Digital Commons Network^™

Comparison Of The Mars And Xgboost Algorithms For Predicting Body Weight In Kalahari Red Goats, Louis Thobela Tyasi, Cem Tirink, Kwena Mokoena, Hasan Önder, Uğur Şen, Demet Çanga Boğa, Tolga Tolun, İsmai̇l Gök, Yüksel Aksoy, Lütfi̇ Bayyurt, Ömer Faruk Yilmaz

Turkish Journal of Veterinary & Animal Sciences

Estimating goat body weight from morphometric traits is essential for growth monitoring, health management, and welfare. Accurate weight informs nutrition, clinical interventions, and mating decisions. In this study, the MARS and XGBoost algorithms were used to estimate the live weight of Kalahari Red goats based on body measurements. A dataset containing body length (BL), birth type (single, twin, or triplet), withers height (WH), rump height (RH), and heart girth (HG) information for 200 goats was used in the training and testing of the models. The performances of the models were evaluated with the goodness-of-fit criteria. XGBoost showed a performance of …

Determination Of Cortisol Concentrations Using Different Biomarkers In Dairy Goats During Pregnancy, Fatma Mi̇ra Güven, Erkan Pehli̇van

Turkish Journal of Veterinary & Animal Sciences

Pregnancy is considered one of the most physiologically stressful periods in mammals. In the present study, serum and hair cortisol concentrations were measured in nine female Akkeçi goats, including five primiparous (1.5 years old) and four multiparous (3.5 years old), to evaluate chronic stress during pregnancy. Hair samples were collected in October, November, and December following the introduction of bucks to the herd and within the first 12 h postpartum (corresponding to the 1st, 2nd, 3rd, and 7th sampling times). Hair samples were not collected in January, February, or March (the 4th, 5th, and 6th sampling times) due to insufficient …

Effects Of Zinc-Reinforced Clinoptilolite On Hematological Parameters, Igg Levels, And Enzyme Histochemistry In Fattening Lambs, İhsan Kisadere, Muhi̇tti̇n Zengi̇n, Özkan Demi̇rbaş, Mehmet Faruk Aydin

Turkish Journal of Veterinary & Animal Sciences

The study aimed to determine the effects of zinc-reinforced clinoptilolite supplementation to the diet on selected hematological parameters, serum immunoglobulin G (IgG) concentrations, and enzyme histochemical characteristics in fattening lambs. For this purpose, 40 healthy male lambs were randomly allocated into five equal groups: control (C; n = 8), natural clinoptilolite (NC; n = 8), zinc (ZN; n = 8), natural clinoptilolite plus zinc (NCZN; n = 8), and zinc-reinforced clinoptilolite (ZNRC; n = 8). All animals were housed in individual pens, and the supplementation period continued for 42 days. Blood samples were collected before the trial (day 0) and …

Hatchability And Nestling Viability In An Extremely Short-Beaked Pigeon Breed, Türker Savaş, Hakan Erdem, Cemi̇l Tölü

Turkish Journal of Veterinary & Animal Sciences

The selection of hobby animals for breeding by enthusiasts is often based on aesthetic considerations, which can have a negative impact on the animals’ biology. Furthermore, “extreme traits” that deviate from ancestral norms, such as short beaks in pigeons, can be detrimental to the animal’s welfare. Beaks perform many essential functions, such as facilitating feed intake and eggshell breaking. The present study investigates possible hatching problems and the nestling viability of short-beak pigeons through a study of the breeding records of Mısıri (short beak), Baska (medium beak), and Turkish Dönek (normal beak) pigeons, as well as data from one breeding …

Comparing Anatomical Imaging With Functional Imaging For Coronary Artery Disease: The Limitations Of Vessel Stenosis And The Benefits Of Non-Invasive Measurement Of Fractional Flow Reserve, Zachary Zajac, Laura Aravena, Madeline Simone, David R. Allen Lll, Pranally Desai, Chanel Harvey, Nolan Tews, Nickolas Vinokurov

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising

Neglia D, Rovai D, Caselli C, Pietila M, Teresinska A, Aguadé-Bruix S, et al. Detection of Significant Coronary Artery Disease by Noninvasive Anatomical and Functional Imaging. Circ: Cardiovascular Imaging. 2015;8(3):e002179. https://doi.org/10.1161/CIRCIMAGING.114.002179

for a stable hospitalized patient admitted for acute coronary syndrome (ACS) rule out.

