Medical Specialties Commons^™

Development Of An Online Authentic Radiology Viewing And Reporting Platform To Test The Skills Of Radiology Trainees In Low- And Middle-Income Countries, Hubert Vesselle, Justy Antony Chiramal, Stephen Hawes, Eric Schulze, Tham Nguyen, Rose Ndumia, Sudhir Vinayak

Imaging & Diagnostic Radiology, East Africa

Background: Diagnostic radiology residents in low- and middle-income countries (LMICs) may have to provide significant contributions to the clinical workload before the completion of their residency training. Because of time constraints inherent to the delivery of acute care, some of the most clinically impactful diagnostic radiology errors arise from the use of Computed Tomography (CT) in the management of acutely ill patients. As a result, it is paramount to ensure that radiology trainees reach adequate skill levels prior to assuming independent on-call responsibilities. We partnered with the radiology residency program at the Aga Khan University Hospital in Nairobi (Kenya) to …

Angle Accuracy Of Intramedullary Bone Resection Guides For Total Knee Arthroplasty., Matthew C Kane, Harold E Cates, Iou-Ren Chang

Surgery Articles

The importance of proper prosthetic placement has been confirmed in numerous studies. The objective of this study was to compare the planned resection angles to the verified intraoperative angles of femoral and tibial varus/valgus, tibial slope, and femoral flexion for each total knee performed using intramedullary (IM) cut guides for both distal femur and proximal tibia cuts. A total of 1,000 total knee arthroplasties (TKAs) were evaluated for this study. Intraoperative cut-check technology was used to show real-time validation of these resection angles. Assuming an acceptable range of within 2° of the planned cuts, results show the femoral varus/valgus angles …

Dominant Missense Variants In Srebf2 Are Associated With Complex Dermatological, Neurological, And Skeletal Abnormalities, Matthew J Moulton, Kristhen Atala, Yiming Zheng, Debdeep Dutta, Dorothy K Grange, Wen-Wen Lin, Daniel J Wegner, Jennifer A Wambach, Angela L Duker, Michael B Bober, Lisa Kratz, Carol A Wise, Ila Oxendine, Anas Khanshour, Undiagnosed Diseases Network, Michael F Wangler, Shinya Yamamoto, F Sessions Cole, Jonathan Rios, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Purpose: We identified 2 individuals with de novo variants in SREBF2 that disrupt a conserved site 1 protease (S1P) cleavage motif required for processing SREBP2 into its mature transcription factor. These individuals exhibit complex phenotypic manifestations that partially overlap with sterol regulatory element binding proteins (SREBP) pathway-related disease phenotypes, but SREBF2-related disease has not been previously reported. Thus, we set out to assess the effects of SREBF2 variants on SREBP pathway activation.

Methods: We undertook ultrastructure and gene expression analyses using fibroblasts from an affected individual and utilized a fly model of lipid droplet (LD) formation to investigate the consequences …

Enhancement Of High-Density Lipoprotein-Associated Protease Inhibitor Activity Prevents Atherosclerosis Progression, Maura Mobilia, Alexander A. Karakashian, Khaga R. Neupane, Olivia Hage, Callie Whitus, Abigail Carter, Clairity Voy, Lance A. Johnson, Gregory A. Graf, Scott M. Gordon

Saha Cardiovascular Research Center Faculty Publications

Background and aims: Inflammatory cells within atherosclerotic lesions secrete proteolytic enzymes that contribute to lesion progression and destabilization, increasing the risk for an acute cardiovascular event. Elastase is a serine protease, secreted by macrophages and neutrophils, that may contribute to the development of unstable plaque. We previously reported interaction of endogenous protease-inhibitor proteins with high- density lipoprotein (HDL), including alpha-1-antitrypsin, an inhibitor of elastase. These findings support a potential role for HDL as a modulator of protease activity. In this study, we test the hypothesis that enhancement of HDL-associated elastase inhibitor activity is protective against atherosclerotic lesion progression.

