Medical Sciences Commons^™

Protocol For Establishing Genetically Engineered Murine Lung Organoids Mimicking Cell Plasticity And Regeneration, Bongjun Kim, Jae-Il Park

Faculty, Staff and Student Publications

Lung endothelial cells (LuECs) play crucial roles in lung regeneration and support lung organoids (LOs). However, detailed guidelines for LO culture using LuECs have not been reported yet. Here, we present an efficient protocol for generating and culturing murine LOs that mimic regeneration. We describe steps for the isolation of LuECs and lung epithelial cells, followed by LO culture. We also describe how to establish genetically engineered LOs using viral transduction. For complete details on the use and execution of this protocol, please refer to Kim et al.

Characterization And Clinical Implications Of P53 Dysfunction In Patients With Myelodysplastic Syndromes, Matteo Zampini, Elena Riva, Luca Lanino, Elisabetta Sauta, Rita Antunes Dos Reis, Rosa Maria Andres Ejarque, Giulia Maggioni, Alberto Termanini, Alessandra Merlotti, Alessia Campagna, Lorenzo Dall'olio, Austin Kulasekararaj, Michela Calvi, Clara Di Vito, Arturo Bonometti, Daoud Rahal, Giorgio Croci, Emanuela Boveri, Umberto Gianelli, Maurilio Ponzoni, Rossella Caselli, Serena Albertazzi, Gabriele Todisco, Marta Ubezio, Laura Crisafulli, Alessandro Frigo, Enrico Lugli, Ettore Mosca, Pamela Acha, Serena Ghisletti, Francesco Nicassio, Armando Santoro, Maria Diez-Campelo, Francesc Solé, Lionel Ades, Uwe Platzbecker, Valeria Santini, Pierre Fenaux, Torsten Haferlach, David Sallman, Guillermo Garcia-Manero, Domenico Mavilio, Daniel Remondini, Gastone Castellani, Saverio D'Amico, Amer M Zeidan, Rami Komrokji, Shahram Kordasti, Francesca Ficara, Matteo Giovanni Della Porta, Calr Consortium

Faculty, Staff and Student Publications

Purpose: Tumor Protein 53 (p53) expressed from gene TP53 is a seminal tumor suppressor. We aimed to characterize mutational and nonmutational mechanisms of p53 dysfunction in myelodysplastic syndromes (MDS) and to investigate their clinical effect.

Patients and methods: We analyzed a cohort of 6,204 patients with MDS and subsets of patients with available information on RNA sequencing of tumor cells (n = 109), high-dimensional phenotype of immune cells (n = 77), and multiomics analysis (RNA sequencing and proteomics) on single cells (n = 15). An independent validation was performed on 914 patients.

Results: Biallelic TP53 inactivation was a powerful driver …

Protocol For Assessing Mobilization Of Peritoneal B Cells To The Pre-Metastatic Omentum In An Orthotopic Mouse Model Of Ovarian Cancer, Wonjae Lee, Hironari Akasaka, Honami Naora

Faculty, Staff and Student Publications

The omentum is a visceral adipose tissue that undergoes dynamic immunological changes prior to and following metastasis. Here, we present a protocol for assessing the mobilization of peritoneal B cells to the pre-metastatic omentum in a mouse ovarian cancer model. We describe steps for isolation and adoptive transfer of peritoneal donor B cells and their detection in the omentum of recipient mice. This protocol could be utilized to study the mobilization of peritoneal B cells to the omentum in other pathological contexts. For complete details on the use and execution of this protocol, please refer to Lee et al.

Usp37 Counteracts Hltf To Protect Damaged Replication Forks And Promote Survival Of Brca1-Deficient Cells And Parp Inhibitor Resistance, Mengfan Tang, Siting Li, Ziqiang Zhu, Chao Wang, Shuai Ding, Huimin Zhang, Min Huang, Sarah Keast, Zhen Chen, Ling Yin, Litong Nie, Dan Su, Xu Feng, Junjie Chen