Microbiome-Responsive Hydrogels: From Biological Cues To Smart Biomaterials, Rajesh Vadlapatla, Amir Nasrolahi Shirazi, Ajoy Koomer, Judy Weng, Matthew Ernest Ghilarducci, Alai Qudus, Keykavous Parang

Pharmacy Faculty Articles and Research

Background: Stimuli-responsive hydrogels (SRHs) are smart polymeric materials that undergo reversible physicochemical changes in response to abiotic cues and externally applied fields, enabling applications in drug delivery, wound healing, and tissue engineering. However, they exhibit limited biological specificity and do not adequately reflect the dynamic, disease-relevant complexity of native tissue microenvironments. Microbe-colonized tissues display distinctive biochemical features driven, shaped by microbial metabolism, including localized pH gradients, short-chain fatty acid production, secretion of quorum-sensing molecules, biofilm formation, and expression of specialized enzymes. These endogenous, spatiotemporally regulated signals are closely linked to host physiology and pathology but remain underutilized in hydrogel …

Evidentiary Standards For Newly Approved Antibiotics For Uncomplicated Urinary Tract Infections, Rosa Rodriguez-Monguio, Enrique Seoane-Vazquez, John H. Powers Iii

Pharmacy Faculty Articles and Research

Importance: Uncomplicated urinary tract infections (uUTIs) are among the most common bacterial infections and are typically treated with existing oral antibiotics. In 2024–2025, the FDA approved two new oral agents, sulopenem etzadroxil/probenecid and gepotidacin, via expedited review pathways, for the treatment of uUTIs. Objective: To assess the clinical significance and regulatory evidence supporting FDA approval of sulopenem/probenecid and gepotidacin for uUTI, and to analyze the adherence of pivotal phase III trials to regulatory standards for approval and FDA guidelines. Design, Setting, and Participants: Comparative descriptive analysis of publicly available data from phase 3 randomized, double-blind, active-controlled clinical …

Zinc Imbalance And Its Effect On Nutritional Status, Behavior, Gut Microbiota, And Inflammatory Biomarkers In Btbr T+Itpr3tf/J And C57bl/6j Mice: Insights Into Autism Spectrum Disorder, Asma Nasrullah Ahmadani

Thesis/ Dissertation Defenses

Background: Autism spectrum disorder (ASD) has been associated with altered zinc homeostasis and disruptions in the gut microbiota. Zinc is a vital trace mineral involved in multiple biological processes such as inflammatory regulation, intestinal integrity, and neurobehavioral function, and has an important role in influencing microbial activity along the gut–brain axis. Both deficiency and excess of zinc can alter microbial balance. However, their collective effects on behavior, overall physiology, and mineral status in ASD-relevant models are not yet fully understood.

Aim: This comprehensive study explored the effect of dietary zinc variation on body weight, food intake, behavior, gut microbiota composition, …

Hybrid Vision Transformer–Cnn Framework For Alzheimer’S Disease Cell Type Classification: A Comparative Study With Vision–Language Models, Md Easin Hasan, Md Tahmid Hasan Fuad, Omar Sharif, Amy Wagler

School of Mathematical & Statistical Sciences Faculty Publications

Accurate identification of Alzheimer’s disease (AD)-related cellular characteristics from microscopy images is essential for understanding neurodegenerative mechanisms at the cellular level. While most computational approaches focus on macroscopic neuroimaging modalities, cell type classification from microscopy remains relatively underexplored. In this study, we propose a hybrid vision transformer–convolutional neural network (ViT–CNN) framework that integrates DeiT-Small and EfficientNet-B7 to classify three AD-related cell types—astrocytes, cortical neurons, and SH-SY5Y neuroblastoma cells—from phase-contrast microscopy images. We perform a comparative evaluation against conventional CNN architectures (DenseNet, ResNet, InceptionNet, and MobileNet) and prompt-based multimodal vision–language models (GPT-5, GPT-4o, and Gemini 2.5-Flash) using zero-shot, few-shot, and chain-of-thought …

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

Department of Medical Oncology Faculty Papers

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

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

Faculty, Staff and Student Publications

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

Outcomes Of Radiation Integrated With T-Cell-Engaging Bispecific Antibodies In Relapsed/Refractory Multiple Myeloma, Heta Patel, Harper Hubbeling, Kyle Yu, Maribel Carpenter, Michael Lariviere, John Plastaras, Adam Cohen, Shivani Kapur, Dan Vogl, Adam Waxman, Edward Stadtmauer, Alfred Garfall, Sandra Susanibar-Adaniya

Student Papers, Posters & Projects

No abstract provided.

