Digital Commons Network^™

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 …

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 …

Panel Stacking Is A Threat To Consensus Statement Validity, Kasper P Kepp, Preben Aavitsland, Marcel Ballin, Francois Balloux, Stefan Baral, Kevin Bardosh, Howard Bauchner, Eran Bendavid, Raj Bhopal, Daniel T Blumstein, Paolo Boffetta, Florence Bourgeois, Adam Brufsky, Peter J Collignon, Sally Cripps, Ioana A Cristea, Nigel Curtis, Benjamin Djulbegovic, Oliver Faude, Maria Elena Flacco, Gordon H Guyatt, George Hajishengallis, Lars G Hemkens, Tammy Hoffmann, Ari R Joffe, Terry P Klassen, Despina Koletsi, Dimitrios P Kontoyiannis, Ellen Kuhl, Carlo La Vecchia, Tea Lallukka, John Lambris, Michael Levitt, Spyros Makridakis, Helena C Maltezou, Lamberto Manzoli, Ana Marusic, Clio Mavragani, David Moher, Ben W Mol, Taulant Muka, Florian Naudet, Paul W Noble, Anna Nordström, Peter Nordström, Nikolaos Pandis, Stefania Papatheodorou, Chirag J Patel, Irene Petersen, Stefan Pilz, Nikolaus Plesnila, Anne-Louise Ponsonby, Manuel A Rivas, Andrea Saltelli, Manuel Schabus, Michaéla C Schippers, Holger Schünemann, Marco Solmi, Andreas Stang, Hendrik Streeck, Joachim P Sturmberg, Lehana Thabane, Brett D Thombs, Athanasios Tsakris, Simon N Wood, John P A Ioannidis

Faculty, Staff and Student Publications

Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members toward one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but nonfinancial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analyzing in depth a …

Metabolic Cell Death In Cancer: Ferroptosis, Cuproptosis, Disulfidptosis, And Beyond, Chao Mao, Min Wang, Li Zhuang, Boyi Gan

Faculty, Staff and Student Publications

Cell death resistance represents a hallmark of cancer. Recent studies have identified metabolic cell death as unique forms of regulated cell death resulting from an imbalance in the cellular metabolism. This review discusses the mechanisms of metabolic cell death-ferroptosis, cuproptosis, disulfidptosis, lysozincrosis, and alkaliptosis-and explores their potential in cancer therapy. Our review underscores the complexity of the metabolic cell death pathways and offers insights into innovative therapeutic avenues for cancer treatment.

Proteomic Analysis Of Ferroptosis Pathways Reveals A Role Of Cept1 In Suppressing Ferroptosis, Xiaoguang Liu, Zhen Chen, Yuelong Yan, Fereshteh Zandkarimi, Litong Nie, Qidong Li, Amber Horbath, Kellen Olszewski, Lavanya Kondiparthi, Chao Mao, Hyemin Lee, Li Zhuang, Masha Poyurovsky, Brent R Stockwell, Junjie Chen, Boyi Gan

Faculty, Staff and Student Publications

Ferroptosis has been recognized as a unique cell death modality driven by excessive lipid peroxidation and unbalanced cellular metabolism. In this study, we established a protein interaction landscape for ferroptosis pathways through proteomic analyses, and identified choline/ethanolamine phosphotransferase 1 (CEPT1) as a lysophosphatidylcholine acyltransferase 3 (LPCAT3)-interacting protein that regulates LPCAT3 protein stability. In contrast to its known role in promoting phospholipid synthesis, we showed that CEPT1 suppresses ferroptosis potentially by interacting with phospholipases and breaking down certain pro-ferroptotic polyunsaturated fatty acid (PUFA)-containing phospholipids. Together, our study reveals a previously unrecognized role of CEPT1 in suppressing ferroptosis.