Faculty, Staff and Student Publications

Poly(ADP-ribose) polymerase inhibitors (PARPi) have greatly improved survival of cancer patients harboring BRCA1 mutations. However, therapy resistance develops via either restoration of homologous recombination or replication fork stabilization. Therapeutic targets to overcome PARPi resistance are critically needed. We identified the deubiquitinase USP37 as a key determinant of PARPi toxicity in BRCA1-deficient cells via whole-genome CRISPR screens. USP37 ablation enhanced PARPi sensitivity in BRCA1-deficient cells and also overcame PARPi resistance due to 53BP1 loss. USP37 interacts with and deubiquitinates replication protein A (RPA) at stalled replication forks to limit excessive RPA accumulation, progressive RPA exhaustion, and the conversion of RPA-coated single-stranded …

Risk Factors For Serious Bacterial Infections Among Young Infants With Hypothermia: Protocol For A Multicenter, Retrospective Case-Control Study, Sriram Ramgopal, Paul Aronson, Douglas Lorenz, Alexander Joseph Rogers, Andrea Tania Cruz

Faculty, Staff and Students Publications

Background: Hypothermia in young infants presenting to the emergency department (ED) may indicate a serious bacterial infection (SBI) such as a urinary tract infection, bacteremia, or bacterial meningitis. Improved understanding of the epidemiology of SBI in infants with hypothermia and the development of prediction models can help avoid unnecessary invasive procedures and antimicrobial exposure.

Objective: The aim of the study is to (1) describe the epidemiology of SBI and herpes simplex virus (HSV) among infants with hypothermia, (2) assess the role of biomarkers in predicting SBI, and (3) derive and internally validate a multivariable predictive model for SBI among infants …

Partial Least Squares Multimodal Analysis Of Brain Network Correlates Of Language Deficits In Aphasia, Sigfus Kristinsson, Dirk B. Den Ouden, Chris Rorden, Roger Newman-Norlund, Lisa Johnson, Janina Wilmskoetter, Ezequiel Gleichgerrcht, Argye E. Hillis, Gregory Hickok, Julius Fridriksson, Leonardo Bonilha

Communication Sciences and Disorders Faculty Articles and Research

Lesion-symptom mapping techniques are essential to determine brain regions critical for language functions. However, high collinearity in neuroimaging and behavioural data remains a challenge for distinguishing neural substrates supporting multiple language domains (shared variance) and those subserving specific language functions (unique variance). Here, we employed a novel approach to multimodal lesion-symptom mapping using multivariate partial least squares regression to delineate the latent structure of lesion-behavioural mapping in aphasia and decompose the shared and unique neural determinants of language impairments. A total of 86 participants with chronic (>12-month post-stroke) aphasia after left hemisphere strokes were examined. Language impairment was assessed …

Blood-Based Proteomic Profiling Identifies Osmr As A Novel Biomarker Of Aml Outcomes, Patrick K Reville, Bofei Wang, Jennifer Marvin-Peek, Bin Yuan, Yu-An Kuo, Araceli Garza, Jessica Root, Wei Qiao, Andrea Arruda, Ivo Veletic, Yiwei Liu, Nicholas J Short, Courtney D Dinardo, Tapan M Kadia, Naval G Daver, Philip L Lorenzi, Koji Sasaki, Steven Kornblau, Mark D Minden, Farhad Ravandi, Hagop M Kantarjian, Hussein A Abbas

Faculty, Staff and Student Publications

Inflammation is increasingly recognized as a critical factor in acute myeloid leukemia (AML) pathogenesis. We performed blood-based proteomic profiling of 251 inflammatory proteins in 543 patients with newly diagnosed AML. Using a machine learning model, we derived an 8-protein prognostic score termed the leukemia inflammatory risk score (LIRS). Individual proteins were evaluated in multivariable Cox models, and model performance was assessed by cumulative concordance index. Findings were validated in internal and external cohorts across 2 institutions. Blood-based LIRS significantly outperformed the European LeukemiaNet 2022 risk model and was independently prognostic of overall survival after accounting for known clinical and molecular …

Integrating Endocannabinoid Signaling, Cck Interneurons, And Hippocampal Circuit Dynamics In Behaving Animals, Shreya Malhotra, Florian Donneger, Jordan S Farrell, Barna Dudok, Attila Losonczy, Ivan Soltesz