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

Faculty, Staff and Student Publications

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

Liposclerosing Myxofibrous Tumor Of The Foot: A Case Report, Mohammad Junayed Khan, Sufiyan Mannan Ahmed, Asad Mustafa, Sairah Asghar, Mohammad Tanjim Hossain

School of Podiatric Medicine - Student Research

Statement of Purpose: This case presents a rare sclerosing-type atypical lipomatous tumor with myxomatous features—the first and only known reported case of an ALT in the foot—along with its pathology, treatment, and management.

Case Study: Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) represents the most common liposarcoma subtype, with recurrence and dedifferentiation risk influenced by tumor location. Retroperitoneal tumors recur frequently, while those in the lower extremity rarely do. Liposarcoma of the foot is exceedingly rare.

A 61-year-old male presented with a slowly enlarging, mildly tender lump on the right plantar heel. Radiographs demonstrated a 3 cm oval soft-tissue thickening without calcification. …

Midfoot Reconstruction For Avascular Necrosis Of The Navicular Bone​, Jessica Sima, Srilalitha Lanka, Merlin Sajeev, Shannon Rush, Graham Hamilton

School of Podiatric Medicine - Student Research

Background: Avascular necrosis (AVN) of the tarsal navicular, particularly with collapse, presents a complex surgical challenge due to compromised vascularity and the need to restore medial column length. This retrospective case series evaluates three distinct surgical approaches to midfoot reconstruction in patients with navicular AVN.

Methods: Three patients with navicular AVN were treated using individualized grafting strategies. Etiologies included chronic protease inhibitor use for HIV, Müller-Weiss syndrome, and post-resection of a giant cell tumor. All procedures utilized a medial utility incision with debridement to viable bleeding bone. Two cases were reconstructed using a combination of proximal tibial autograft, patellar allograft, …

Removing Race From Clinical Algorithms: History, Politics, And Medicine, David S. Jones Md, Ph.D.

History of Medicine Seminar

No abstract provided.

Innovative Approaches For Lung Cancer Screening And Interception, Jianjun Zhang, Matthew D Park, Tej Pandya, Elaine Shum, Jia Wu, Simon Heeke, Ramin Salehi-Rad, Thomas U Marron, Zhubo Wei, Hui Li, Torsten G Blum, John V Heymach, Steven M Dubinett, Pan-Chyr Yang, Charles Swanton, Miriam Merad

Faculty, Staff and Student Publications

Lung cancer remains the leading cause of cancer-related deaths worldwide, partly because many patients are diagnosed at late stages, highlighting the urgent need for effective early detection and intervention strategies. Low-dose computed tomography (LDCT)-based screening reduces lung cancer mortality in high-risk populations defined by age and smoking history; however, the uptake of LDCT remains low among eligible individuals. Compounding this issue, modelling studies estimate that nearly half of lung cancers occur in individuals who do not meet eligibility criteria for LDCT-based lung cancer screening under current guidelines. Moreover, LDCT-based screening has inherent limitations, including a high rate of false-positive results …

Supt16h-Associated Neurodevelopmental Disorder And Neurocristopathy: Genetic And Phenotypic Spectrum, Eunhye Lee, Seungmin Sim, Hee-Jung Choi, Eugene Y Liang, Carolyn Le, Roya Bina, Ryan Cohen, Elizabeth George, Soo Yeon Kim, Gifty Bhat, Erin Falsey, Richard Sidlow, Kristin Clinard, Shay Ben-Shachar, Eleina England, Beatriz Menendez, Isabella Herman, Shelly Nielsen, Jaya Punetha, Priya Bhola, J Austin Hamm, Megan A Keeney, Nike Sitzman, Sara Berger, Lakshmi Mehta, Alison J Conn, Lilian Downie, Myla Ashfaq, Hope Northrup, Ange-Line Bruel, Sylvie Odent, Justin O Szot, Noelia Nunez Martinez, Sunju Park, Julie Refkin, Jean-Marc Good, Fabienne Maurer, Cédric Le Caignec, David J Coman, Erin Anderson, Linda J Richards, Ryan J Dean, Caleb Yang, Chulwon Choi, Byung Joon Hwang, Jin Sook Lee, William B Dobyns, Murim Choi, Elliott H Sherr, Jong-Hee Chae, Yun Kee, Emanuela Argilli