Oric-101, A Glucocorticoid Receptor Antagonist, In Combination With Nab-Paclitaxel In Patients With Advanced Solid Tumors, Christopher T Chen, Vishesh Khanna, Shivaani Kummar, Raghad M Abdul-Karim, David Sommerhalder, Anthony W Tolcher, Naoto T Ueno, Sarah Lindsey Davis, Douglas W Orr, Erika Hamilton, Manish R Patel, Alexander I Spira, Shekeab Jauhari, Vaia Florou, Maureen Duff, Rongda Xu, Jian Wang, Shravani R Barkund, Haiying Zhou, Aleksandr Pankov, Wayne Kong, Nadine S Jahchan, Erica L Jackson, Jessica D Sun, Melissa R Junttila, Pratik S Multani, Anneleen Daemen, Edna Chow Maneval, Pamela N Munster

Faculty, Staff and Student Publications

Purpose: In preclinical models, glucocorticoid receptor (GR) signaling drives resistance to taxane chemotherapy in multiple solid tumors via upregulation of antiapoptotic pathways. ORIC-101 is a potent and selective GR antagonist that was investigated in combination with taxane chemotherapy as an anticancer regimen preclinically and in a phase 1 clinical trial.

Patients and methods: The ability of ORIC-101 to reverse taxane resistance was assessed in cell lines and xenograft models, and a phase 1 study (NCT03928314) was conducted in patients with advanced solid tumors to determine the dose, safety, and antitumor activity of ORIC-101 with nab-paclitaxel.

Results: ORIC-101 reversed …

Image-Guided Patient-Specific Optimization Of Catheter Placement For Convection-Enhanced Nanoparticle Delivery In Recurrent Glioblastoma, Chengyue Wu, David A Hormuth, Chase D Christenson, Ryan T Woodall, Michael R A Abdelmalik, William T Phillips, Thomas J R Hughes, Andrew J Brenner, Thomas E Yankeelov

Faculty, Staff and Student Publications

Background: Proper catheter placement for convection-enhanced delivery (CED) is required to maximize tumor coverage and minimize exposure to healthy tissue. We developed an image-based model to patient-specifically optimize the catheter placement for rhenium-186 (186Re)-nanoliposomes (RNL) delivery to treat recurrent glioblastoma (rGBM).

Methods: The model consists of the 1) fluid fields generated via catheter infusion, 2) dynamic transport of RNL, and 3) transforming RNL concentration to the SPECT signal. Patient-specific tissue geometries were assigned from pre-delivery MRIs. Model parameters were personalized with either 1) individual-based calibration with longitudinal SPECT images, or 2) population-based assignment via leave-one-out cross-validation. The concordance correlation coefficient …

Nanoscale Gold Nanoparticle (Gnp)-Laden Tumor Cell Model And Its Use For Estimation Of Intracellular Dose From Gnp-Induced Secondary Electrons, Sandun Jayarathna, Amrit Kaphle, Sunil Krishnan, Sang Hyun Cho

Faculty, Staff and Student Publications

Background: Gold nanoparticles (GNPs) accumulated within tumor cells have been shown to sensitize tumors to radiotherapy. From a physics point of view, the observed GNP-mediated radiosensitization is due to various downstream effects of the secondary electron (SE) production from internalized GNPs such as GNP-mediated dose enhancement. Over the years, numerous computational investigations on GNP-mediated dose enhancement/radiosensitization have been conducted. However, such investigations have relied mostly on simple cellular geometry models and/or artificial GNP distributions. Thus, it is at least desirable, if not necessary, to conduct further investigations using cellular geometry models that properly reflect realistic cell morphology as well as …

Smyd5 Is A Ribosomal Methyltransferase That Catalyzes Rpl40 Lysine Methylation To Enhance Translation Output And Promote Hepatocellular Carcinoma, Bisi Miao, Ling Ge, Chenxi He, Xinghao Wang, Jibo Wu, Xiang Li, Kun Chen, Jinkai Wan, Shenghui Xing, Lingnan Ren, Zhennan Shi, Shengnan Liu, Yajun Hu, Jiajia Chen, Yanyan Yu, Lijian Feng, Natasha M Flores, Zhihui Liang, Xinyi Xu, Ruoxin Wang, Jian Zhou, Jia Fan, Bin Xiang, En Li, Yuanhui Mao, Jingdong Cheng, Kehao Zhao, Pawel K Mazur, Jiabin Cai, Fei Lan