Faculty, Staff and Students Publications

The brain's endocannabinoid signaling system modulates a diverse range of physiological phenomena and is also involved in various psychiatric and neurological disorders. The basic components of the molecular machinery underlying endocannabinoid-mediated synaptic signaling have been known for decades. However, limitations associated with the short-lived nature of endocannabinoid lipid signals had made it challenging to determine the spatiotemporal specificity and dynamics of endocannabinoid signaling in vivo. Here, we discuss how novel technologies have recently enabled unprecedented insights into endocannabinoid signaling taking place at specific synapses in behaving animals. In this review, we primarily focus on cannabinoid-sensitive inhibition in the hippocampus in …

Treatment Outcomes Of Successful M1 Versus M2 Thrombectomy For Low-Aspects Stroke Patients, Huanwen Chen, Marco Colasurdo, Hidetoshi Matsukawa, Conor Cunningham, Ilko Maier, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M Starke, Marios-Nikos Psychogios, Amir Shaban, Nitin Goyal, Shinichi Yoshimura, Hugo Cuellar, Brian Howard, Ali Alawieh, Ali Alaraj, Mohamad Ezzeldin, Daniele G Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Fazeel Siddiqui, Joshua Osbun, Roberto Crosa, Ramesh Grandhi, Charles Matouk, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Ergun Daglioglu, Richard Williamson, Pedro Navia, Shakeel Chowdhry, David J Altschul, Alejandro M Spiotta, Peter Kan

Faculty, Staff and Students Publications

Background

The effectiveness of endovascular thrombectomy (EVT) for low Alberta Stroke Program Early CT score (ASPECTS) stroke patients with occlusion of the second segment of the middle cerebral artery (M2) is unclear.

Methods

This was a multicenter retrospective study. Patients with M1 or M2 occlusions and low ASPECTS (< 6) who underwent successful EVT (modified treatment in cerebral ischemia score of 2b or higher) were included. Primary outcome was futile EVT reperfusion (defined as 90-day modified Rankin scale of 5 or 6). Other outcomes of interest include acceptable outcomes (modified Rankin scale of 3 or less) and intracranial hemorrhage (ICH), and all-cause 90-day mortality. Outcomes for M1 patients were compared to M2 patients with multivariable logistic regression models accounting for potential confounders.

Results

173 patients with M1 or M2 occlusions and low ASPECTS (< 6) who underwent successful EVT were identified. After multivariable adjustments, M2 patients had significantly higher odds of futile reperfusion (OR 5.48 [95%CI 1.91 to 15.7], p = 0.002), lower odds of acceptable outcomes (OR 0.33 [95%CI 0.12 to 0.89], p = 0.028), and higher odds of all-cause mortality (OR 4.90 [95%CI 1.65 to 14.5], p = 0.004). These findings suggest that EVT's efficacy for low-ASPECTS stroke patients may be diminished for patients with M2 occlusions. M2 occlusion was not significantly associated with ICH.

Conclusions

Among low-ASEPCTS stroke patients who underwent successful EVT, those with M2 occlusions had significantly higher odds of poor outcome compared to those with M1 occlusions.

Mucin4 (Muc4) Antibody Labeled With An Nir Dye Brightly Targets Pancreatic Cancer Liver Metastases And Peritoneal Carcinomatosis, Sunidhi Jaiswal, Siamak Amirfakhri, Javier Bravo, Keita Kobayashi, Abhijit Aithal, Sumbal Talib, Kavita Mallya, Maneesh Jain, Aaron M. Mohs, Robert M. Hoffman, Surinder K. Batra, Michael Bouvet

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND/OBJECTIVES: Pancreatic cancer is the fourth leading cause of deaths related to cancer. It is a highly aggressive malignancy and often metastasizes quickly to other parts of the body and organs. The most effective cure is surgical resection, which also is limited by tumor identification and clear tumor margin visualization. Previously, we used MUC4 antibodies labeled with IRDye800CW (anti-MUC4-IR800) to target primary human pancreatic cancer in orthotopic cell line mouse models.