Faculty, Staff and Student Publications

SUPT16H encodes a subunit of the FACT (FAcilitates Chromatin Transcription) complex, a histone chaperone essential for maintaining chromatin integrity during transcription, replication, and DNA repair. Pathogenic de novo SUPT16H missense variants have previously been linked to neurodevelopmental disorders in eight individuals. Here, we expand the genotypic and phenotypic spectrum by identifying 24 additional individuals harboring ultrarare heterozygous missense or truncating variants, who share overlapping clinical features including intellectual disability, autism spectrum disorder, hypotonia, and characteristic craniofacial dysmorphism. To elucidate the underlying mechanisms, we generated a supt16h knockout zebrafish model using CRISPR/Cas9. The supt16h loss-of-function (LOF) model recapitulated key patient phenotypes …

Do Body Composition And Cardiovascular Fitness Differ By Gender In Firefighters?, Giuliet L. Kibler, Kelly Hines, Michael J. Conner, Lisa C. Colvin, Steven E. Martin, Drew E. Gonzalez

International Journal of Exercise Science: Conference Proceedings

Firefighters (FF) endure substantial cardiovascular stress during their occupational tasks; yet, males and females differ in cardiovascular fitness (CRF) due to biological factors. The differences in body composition (BC) and CRF among FFs remain unclear. PURPOSE: To compare gender-specific outcomes in body BC and cardiopulmonary exercise test (CPET) of FF. METHODS: BC assessments via BIA and CPET on a cycle ergometer for 509 FF were analyzed from annual clinical testing. Gender was self-reported as follows: female (n = 29), male (n = 476), or other (n = 4). BC metrics, including body fat, lean body mass, skeletal muscle …

Evaluation Of Bone Turnover Markers And Biochemical Analysis In Developmental Metabolic Bone Diseases In Pediatric Aksaray Malakli Breed Dogs, Nihan Avci, Fehmiye Gumus Ozdil, Basak Boztok Ozgermen

The Thai Journal of Veterinary Medicine

Pediatric dogs are predisposed to skeletal disorders during growth, with rickets, hypertrophic osteopathy, and nutritional secondary hyperparathyroidism being the most common. Rickets, usually caused by vitamin D deficiency, leads to bone softening and deformities, whereas hypertrophic osteopathy involves abnormal calcium salt deposition that impairs mobility. This study investigated developmental orthopedic diseases in Aksaray Malakli dogs, focusing on nutritional factors and biochemical markers. Twenty-two pediatric dogs were examined and divided into two groups. Group I (n=11) showed gait abnormalities and postural deformities, whereas Group II (n=11) included clinically healthy dogs. Clinical, radiographic, and biochemical assessments were performed, including cortical index, parathormone, …

Adalimumab Therapy For Crohn’S Disease And Axial Spondyloarthritis In Latent Tuberculosis: A Bibliometric-Systematic Literature Review, Nyimas Maida Shofa, Nurike Setiyari Mudjari, Rusdiyana Ekawati, Arianti Arianti, Annisa Zahra Mufida, Budi Widodo, Titong Sugihartono

Sultan Qaboos University Medical Journal

The management of Crohn’s disease (CD) using anti-tumour necrosis factor therapy in tuberculosis (TB)-endemic regions poses major clinical challenges due to the risk of latent TB infection reactivation. This bibliometric–systematic literature review synthesised evidence from 17 peer-reviewed studies (2020–2025) evaluating adalimumab administered with concurrent prophylactic antitubercular therapy. Thematic synthesis and bibliometric mapping using VOSviewer demonstrated that adalimumab achieved 60–85% clinical remission in moderate-to-severe CD and axial spondyloarthritis while enhancing mucosal healing. However, 1–3% of patients developed active TB despite appropriate screening and isoniazid prophylaxis, revealing false-negative diagnostics and partial chemoprophylaxis protection. These findings highlight the need for region-specific frameworks integrating …

Advances In Hpv Vaccination In People Living With Hiv: A Review, Megan Mooberry, J Brooks Jackson, Mary B Rysavy

Faculty, Staff and Student Publications

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and is a leading cause of cervical, anal, penile, and oropharyngeal cancers. This review summarizes the epidemiology of HPV and the immunogenicity, clinical efficacy, and current HPV vaccination recommendations among people living with HIV (PLWH). PLWH experience a disproportionate burden of HPV-related infection and HPV-related malignancies. Although HPV vaccines have been shown to be highly effective, vaccination coverage among PLWH remains suboptimal, particularly in low- and middle-income countries. Barriers to vaccination include extended dosing schedules, limited awareness of the vaccine, and misinformation. Evidence indicates HPV vaccines are safe and …