Faculty, Staff and Student Publications

While lysine methylation is well-known for regulating gene expression transcriptionally, its implications in translation have been largely uncharted. Trimethylation at lysine 22 (K22me3) on RPL40, a core ribosomal protein located in the GTPase activation center, was first reported 27 years ago. Yet, its methyltransferase and role in translation remain unexplored. Here, we report that SMYD5 has robust in vitro activity toward RPL40 K22 and primarily catalyzes RPL40 K22me3 in cells. The loss of SMYD5 and RPL40 K22me3 leads to reduced translation output and disturbed elongation as evidenced by increased ribosome collisions. SMYD5 and RPL40 K22me3 are upregulated in hepatocellular carcinoma …

Large Language Models For Biomedicine: Foundations, Opportunities, Challenges, And Best Practices, Satya S Sahoo, Joseph M Plasek, Hua Xu, Özlem Uzuner, Trevor Cohen, Meliha Yetisgen, Hongfang Liu, Stéphane Meystre, Yanshan Wang

Faculty, Staff and Student Publications

Objectives: Generative large language models (LLMs) are a subset of transformers-based neural network architecture models. LLMs have successfully leveraged a combination of an increased number of parameters, improvements in computational efficiency, and large pre-training datasets to perform a wide spectrum of natural language processing (NLP) tasks. Using a few examples (few-shot) or no examples (zero-shot) for prompt-tuning has enabled LLMs to achieve state-of-the-art performance in a broad range of NLP applications. This article by the American Medical Informatics Association (AMIA) NLP Working Group characterizes the opportunities, challenges, and best practices for our community to leverage and advance the integration of …

Ablative Margin Quantification Using Deformable Versus Rigid Image Registration In Colorectal Liver Metastasis Thermal Ablation: A Retrospective Single-Center Study, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Jun Hong, Ketan Y Shah, Mohamed E Abdelsalam, Peiman Habibollahi, Kyle A Jones, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Purpose: To investigate the correlation of minimal ablative margin (MAM) quantification using biomechanical deformable (DIR) versus intensity-based rigid image registration (RIR) with local outcomes following colorectal liver metastasis (CLM) thermal ablation.

Methods: This retrospective single-institution study included consecutive patients undergoing thermal ablation between May 2016 and October 2021. Patients who did not have intraprocedural pre- and post-ablation contrast-enhanced CT images for MAM quantification or follow-up period less than 1 year without residual tumor or local tumor progression (LTP) were excluded. DIR and RIR methods were used to quantify the MAM. The registration accuracy was compared using Dice similarity coefficient (DSC). …

The Geriatric Trauma Hospitalist Service: An Analysis Of A Management Strategy For Injured Older Adults, Heather R Kregel, Claudia Pedroza, Fatimah Sunez, Gina Khraish, Ezenwa Onyema, David E Meyer, Sasha D Adams, Lillian S Kao, Laura J Moore, Thaddeus J Puzio

Faculty, Staff and Student Publications

Background: Management of geriatric trauma patients requires balancing chronic comorbidities with acute injuries. We developed a care model in which patients are managed by hospitalists with trauma-centered education and hypothesized that clinical outcomes would be similar to outcomes in patients primarily managed by trauma surgeons.

Methods: This was a retrospective study of trauma patients aged ≥65 from January 2020 to December 2021. Groups were defined by admitting service: trauma surgery service (TSS) or geriatric trauma hospitalist service (GTHS). The primary outcome was in-hospital mortality. Regression analyses and inverse probability treatment weighted (IPTW) propensity score (PS) analyses were performed to determine …

Bioengineering Of Intestinal Grafts, Madushani Herath, Allison L Speer

Faculty, Staff and Student Publications

Intestinal failure manifests as an impaired capacity of the intestine to sufficiently absorb vital nutrients and electrolytes essential for growth and well-being in pediatric and adult populations. Although parenteral nutrition remains the mainstay therapeutic approach, the pursuit of a definitive and curative strategy, such as regenerative medicine, is imperative. Substantial advancements in the field of engineered intestinal tissues present a promising avenue for addressing intestinal failure; nevertheless, extensive research is still necessary for effective translation from experimental benchwork to clinical bedside applications.