METHODS: In the present study, we established a pancreatic cancer liver metastasis mouse model by implanting a tumor fragment in the liver and a peritoneal carcinomatosis mouse model by …

Oncolytic Adeno-Immunotherapy Improves Allogeneic Adoptive Her2car-Nk Function Against Pancreatic Ductal Adenocarcinoma, Greyson Biegert, Amanda Rosewell Shaw, Daisuke Morita, Caroline Porter, Ryu Matsumoto, Lisa Jatta, Noah Crooks, Mae Woods, Qizhi Cathy Yao, Robin Parihar, Masataka Suzuki

Faculty, Staff and Students Publications

Pancreatic ductal adenocarcinoma (PDAC) responds poorly to conventional treatments and immunotherapy. We previously developed a binary oncolytic/helper-dependent adenovirus system (CAdTrio) that facilitated oncolysis and expressed the immunomodulatory molecule interleukin-12 and a programmed death ligand 1 (PD-L1) blocking mini-antibody. Given that CAdTrio enhanced endogenous natural killer (NK) cell anti-tumor activity in humanized mice bearing PDAC tumors and that NK cells can be adoptively transferred to patients safely in the allogeneic setting, we hypothesized that a combination of CAdTrio and allogeneic NK cells expressing a HER2-specific chimeric antigen receptor (HER2.CAR-NK) would be an effective, entirely “off-the-shelf” treatment against …

Therapy, Safety, And Logistics Of Preoperative Vs Postoperative Stereotactic Radiation Therapy: A Preliminary Analysis Of A Randomized Clinical Trial, Debra Nana Yeboa, Jing Li, Ruitao Lin, Sujit S Prabhu, Thomas H Beckham, Kristina Woodhouse, Todd Allen Swanson, Jeffrey S Weinberg, Xuemei Wang, Xiaohan Chi, Chinenye Lynette Ejezie, Dima Suki, Chenyang Wang, Chibawanye Ene, Ian E Mccutcheon, Susan Mcgovern, Mary Frances Mcaleer, Martin Tom, Amol Ghia, Subha Perni, Wen Jiang, Brian De, Caroline Chung, Betty Y S Kim, Barbara J O'Brien, Jason T Huse, Jeffrey S Wefel, Laurence Court, Hussein Tawbi, Filip Janku, Nandita Guha-Thakurta, J Matthew Debnam, Jason Johnson, Ceylan Altintas Taslicay, Christopher Alvarez-Breckenridge, Shaan M Raza, Amy B Heimberger, Franco Demonte, Robert North, Tina M Briere, John F De Groot, Raymond Sawaya, David Grosshans, Frederick F Lang, Ganesh Rao, Sherise D Ferguson

Faculty, Staff and Student Publications

Importance: Preoperative stereotactic radiation therapy (SRT) vs postoperative SRT logistics and toxic effects provides clinically significant data on management outcomes.

Objective: To determine preoperative SRT logistics and safety profile compared with postoperative in patients with brain metastases.

Design, setting, and participants: This single-institution phase 3 randomized clinical trial included patients 18 years and older and undergoing a planned surgical resection. Patients were required to have an Eastern Cooperative Oncology Group Performance Status score of 2 or greater and be candidates for SRT within 30 days of surgical resection. Patients with radiosensitive histologies (eg, small cell lung cancer and lymphoma), brain …

The Multilayered Control Of Acetylation During Adenovirus-Based Immunotherapy Of Cancer, Akhila Parthasarathy, Maria Frost, Andrew G Gillard, Marta M Alonso, Candelaria Gomez-Manzano, Juan Fueyo

Faculty, Staff and Student Publications

Adenoviruses are highly immunogenic agents that have shown promise first as gene delivery vectors and later as oncolytic viruses. Currently, oncolytic adenoviruses are featured in over 30% of cancer virotherapy clinical trials. Due to their effective cellular uptake and hijack of cellular machinery, replication-competent adenoviruses are promising therapeutic agents for treating a wide range of tumors. Adenoviral influence on host cell acetylome regulation has regained attention, as these viruses redirect or suppress acetylation during replication, making them potentially desirable therapeutic agents for cancers driven by epigenetic modifications. In this review, we aim to cover the viral processes influencing the acetylome …

Microglial Phagocytosis In Epilepsy: Mechanisms And Impact, Abhijeet S Barath, Long-Jun Wu