Methods: We …

Centring Youth Mental Health Discourse On Low-Income And Middle-Income Countries, Kelly Rose-Clark, Mary Bitta, Evans-Lacko Sara, Jokinen Tahir, Mark Jordans, Moses Nyongesa, Abhijit Nadkarn, Praveetha Patalay, Indira Pradhan, Atif Rahman

Brain and Mind Institute

Commentwww.thelancet.com/psychiatry Vol 11 September 2024 671 The Lancet Psychiatry Commission on Youth Mental Health heralds a new field of research and practice with a focus on people aged 12–25 years.1 Patrick D McGorry and colleagues assert the global relevance of the field while acknowledging that much of its underpinning evidence comes from high-income countries (HICs). This distribution is problematic because 90% of children and adolescents live in low-income and middle-income countries (LMICs), which are under- represented academically and yet have the highest burden of mental ill health. Extrapolating findings from HICs to LMICs ignores crucial diversity in young people’s socioeconomic …

Utilization Of Blood Flow Restriction Therapy With A Former Triathlete After Total Knee Arthroplasty: A Case Report, Christopher Keating, Stephanie Muth, Pt, Phd, Cameron Hui, Lisa T. Hoglund

Department of Physical Therapy Faculty Papers

INTRODUCTION AND PURPOSE: Knee osteoarthritis (OA) is a common condition that limits function and reduces quality of life. Total knee arthroplasty (TKA) is a surgical procedure that replaces the joint surfaces to address anatomical changes due to knee OA. While TKA improves symptoms and function, postoperative impairments are common, including reduced quadriceps strength. Blood flow restriction (BFR) may be a viable option for patients following TKA, as it can improve strength with a minimal amount of joint loading compared to traditional strength training. The purpose of this case report is to describe the impact of BFR use in an individual …

Skin Necrosis Following Digital Wart Intralesional Injection Of Cantharidin, Sebastian Arango, Tristan Weir, Andrew Miller, Meredith Osterman

Department of Orthopaedic Surgery Faculty Papers

A right-hand-dominant female presented 5 weeks following a right middle finger intralesional cantharidin injection for a common wart by a dermatologist. The patient experienced progressive stiffness, blistering, swelling, pain, and ultimately, full-thickness skin necrosis surrounding the injection site. Careful debridement followed by a full-thickness skin graft was performed with no evidence of involvement of the germinal matrix or terminal extensor tendon. At the 7-month postoperative mark, the patient’s graft exhibited favorable healing and improved functionality that did not require further follow-up. Intralesional injection of cantharidin solutions for digital warts leads to progressive skin necrosis. Our case required prompt debridement and …

Analysis Of Patients Who Undergo Index Arthroscopy With Biopsy But Not Implantation For Staged Chondrocyte Cell Transplantation, Bryson R. Kemler, Emma E. Johnson, Brad M. Evert, Azra N. Dees, Alec M. Giakas, Adeeb Jacob Hanna, Taylor D'Amore, Kevin B. Freedman, Sommer Hammoud

Rothman Institute Papers

BACKGROUND: Autologous chondrocyte implantation (ACI) and matrix-induced autologous chondrocyte implantation (MACI) are 2-stage procedures requiring an index full-thickness cartilage biopsy. Only a portion of patients ultimately undergo second-stage ACI/MACI.

PURPOSE: To identify patients with articular cartilage defects who underwent arthroscopic debridement with biopsy for ACI/MACI and compare those who did with those who did not proceed with implantation within 2 years after biopsy. Additionally, the authors sought to identify why patients did not proceed with implantation.

STUDY DESIGN: Case-control study; Level of evidence, 3.

METHODS: Patients who underwent arthroscopy and autologous chondrocyte biopsy from January 1, 2015, to December 31, …

Endovascular Aneurysm Repair-First Strategy For Ruptured Abdominal Aortic Aneurysm Might Not Be Applicable To All Cases, Omkar Pawar, Anuja Sarode, Benjamin D. Colvard, Jae S. Cho

Faculty Scholarship

Background: We evaluate the relationship between the hospital case volume (HCV) and mortality outcomes after open aortic repair (OAR) and endovascular aortic repair (EVAR) of intact (iEVAR) and ruptured (rEVAR) abdominal aortic aneurysm (AAA) using a contemporary administrative database. Methods: The Healthcare Cost and Utilization Project Database for New York (2016) and New Jersey/Maryland/Florida (2016–2017) were queried using International Classification of Disease-10th edition to identify patients who had undergone OAR and EVAR. The hospitals were categorized into quartiles (Q) per overall (EVAR + OAR) volume, OAR-alone volume and EVAR-alone volume. Cox regression adjusted for confounding factors was used to estimate …

Association Of Glp-1 Receptor Agonists And Hepatocellular Carcinoma Incidence And Hepatic Decompensation In Patients With Type 2 Diabetes, Lindsey Wang, Nathan A. Berger, David C. Kaelber, Rong Xu

Faculty Scholarship

Background & aims: Hepatocellular carcinoma (HCC) is a leading cause of cancer death. HCC is preventable with about 70% of HCC attributable to modifiable risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), Food and Drug Administration–approved medications for treating type 2 diabetes mellitus (T2DM), have pleiotropic effects on counteracting risk factors for HCC. Here we evaluate the association of GLP-1RAs with incident HCC risk in a real-world population. Methods: This retrospective cohort included 1,890,020 patients with a diagnosis of T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications and had no prior diagnosis of HCC. Incident (first-time) diagnosis of HCC …