American Association Of Plastic Surgeons Consensus On Breast Implant-Associated Anaplastic Large-Cell Lymphoma, Mark W Clemens, Terence M Myckatyn, Arianna Di Napoli, Andrew L Feldman, Elaine S Jaffe, Cara L Haymaker, Steven M Horwitz, Kelly K Hunt, Marshall E Kadin, Colleen M Mccarthy, Roberto N Miranda, H Miles Prince, Fabio Santanelli Di Pompeo, Sari D Holmes, Linda G Phillips

Faculty, Staff and Student Publications

BACKGROUND: In the absence of high-quality evidence, there is a need for guidelines and multidisciplinary consensus recommendations on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL). The purpose of this expert consensus conference was to evaluate the existing evidence regarding the diagnosis and management of BIA-ALCL caused by textured implants. This article aims to provide evidence-based recommendations regarding the management and prevention of BIA-ALCL.

METHODS: A comprehensive search was conducted in the MEDLINE, Cochrane Library, and Embase databases, and supplemented by manual searches of relevant English-language articles and "related articles" sections. Studies focusing on breast surgery and lymphoma associated with breast implants …

American Association Of Plastic Surgeons Consensus On Breast Implant-Associated Anaplastic Large-Cell Lymphoma, Mark W. Clemens, Terence M. Myckatyn, Arianna Di Napoli, Andrew L. Feldman, Elaine S. Jaffe, Cara L. Haymaker, Steven M. Horwitz, Kelly K. Hunt, Marshall E. Kadin, Colleen M Mccarthy, Roberto N. Miranda, H. Miles Prince, Fabio Santanelli Di Pompeo, Sari D. Holmes, Linda G. Phillips

2020-Current year OA Pubs

BACKGROUND: In the absence of high-quality evidence, there is a need for guidelines and multidisciplinary consensus recommendations on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL). The purpose of this expert consensus conference was to evaluate the existing evidence regarding the diagnosis and management of BIA-ALCL caused by textured implants. This article aims to provide evidence-based recommendations regarding the management and prevention of BIA-ALCL.

METHODS: A comprehensive search was conducted in the MEDLINE, Cochrane Library, and Embase databases, and supplemented by manual searches of relevant English-language articles and "related articles" sections. Studies focusing on breast surgery and lymphoma associated with breast implants …

Repeat Modules And N-Linked Glycans Define Structure And Antigenicity Of A Critical Enterotoxigenic E. Coli Adhesin, Zachary T. Berndsen, Marjahan Akhtar, Mahima Thapa, Tim J. Vickers, Aaron Schmitz, Pardeep Kumar, Nazia Khatoon, Alaullah Sheikh, Melissa Hamrick, Jackson S. Turner, Ali H. Ellebedy, James M. Fleckenstein, Et Al.

2020-Current year OA Pubs

Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of cases of infectious diarrhea annually, predominantly in children from low-middle income regions. Notably, in children, as well as volunteers challenged with ETEC, diarrheal severity is significantly increased in blood group A (bgA) individuals. EtpA, is a secreted glycoprotein adhesin that functions as a blood group A lectin to promote critical interactions between ETEC and blood group A glycans on intestinal epithelia for effective bacterial adhesion and toxin delivery. EtpA is highly immunogenic resulting in robust antibody responses following natural infection and experimental challenge of volunteers with ETEC. To understand how EtpA …

Rhesus Rotavirus Nsp1 Mediates Extra-Intestinal Infection And Is A Contributing Factor For Biliary Obstruction, Enkai Li, Ningguo Feng, Qiru Zeng, Liliana Sanchez-Tacuba, Takahiro Kawagishi, Grace Branham, Gaopeng Hou, Zemin Wang, Harry B. Greenberg, Siyuan Ding

2020-Current year OA Pubs

We previously demonstrated that in Ifnar1-/-Ifngr1-/- or Stat1-/- suckling mice lacking intact type I and type II interferon (IFN) signaling, rhesus rotavirus (RRV) infection causes a lethal disease with clinical manifestations similar to biliary atresia, including acholic stools, oily fur, growth retardation, and excess mortality. Elevated levels of viral RNA are detected in the bile ducts and liver of diseased pups together with severe inflammatory responses in these tissues. However, the viral determinants and the molecular mechanisms driving this process remain incompletely understood. Using an optimized rotavirus (RV) reverse genetics system, we generated a panel of recombinant RVs that encode …