The Brown Foundation: Institute of Molecular Medicine

Microglia are resident immune cells critical in maintaining brain homeostasis via their surveillance and phagocytosis function. Under disease contexts such as seizures and epilepsy, microglial phagocytic signalling is activated in response to both inflammatory and non-inflammatory cell death. This process involves a range of well-characterized 'find me' and 'eat me' signals, phagocytic receptors, and less well-characterized intracellular signalling pathways. In addition, epigenetic and transcriptional regulators orchestrate microglial responses to seizures, including the integration of phagocytic and inflammatory pathways. Interestingly, although inhibiting phagocytosis has been shown to improve neuronal survival and cognitive performance after seizures, it paradoxically increases the risk of …

Perceived Neighborhood Crime And Gun Carrying Behavior: Examining The Role Of A History Of Traumatic Brain Injury, Eric J Connolly, Anne C Wingert, Dennis E Reidy, Jarrad D Hodge, Jeff R Temple

Faculty, Staff and Student Publications

Background: Individuals living in high crime neighborhoods are more likely to carry a firearm. Members of these communities are also more likely to experience a traumatic brain injury (TBI) in their lifetime, which is a common correlate of hypervigilance and aggression. The current study evaluates the independent and interactive effects of TBI on perceived levels of neighborhood crime and gun carrying.

Methods: Data from 2015 to 2017 from a longitudinal ethnically diverse sample of adolescents and young adults are analyzed (Ns = 600-734). Multivariate logistic regression models are estimated to evaluate associations between perceived levels of neighborhood crime, TBI, gun …

X-Linked Hypophosphatemia Management In Children: An International Working Group Clinical Practice Guideline., Dalal S. Ali, Thomas O. Carpenter, Erik A. Imel, Leanne M. Ward, Natasha M. Appelman-Dijkstra, Catherine Chaussain, Suzanne M. Jan De Beur, Pablo Florenzano, Hajar Abu Alrob, Rana Aldabagh, R Todd Alexander, Farah Alsarraf, Signe Sparre Beck-Nielsen, Martin Biosse-Duplan, Rachel K. Crowley, Karel Dandurand, Guido Filler, Lisa Friedlander, Seiji Fukumoto, Claudia Gagnon, Paul Goodyer, Corinna Grasemann, Chelsey Grimbly, Salma Hussein, Muhammad K. Javaid, Sarah Khan, Aneal Khan, Anna Lehman, Willem F. Lems, E Michael Lewiecki, Ciara Mcdonnell, Reza D. Mirza, Emmett Morgante, Archibald Morrison, Anthony A. Portale, Christina Rao, Yumie Rhee, Eric T. Rush, Heide Siggelkow, Sotirios Tetradis, Laura Tosi, Gordon Guyatt, Maria Luisa Brandi, Aliya A. Khan

Manuscripts, Articles, Book Chapters and Other Papers

CONTEXT: An International Working Group (IWG) developed new guidelines on the diagnosis, evaluation, management, and monitoring of X-linked hypophosphatemia (XLH) in children. Over the past 5 years, important advances have occurred in our understanding of the presentation, complications, and treatment of XLH.

METHODS: A group of 50 international experts in XLH from Canada, the United States, Europe, Asia, and South America, along with methodology experts and a patient partner, held 18 teleconference meetings in 2023-2024. These meetings addressed key issues regarding diagnosing, evaluating, managing, and monitoring XLH in children. Two systematic reviews were conducted to examine the impact of burosumab …

Clinical And Radiological Features Of Atypical Adrenal Masses-A Multicenter Retrospective Study, Vania Balderrama-Brondani, Ruaa Al-Ward, Katja Kiseljak-Vassiliades, Lauren Fishbein, Danielle Dawes, Oksana Hamidi, Reza Pishdad, Juan Pablo Perdomo Rodriguez, Mohamad Anas Sukkari, Joseph R Grajo, Hans Kumar Ghayee, Sara Bedrose, Roland L Bassett, Amir H Hamrahian, Mouhammed Amir Habra

Faculty, Staff and Students Publications

Context: The natural history and malignant potential of cases classified as atypical adrenal masses (AAMs) are unknown.

Objective: To describe the radiological characteristics and clinical outcomes of AAMs.