Airway Secretory Cells Contain Both A Perinuclear Golgi Ribbon And Dispersed Golgi Satellites, Oanh N Hoang, Colin E Chan, Joshua M Brenner, Denisse Leza-Rincon, Ana M Jaramillo, Brendan Dolan, Adam W Aziz, Rodolfo A Cardenas, Gerardo J Cardenas, Eduardo D Galvez, Joshua B Hales, Emilia S Nunez-Pena, Boxuan Yang, Reid T Powell, Leoncio Vergara, Harry Karmouty-Quintana, Jesper M Magnusson, Gunnar C Hansson, Roberto Adachi, John D Dickinson, Christopher M Evans, Justin A Courson, Alan R Burns, Michael J Tuvim, Burton F Dickey

Faculty, Staff and Student Publications

Rationale: Finely tuned production and secretion of the polymeric mucins MUC5AC and MUCB are required for lung health, but knowledge of many details between their translation and their packaging into secretory granules is lacking.

Objective: To analyze the structure and function of the Golgi apparatus, a key site of mucin glycosylation, folding, polymerization and packaging, in airway epithelial secretory cells.

Methods: Lung tissue was obtained from mice stimulated or not with IL-13 to upregulate mucin production, and from normal human lungs. Golgi elements in mouse and human tissue were imaged by high-resolution immunofluorescence microscopy and electron microscopy. Tissue from mice …

Gender Differences In College Students’ Physical Activity Self-Efficacy, Social Comparison Beliefs, And External Frames Of Reference, Ken Murfay, Sarah Pyszczynski, Sarah Collins

International Journal of Physical Activity and Health

This study examined whom college-aged individuals believe observing would more likely increase their physical activity self-efficacy (PASE) for a physical skill, whom they are more likely to compare their abilities to within a physical education (PE) class, how often they compare themselves to others in PE, and what students’ PASE scores were. Based on the mean scores for each question, students were more likely to compare themselves to a student than a teacher, friend than a non-friend, and similar or higher skilled peer than a lower skilled peer. To increase students’ confidence for a physical skill, students had higher levels …

Human Microglia In Brain Assembloids Display Region-Specific Diversity And Respond To Hyperexcitable Neurons Carrying Scn2a Mutation, Jiaxiang Wu, Xiaoling Chen, Jingliang Zhang, Kyle Wettschurack, Morgan Robinson, Weihao Li, Yuanrui Zhao, Ye-Eun Yoo, Brody A Deming, Yue Shu, Akila D Abeyaratna, Zhefu Que, Dongshu Du, Matthew Tegtmeyer, Chongli Yuan, William C Skarnes, Zhong-Yin Zhang, Jean-Christophe Rochet, Long-Jun Wu, Yang Yang

The Brown Foundation: Institute of Molecular Medicine

Microglia critically shape neuronal circuit development and function, yet their region-specific properties and roles in distinct circuits of the human brain remain poorly understood. In this study, we generated region-specific brain organoids (cortical, striatal, and midbrain), each integrated with human microglia, to fill this critical gap. Single-cell RNA sequencing uncovered six distinct microglial subtypes exhibiting unique regional signatures, including a subtype highly enriched for the GABAB receptor gene within striatal organoids. To investigate the contributions of microglia to neural circuitry, we created microglia-incorporated midbrain-striatal assembloids, modeling a core circuit node for many neuropsychiatric disorders, including autism. Using chemogenetics to activate …

Association Between Children’S Secondhand Co-Exposure To Tobacco And Cannabis Smoke And Elevated Urinary Cotinine Levels: A Cross-Sectional Analysis, Bradley N. Collins, Stephen J. Lepore, Vincent Berardi, Renee D. Goodwin, Karen Wilson, Mona Baishya

Psychology Faculty Articles and Research

Background Cannabis use is far more common among adults who smoke tobacco than adults who do not, and its use is increasing among people who smoke tobacco with children living in the home. Given the well-established evidence that caregiver smoking is the primary source of children’s secondhand exposures to these products, the increasing trend in caregiver co-use is raising public health concerns about children’s co-exposure. Emerging data indicates that adult co-use is linked to additive health consequences, such as elevated nicotine and other tobacco-related toxicant blood levels, relative to use of only tobacco. It is unknown whether children’s co-exposure leads …