Optimal Humanized Scg3-Neutralizing Antibodies For Anti-Angiogenic Therapy Of Diabetic Retinopathy, Chengchi Huang, Prabuddha Waduge, Avinash Kaur, Hong Tian, Christina Y Weng, John Timothy Stout, Iok-Hou Pang, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Secretogranin III (Scg3) is a diabetic retinopathy (DR)-restricted angiogenic factor identified in preclinical studies as a target for DR therapy. Previously, our group generated and characterized ML49.3, an anti-Scg3 monoclonal antibody (mAb) which we then converted into an EBP2 humanized antibody Fab fragment (hFab) with potential for clinical application. We also generated anti-Scg3 mT4 mAb and related EBP3 hFab. In this study, to identify the preferred hFab for DR therapy, we compared all four antibodies for binding, neutralizing and therapeutic activities in vitro and in vivo. Octet binding kinetics analyses revealed that ML49.3 mAb, EBP2 hFab, mT4 mAb and EBP3 …

Enterococcus Faecalis-Derived Adenine Enhances Enterohaemorrhagic Escherichia Coli Type 3 Secretion System-Dependent Virulence, Fernando H Martins, Thibaut Rosay, Anubama Rajan, Hannah E Carter, Tayah Turocy, Andres Mejia, Jason M Crawford, Anthony W Maresso, Vanessa Sperandio

Faculty, Staff and Students Publications

Interactions between microbiota and enteric pathogens can promote colonization resistance or enhance pathogenesis. The pathobiont Enterococcus faecalis increases enterohaemorrhagic E. coli (EHEC) virulence by upregulating Type 3 Secretion System (T3SS) expression, effector translocation, and attaching and effacing (AE) lesion formation on enterocytes, but the mechanisms underlying this remain unknown. Using co-infection of organoids, metabolomics, supplementation experiments and bacterial genetics, here we show that co-culture of EHEC with E. faecalis increases the xanthine-hypoxanthine pathway activity and adenine biosynthesis. Adenine or E. faecalis promoted T3SS gene expression, while transcriptomics showed upregulation of adeP expression, which encodes an adenine importer. Mechanistically, adenine relieved …

Targeting Calpain-2-Mediated Junctophilin-2 Cleavage Delays Heart Failure Progression Following Myocardial Infarction, Satadru K Lahiri, Jiao Lu, Yuriana Aguilar-Sanchez, Hui Li, Lucia M Moreira, Mohit M Hulsurkar, Arielys Mendoza, Mara R Turkieltaub Paredes, Jose Alberto Navarro-Garcia, Elda Munivez, Brooke Horist, Oliver M Moore, Gunnar Weninger, Sören Brandenburg, Christof Lenz, Stephan E Lehnart, Rana Sayeed, George Krasopoulos, Vivek Srivastava, Lilei Zhang, Jason M Karch, Svetlana Reilly, Xander H T Wehrens

Faculty, Staff and Students Publications

Coronary heart disease (CHD) is a prevalent cardiac disease that causes over 370,000 deaths annually in the USA. In CHD, occlusion of a coronary artery causes ischemia of the cardiac muscle, which results in myocardial infarction (MI). Junctophilin-2 (JPH2) is a membrane protein that ensures efficient calcium handling and proper excitation-contraction coupling. Studies have identified loss of JPH2 due to calpain-mediated proteolysis as a key pathogenic event in ischemia-induced heart failure (HF). Our findings show that calpain-2-mediated JPH2 cleavage yields increased levels of a C-terminal cleaved peptide (JPH2-CTP) in patients with ischemic cardiomyopathy and mice with experimental MI. We created …

Emergency Department Slit Lamp Interdisciplinary Training Via Longitudinal Assessment In Medical Practice, Samara Hamou, Shayan Ghiaee, Christine Chung, Maureen Lloyd, Kelly Khem, Xiao Zhang

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Eye emergencies make up nearly 3% of US emergency department (ED) visits. While emergency physicians (EP) should diagnose and treat these ophthalmologic emergencies, many trainees report limited ocular exposure and insufficient training throughout their residency to confidently conduct a thorough slit-lamp exam.