Design and participants: A multicenter retrospective study. Patients ≥18 years old with AAMs [diameter of 10-39 mm on first imaging study and pre-contrast attenuation of >10 Hounsfield units (HU) on computed tomography] were studied. We excluded adrenal metastasis, pheochromocytoma, sarcoma, lymphoma, infiltrative lesions, and adrenal hemorrhage, as well as patients with genetic predisposition to adrenal neoplasms. Data are presented as percentages and median values with interquartile ranges (IQRs).

Results: We included 217 …

Btp2 Restricts Tulane Virus And Human Norovirus Replication Independent Of Store-Operated Calcium Entry, Francesca J Scribano, J Thomas Gebert, Kristen A Engevik, Nicole M Hayes, Jorge Villanueva, Son Pham, Soni Kaundal, Janam J Dave, B V Venkataram Prasad, Mary K Estes, Sasirekha Ramani, Joseph M Hyser

Faculty, Staff and Students Publications

Human norovirus is the leading cause of viral gastroenteritis across all age groups. While there is a need for human norovirus antivirals, therapeutic development has been hindered by a lack of cell culture systems and animal models of infection. Surrogate viruses, such as Tulane virus (TV), have provided tractable systems to screen potential antiviral compounds. Our previous work demonstrated that TV encodes a viral ion channel, which dysregulates cytosolic calcium signaling. We set out to investigate whether host pathways triggered by viral ion channel activity, including store-operated calcium entry (SOCE), play a role in virus replication. Using pharmacologic inhibitors and …

Proteogenomic Analysis Of The Calgb 40601 (Alliance) Her2+ Breast Cancer Neoadjuvant Trial Reveals Resistance Biomarkers, Eric J Jaehnig, Aranzazu Fernandez-Martinez, Tanmayi D Vashist, Matthew V Holt, Laterrica Williams, Jonathan T Lei, Chang In Moon, Beom-Jun Kim, Yongchao Dou, Haoquan Zhao, Viktoriya Korchina, Richard A Gibbs, Donna Marie Muzny, Harshavardhan Doddapaneni, Charles M Perou, Lisa A Carey, Ana I Robles, Terry Hyslop, Yujia Wen, Linda Mccart, Azra Krek, Francesca Petralia, George Miles, Shyam M Kavuri, Michael A Gillette, D R Mani, Steven A Carr, Bing Zhang, Matthew J Ellis, Shankha Satpathy, Meenakshi Anurag

Faculty, Staff and Students Publications

Proteogenomic analysis is applied to samples from the CALGB 40601 (Alliance) randomized neoadjuvant trial of trastuzumab, lapatinib, or the combination to identify biomarkers associated with pathological response status. Absence of ERBB2 gene amplification and human epidermal growth factor receptor 2 (HER2) protein overexpression by proteogenomics is associated with non-pathological compete response (pCR) (p < 0.05), highlighting potential false positives from standard diagnostics. Pathway analysis in proteogenomics-confirmed HER2+ samples identifies elevated epithelial-mesenchymal transition (EMT) and WNT-β-catenin signaling in non-pCR cases before treatment. Twenty-four pCR-associated proteins reproduce in a second proteomic dataset, and four (GPRC5A, TPBG, SP140L, and NEU1) are significant in a third. A meta-analysis of ten diverse neoadjuvant anti-HER2 treatment regimens from four independent studies confirms that non-pCR cases express higher levels of mRNA for G protein-coupled receptor class C group 5 member A (GPRC5A, p = 0.0002) and trophoblast glycoprotein (TPBG, p = 0.00008). Thus, proteogenomic analysis identifies negative biomarkers for pCR and alternative plasma membrane targets for treatment-resistant HER2+ breast cancer.

The Maturity-Onset Diabetes Of The Young (Mody) Calculator Overestimates Mody Probability In Hispanic Youth, Guido Alarcon, Anh Nguyen, Angus Jones, Beverley Shields, Maria J Redondo, Mustafa Tosur

Children’s Nutrition Research Center Staff Publications

Context: The applicability of the maturity-onset diabetes of the young (MODY) risk calculator to non-White European populations remains unknown.

Objective: We aimed to test its real-world application in Hispanic youth.

Methods: We conducted a retrospective chart review of Hispanic youth (< 23 years) with diabetes (n = 2033) in a large pediatric tertiary care center in the United States. We calculated MODY probability for all subjects, splitting them into 2 cohorts based on the original model: individuals who were started on insulin within 6 months of diabetes diagnosis (Cohort 1) and those who were not (Cohort 2).

