valkema, Volkan Adsay, Olca Basturk, Deyali Chatterjee, Angela Chou, Stijn Crobach, Michael Doukas, Paul Drillenburg, Irene Esposito, Anthony J Gill, Seung-Mo Hong, Casper Jansen, Mike Kliffen, Anubhav Mittal, Jas Samra, Marie-Louise F Van Velthuysen, Aslihan Yavas, Geert Kazemier, Joanne Verheij, Ewout Steyerberg, Marc G Besselink, Huamin Wang, Caroline Verbeke, Arantza Fariña, Onno J De Boer, Pancreatobiliary And Hepatic Artificial Intelligence Research (Phair) Consortium, International Study Group Of Pancreatic Pathologists (Isgpp);

Faculty, Staff and Student Publications

Neoadjuvant therapy (NAT) has become routine in patients with borderline resectable pancreatic cancer. Pathologists examine pancreatic cancer resection specimens to evaluate the effect of NAT. However, an automated scoring system to objectively quantify residual pancreatic cancer (RPC) is currently lacking. Herein, we developed and validated the first automated segmentation model using artificial intelligence techniques to objectively quantify RPC. Digitized histopathological tissue slides were included from resected pancreatic cancer specimens from 14 centers in 7 countries in Europe, North America, Australia, and Asia. Four different scanner types were used: Philips (56%), Hamamatsu (27%), 3DHistech (10%), and Leica (7%). Regions of interest …

Premalignant Progression In The Lung: Knowledge Gaps And Novel Opportunities For Interception Of Non-Small Cell Lung Cancer An Official American Thoracic Society Research Statement, Seyed Javad Moghaddam, Rajkumar Savai, Ramin Salehi-Rad, Shreoshi Sengupta, Michael N Kammer, Pierre Massion, Jennifer E Beane, Edwin J Ostrin, Carmen Priolo, Meredith A Tennis, Laura P Stabile, Alison K Bauer, Catherine R Sears, Eva Szabo, M Patricia Rivera, Charles A Powell, Humam Kadara, Brendan J Jenkins, Steven M Dubinett, A Mcgarry Houghton, Carla F Kim, Robert L Keith

Faculty, Staff and Student Publications

Rationale: Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of cancer death worldwide. To reduce incidence and improve survival rates, a deeper understanding of lung premalignancy and the multistep process of tumorigenesis is essential, allowing timely and effective intervention before cancer development. Objectives: To summarize existing information, identify knowledge gaps, formulate research questions, prioritize potential research topics, and propose strategies for future investigations into the premalignant progression in the lung. Methods: An international multidisciplinary team of basic, translational, and clinical scientists reviewed available data to develop and refine research questions pertaining to the …

A Pilot Study Of The Cd38 Antagonist Daratumumab In Patients With Metastatic Renal Cell Carcinoma Or Muscle-Invasive Bladder Cancer, Matthew T Campbell, Amishi Y Shah, Pavlos Msaouel, Nizar M Tannir, Arlene O Siefker-Radtke, Ashish M Kamat, Neema Navai, Colin P N Dinney, Priya Rao, Charles C Guo, Rahul A Sheth, Aradhana M Venkatesan, Rebecca S Tidwell, Shalini S Yadav, Aidi Gu, Hong Chen, Marc Macaluso, Fei Duan, Sreyashi Basu, Sonali Jindal, Padmanee Sharma

Faculty, Staff and Student Publications

PURPOSE: We performed a pilot study of daratumumab (an mAb directed against CD38) in muscle-invasive bladder cancer (MIBC) and treatment-refractory metastatic renal cell carcinoma (mRCC).

EXPERIMENTAL DESIGN: Patients with MIBC underwent baseline transurethral resection of the bladder tumor followed by four weekly doses of daratumumab prior to cystectomy. Patients with mRCC underwent baseline and sequential biopsies after eight weekly doses. The primary endpoint was safety. The secondary endpoints were pathologic complete response rate for the MIBC cohort and objective response rate and progression-free survival for the mRCC cohort. Exploratory analyses included immune monitoring and overall survival. A Bayesian sequential monitoring …

Mechanisms That Clear Mutations Drive Field Cancerization In Mammary Tissue, Marta Ciwinska, Hendrik A Messal, Hristina R Hristova, Catrin Lutz, Laura Bornes, Theofilos Chalkiadakis, Rolf Harkes, Nathalia S M Langedijk, Stefan J Hutten, Renée X Menezes, Jos Jonkers, Stefan Prekovic, Grand Challenge Precision Consortium, Benjamin D Simons, Colinda L G J Scheele, Jacco Van Rheenen

Faculty, Staff and Student Publications

Oncogenic mutations are abundant in the tissues of healthy individuals, but rarely form tumours1-3. Yet, the underlying protection mechanisms are largely unknown. To resolve these mechanisms in mouse mammary tissue, we use lineage tracing to map the fate of wild-type and Brca1-/-;Trp53-/- cells, and find that both follow a similar pattern of loss and spread within ducts. Clonal analysis reveals that ducts consist of small repetitive units of self-renewing cells that give rise to short-lived descendants. This offers a first layer of protection as any descendants, including oncogenic mutant cells, are constantly lost, thereby limiting the spread of mutations to …

Cease The Alarms - A Nurse-Led Bundled Approach To Alarm Management, Annie Tolliver

EBP Fellowship

No abstract provided.