Perspectives On The Clinical Use Of Anti-Amyloid Therapy For The Treatment Of Alzheimer's Disease: Insights From The Fields Of Cancer, Rheumatology, And Neurology, Gregory Jicha, Erin Abner, Elif Pinar Coskun, Mark Huffmyer, Thomas Tucker, Peter T. Nelson

Neurology Faculty Publications

Introduction: The advent of disease-modifying therapies for Alzheimer’s disease (AD) has raised many questions and debates in the field as to the clinical benefits, risks, and costs of such therapies. The controversies have resulted in the perception that many clinicians are apprehensive about prescribing these medications to their patient populations. There also remains widespread uncertainty as to the economic impact, cost benefit ratio, and safety oversight for use of these medications in standard clinical care settings.

Methods: To contextualize such issues, the present study compared anti-amyloid biologic therapy (lecanemab) to four commonly used biologic agents in other fields, including trastuzumab …

The Seattle Amyotrophic Lateral Sclerosis (Als) Patient Project Database: Observational, Longitudinal, Dyadic Characterization Of People With Als And Their Partners, Suzanne C. Segerstrom, Edward J. Kasarskis

Neurology Faculty Publications

Introduction: The median survival time in ALS is approximately 3 years, but survival times range from less than a year to more than 10 years and much variance in disease course remains to be explained. As is true for physical outcomes, there is considerable variance in QOL, which is influenced by psychological health, coping, and social support, among other psychosocial factors. The Seattle ALS Patient Project Database (SALSPPD) provides a unique opportunity for researchers to address established and novel hypotheses about disease progression and QOL in ALS.

Methods: The SALSPPD is a longitudinal dataset of people with ALS (n = …

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 …

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 …

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

Conference Presentation Abstracts

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

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 …

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 …

Characterization Of High-Risk-Other Human Papillomavirus Genotypes In Papanicolaou Tests, High-Grade Squamous Intraepithelial Lesions, And Cervical Cancer, Caitlin E. Witt, Elizabeth F. Sutton, Ashley M. Stansbury, Ashley N. Winters, Luke C. Konur, Meng Luo, Jennifer E. Cameron, Beverly Ogden

School of Medicine Faculty Publications

Background: The objective of this study was to determine the human papillomavirus (HPV) genotypes of high-risk-other HPV Papanicolaou (Pap) tests and of biopsy tissues from patients with high-grade squamous intraepithelial lesion (HGSIL) or cervical cancer. High-risk-other HPV status was determined with the cobas HPV Test (Roche Diagnostics, North America) that identifies 12 high-risk, non-16/18 HPV genotypes. We hypothesized that we would find genotypes of HPV in our population that are not covered by the 9-valent HPV vaccine. Methods: For this retrospective cohort study, we randomly selected 50 high-risk-other HPV Pap test samples from 2018 from our pathology department registries for …

Return To Play Time After Achilles Tendon Rupture In Professional Soccer Players, Oyinkansola Mudasiru, Amanda Killeen

School of Podiatric Medicine - Student Research

Introduction: Achilles tendon ruptures are severe injuries that drastically affect the careers of athletes. These ruptures typically occur during matches, often due to dorsiflexion of the ankle during passes or when tackling. Professional athletes tend to have surgical repair quickly with the goal of returning to their sport as fast as possible.

Objective: To present a scoping review to identify the return to play (RTP) rates following Achilles tendon rupture and whether these athletes achieve functional outcomes comparable to their pre- operative conditions.

Methods: 2 databases were queried; Google Scholar and PubMed using the search terms "Achilles tendon rupture" AND …

Exploiting The Heavy Chain Glycans For The Improvement Of Radioimmunoconjugates, Cindy Rodriguez

Dissertations, Theses, and Capstone Projects

Radiolabeled antibodies have become indispensable tools in nuclear medicine. However, the natural roles of antibodies within the immune system mean that they have several intrinsic limitations as a platform for radiopharmaceuticals. A handful of recent preclinical studies suggest that binding by FcR and particularly FcyRI can affect the pharmacokinetic profiles of 89Zr-labeled radioimmunoconjugates. Fc receptors (FcR) are responsible for many of the interactions between immunoglobulins (IgG) and immune cells. In biomedicine, this interplay is critical to the activity of several types of immunotherapeutics; however, relatively little is known about how FcRs affect the in vivo performance of radiolabeled antibodies. Antibodies …