External Validation Of The Proliferation Saturation Index Model In Predicting Tumour Volume Regression In Patients With Non-Small Cell Lung Cancer Undergoing Radiation Therapy, Sarah Barrett, Mohammad Zahid, Conor K Mcgarry, Heiko Enderling, Gerard M Walls, Laure Marignol

Faculty, Staff and Student Publications

Background: The Proliferation Saturation Index (PSI) model is a patient-specific mathematical model designed to simulate and predict tumour volume regression (TVR) during radiation therapy (RT) using early treatment response dynamics. This study validates the PSI model in an independent external cohort of patients with non-small cell lung cancer (NSCLC) using previously derived model parameters.

Methods: In a cohort of 71 patients, treated with definitive RT alone (55Gy/20#) tumour volume measurements extracted from 6 Cone Beam CT (CBCT) scans acquired on days 1, 2 and 3 and weekly thereafter. Model predictions of TVR at final CBCT (CBCT6) were made using tumour …

Hp1Β Recruits Ring1a To Ubiquitinate Histone H2a For Brca1-Mediated Resection Of Double-Stand Breaks, Vijaya Charaka, Raj K Pandita, Chi-Lin Tsai, Xiaoyan Wang, Sharmista Chakraborty, Kenneth S Ramos, Sandhik Nandi, Fransisca Leonard, Vipin Singh, Partha S Sarkar, Clayton R Hunt, John A Tainer, Chandrima Das, Tej K Pandita

Faculty, Staff and Student Publications

Efficient DNA double-strand break (DSB) repair by homologous recombination (HR), as initiated by BRCA1 recruitment orchestrated by histone and non-histone proteins, is critical to genome stability, replication, transcription, and cancer avoidance. Here we reveal Heterochromatin Protein1 beta (HP1β) promotes BRCA1 enrichment at DNA DSB sites in gene-rich regions, and this is impaired by HP1β depletion. We find that HP1β is specifically enriched at DSBs within gene-rich regions via its Chromo Shadow Domain (CSD) that interacts with both Chromatin Assembly Factor 1 and the RING1A ubiquitinase component of Polycomb Repressor Complex 1. The resulting protein complex facilitates BRCA1 recruitment by promoting …

Nci9673 (Part B): Etctn Randomized Phase Ii Study Of Nivolumab With Or Without Ipilimumab In Refractory, Metastatic Squamous Cell Carcinoma Of The Anal Canal, Van K Morris, Kristen K Ciombor, Lianchun Xiao, Joshua K Ochieng, Enrica Marmonti, Blase Polite, Benjamin A Weinberg, John C Krauss, John Hays, Sarbajit Mukherjee, Olivia Aranha, Syma Iqbal, Tony Shields, Al B Benson, Syed Kazmi, Christopher Lieu, Howard Hochster, Jennifer Whisenant, Cara Haymaker, Cathy Eng

Faculty, Staff and Student Publications

Purpose: In the previously completed NCI9673 (part A) single-arm study, the antiprogrammed death (PD)-ligand-1 antibody nivolumab demonstrated efficacy for patients with metastatic anal cancer. In NCI9673 (Part B), we evaluated the anticytotoxic T-cell lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in combination with nivolumab for patients with incurable anal cancer.

Methods: In this phase II NCI ETCTN trial, 100 patients with refractory, incurable anal cancer were randomly assigned to receive nivolumab (480 mg IV once every 4 weeks) alone or with ipilimumab (1 mg/kg IV once every 8 weeks). The primary end point was progression-free survival (PFS). Secondary endpoints included radiographic response, …

Steroid Receptor Coactivators - From Basic Research To Translational Opportunities, Yosef Gilad, Sang Jun Han, David M Lonard

Faculty, Staff and Students Publications

The concept of nuclear receptor (NR) coregulation was proposed nearly two decades before it was experimentally validated. According to this model, NRs - executors of a vast array of transcriptional programs - do not act independently but are governed by a network of regulatory proteins that either activate or repress their biological function. NRs identify the genes to be regulated. However, coregulators ultimately serve as the true controllers of transcriptional outcomes. They recruit cofactors and coordinate the activity of transcriptional complexes, thereby shaping NR-mediated gene expression beyond NRs' intrinsic functionality. The Steroid Receptor Coactivator (SRC) family is the most extensively …