METHODS: We created an interdisciplinary, simulation-based mastery learning (SBML) curriculum to teach emergency attending physicians how to operate the slit lamp with multimodal learning methodology at a tertiary academic center. The EPs first demonstrate their initial slit-lamp competency with a 20-item checklist, and they then review the necessary curricular content to pass their independent readiness test before …

Diabetes Technology Meeting 2023, Tiffany Tian, Rachel E Aaron, Ashley Y Dunova, Johan H Jendle, David Kerr, Eda Cengiz, Andjela Drincic, John C Pickup, Kong Y Chen, Naomi Schwartz, Douglas B Muchmore, Halis K Akturk, Carol J Levy, Signe Schmidt, Riccardo Bellazzi, Alan H B Wu, Elias K Spanakis, Bijan Najafi, James Geoffrey Chase, Jane Jeffrie Seley, David C Klonoff

Center on Aging Staff Publications

Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 1 to November 4, 2023. Meeting topics included digital health; metrics of glycemia; the integration of glucose and insulin data into the electronic health record; technologies for insulin pumps, blood glucose monitors, and continuous glucose monitors; diabetes drugs and analytes; skin physiology; regulation of diabetes devices and drugs; and data science, artificial intelligence, and machine learning. A live demonstration of a personalized carbohydrate dispenser for people with diabetes was presented.

Molecular Detection Of Intestinal Parasites In A Rural Community Of Colombia: A One Health Approach To Explore Potential Environmental-Zoonotic Transmission, Sergio Castañeda, Claudia Patricia Acosta, Luis Reinel Vasquez-A, Luz H Patiño, Rojelio Mejía, Juan David Ramírez

Faculty, Staff and Students Publications

Aims: Protozoan and helminth parasitic infections pose significant public health challenges, especially in developing countries with rural populations marked by suboptimal hygiene practices and socio-economic constraints. The parasites are the etiological agents of these infections and have a notably elevated global prevalence. Therefore, this study focuses on estimating the frequency and transmission dynamics of several parasitic species, including Blastocystis, Giardia, Cryptosporidium spp., Entamoeba histolytica, Ascaris lumbricoides, Trichuris trichiura, Taenia spp. and hookworms, within a rural community in southwest Colombia with a particular emphasis on the One Health framework, considering environmental and zoonotic transmission potentials.

Methods and results: This study involved …

Psychosocial Outcomes Of Pain And Pain Management In Adults With Osteogenesis Imperfecta: A Qualitative Study, Whitney S Shepherd, Andrew D Wiese, Hannah E Cho, W Conor Rork, M Usman Baig, Kristin M Kostick, Dianne Nguyen, Erin M Carter, Members Of The Bbdc, Chaya N Murali, Marie-Eve Robinson, Sophie C Schneider, Brendan Lee, V Reid Sutton, Eric A Storch

Faculty, Staff and Students Publications

Objectives

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and fractures, short stature, dental abnormalities, hearing loss, scoliosis, and chronic pain. Despite a growing literature on the functional outcomes of OI, limited research has explicitly examined the psychosocial outcomes of pain within OI.

Methods

Adults with OI (N=15) were interviewed to understand pain-related experiences through a thematic analysis of semi-structured interview data. Research team members, genetic research experts, and OI clinicians developed an interview guide focused on topics related to pain and mental health challenges. Participants’ transcripts were coded by two independent coders; codes were then merged …

Exercise Referral Schemes In The Uk: Mapping Provision And Aims, Ben Jane, John Downey

School of Nursing and Midwifery

BackgroundExercise Referral Schemes (ERS) are designed so health professionals can refer certain patients to a supervised programme of physical activity. However, evaluations have questioned the effectiveness of these schemes/programmes. The aim of this study was to systematically review the provision of ERS in England and analyse related promotional material.MethodsContent analysis methods were used to analyse scheme websites and promotional material. A coding scheme was used to analyse the data, which included information on the programme’s aims, inclusion criteria, type of activities, accessibility and cost.ResultsThe study identified 625 sites offering ERS across 168 geographic areas. Findings highlighted a lack of clarity …

Loss Of Periostin Function Impairs Ligament Fibroblast Activity And Facilitates Ros-Mediated Cellular Senescence, Muhammad Farooq Rai, Xin Duan, Mingming Yan, Robert H Brophy, Lei Cai

2020-Current year OA Pubs

Anterior cruciate ligament (ACL) injuries pose a significant challenge due to their limited healing potential, often resulting in premature arthritis. The factors and mechanisms contributing to this inadequate healing process remain elusive. During the acute phase of injury, ACL tissues express elevated periostin levels that decline over time. The functional significance of periostin in ligament biology remains understudied. In this study, we investigated the functional and mechanistic implications of periostin deficiency in ACL biology, utilizing ligament fibroblasts derived from patients and a murine model of ACL rupture. Our investigations unveiled that periostin knockdown compromised fibroblast growth characteristics, hindered the egress …

Inhibition Of Ulk1/2 And Kras G12c Controls Tumor Growth In Preclinical Models Of Lung Cancer, Phaedra C Ghazi, Kayla T O'Toole, Sanjana Srinivas Boggaram, Michael T Scherzer, Mark R Silvis, Yun Zhang, Madhumita Bogdan, Bryan D Smith, Guillermina Lozano, Daniel L Flynn, Eric L Snyder, Conan G Kinsey, Martin Mcmahon

Faculty, Staff and Student Publications

Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRASG12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC). However, not all KRASG12C-driven NSCLCs respond to these inhibitors, and the emergence of drug resistance in those patients who do respond can be rapid and pleiotropic. Hence, based on a backbone of covalent inhibition of KRASG12C, efforts are underway to develop effective combination therapies. Here, we report that the inhibition of KRASG12C signaling increases autophagy in KRASG12C-expressing lung cancer …

Milvexian Vs Apixaban For Stroke Prevention In Atrial Fibrillation: The Librexia Atrial Fibrillation Trial Rationale And Design, Sneha S Jain, Kenneth W Mahaffey, Karen S Pieper, Wataru Shimizu, Tatjana Potpara, Christian T Ruff, Hooman Kamel, Basil S Lewis, Jan H Cornel, Peter R. Kowey, Jay Horrow, John Strony, Alexei N Plotnikov, Danshi Li, Stephen Weng, Julia Donahue, C Michael Gibson, P Gabriel Steg, Roxana Mehran, Jeffrey I Weitz, S Claiborne Johnston, Graeme J Hankey, Robert A Harrington, Carolyn S P Lam

Department of Medicine Faculty Papers

BACKGROUND: Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk.

METHODS: LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to …

Contrast Enhanced Ultrasound Of Liver Lesions In Patients Treated For Childhood Malignancies., Ayatullah Mostafa, Zachary Abramson, Mina Ghbrial, Som Biswas, Sherwin S. Chan, Himani Darji, Jessica Gartrell, Seth E. Karol, Yimei Li, Daniel A. Mulrooney, Tushar Patni, Tarek M. Zaghloul, M Beth Mccarville

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Patients treated for cancer have a higher incidence of focal liver lesions than the general population and there is often concern for a malignant etiology. This can result in patient, caregiver and physician anxiety and is managed by a "wait and watch" approach, or immediate additional imaging, or biopsy, depending on the degree of clinical concern. Because it is a low-cost, easily accessible, radiation and sedation free modality, we investigated the value of contrast enhanced ultrasound (CEUS) to accurately distinguish benign from malignant liver lesions in patients treated for childhood malignancies.

METHODS: We performed an IRB approved retrospective study …

Novel Framework Of Financial Hardship In Childhood Cancer: Incorporating Stakeholder Perspectives, Julie Ritter, Sara M Malone, Et Al.

2020-Current year OA Pubs

PURPOSE: Although financial hardship in childhood cancer contributes to poor outcomes, no standardized tool to assess its impact exists. Existing methods are heterogeneous and designed using high-income country (HIC), adult perspectives. This project aimed to construct a stakeholder-informed conceptual framework of financial hardship in childhood cancer with global relevancy.

METHODS: Group concept mapping, a participatory mixed-methods approach, was used. Participants were parents or caregivers of a child with cancer, childhood cancer survivors, and clinical or nonclinical support personnel, fluent in English, Spanish, or Portuguese. A representative panel established a comprehensive list of relevant items. Participants individually sorted these items into …