Results: Cohort 1 consisted of 1566 individuals (median age [25p, 75p]: 16 [13, 19] years, 49% female), while Cohort 2 comprised 467 youth (median age [25p, 75p]: 17 [15, 20] years, 62% female). The mean MODY probability was 5.9% and 61.9% in Cohort 1 and Cohort 2, respectively. The mean probability for both cohorts combined was 18.8%, suggesting an …

Dosimetric Advantage Of Scanning Beam Proton Therapy In Gynecologic Patients Receiving Adjuvant Radiotherapy, Rachel B Ger, Jarrod M Lentz, Joshua S Niedzielski, Sujay A Vora, Martin Bues, Danairis Hernandez Morales, Justin D Anderson, Christopher J Kutyreff, Christie A Schulz, Pedro R Lara, Ana K Ridgway, Pamela R Lemish, Justin D Gagneur, Aman Anand

Faculty, Staff and Student Publications

Background/Objectives: Adjuvant radiation for gynecologic malignancies often exposes organs at risk (OARs), such as the bone marrow, bowel, rectum, and bladder, to radiation, leading to toxicities that impact treatment tolerance and patient quality of life. Scanning proton beam therapy, particularly with Individual Field Simultaneous Optimization (IFSO), may offer dosimetric and biological advantages over volumetric modulated arc therapy (VMAT). This study evaluates the clinical impact of IFSO-based proton planning in post-operative gynecologic cancer patients.

Materials and Methods: Fourteen patients receiving adjuvant proton therapy to 45 Gy in 25 fractions were retrospectively analyzed. Comparison VMAT plans were generated on the same datasets. …

Aso Visual Abstract: Characterization Of The Germline Pathogenic Mutational Landscape And Oncologic Outcomes Among 877 Patients With Invasive Lobular Carcinoma, Victoria D Huynh, Jason Mouabbi, Henry M Kuerer, Kerollos Nashat Wanis, Hiam M Abdel-Salam, Angelica M Gutierrez, Helen M Johnson, Anthony Lucci, Kelly K Hunt, Banu K Arun

Faculty, Staff and Student Publications

No abstract provided.

Environmental Screening For Multidrug Resistant (Mdr) Organisms In The Surgical Ward Of An Irish Tertiary Referral Hospital., Sinead A. Fahy, Sinéad Fahy

ORBioM (Open Research BioSciences Meeting)

The aim of the current study was to determine the prevalence of Multidrug Resistant Organisms (MDRO) colonisation on a surgical ward of an acute tertiary hospital. MDRO determination was conducted on a patient-occupied surgical ward over a 6-month period. The screen included sink, and shower drains in bathrooms and sinks of multi-bedded and single-occupied rooms. Swabs were cultured on chromogenic agar to enable detection of methicillin resistant Staphylococcus aureus (MRSA), Carbapenemase producing enterobacterales (CPE), Vancomycin Resistant Enterococci (VRE) and Extended spectrum beta-lactamase (ESBL). Suspect resistant organisms were confirmed using NG-Carba 5 (NG Biotech, Guipry, France) lateral flow tests, Vitek 2.0 …

An Evaluation Of The Monospot Test To Diagnose Epstein-Barr Virus Associated Infectious Mononucleosis (Ebv-Im), Patrick Naughton

ORBioM (Open Research BioSciences Meeting)

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Abstract

Aim

To calculate the performance characteristics of the Clearview^® IM II Monospot [heterophile antibody (HA) test] to determine Infectious Mononucleosis associated with Epstein-Barr Virus (EBV-IM) in clinically suspect patients.

Methods

The laboratory results of 420 patients tested for HAs over a two-year period (2018-2019) in a single testing centre in Ireland were analysed. A novel multivariant test (reference) model was designed to determine true positive and negative EBV-IM cases. A cohort of 50 Monospot results were compared against this reference model and the test’s performance characteristics determined.

Results

The Monospot test proved reasonably specific but insensitive …

Updates In Cryopreservation And Assisted Reproductive Techniques, Maha Abd Aljabbar Al-Sammak

BioMed Visions Journal

Cryopreservation is a crucial part of assisted reproductive technologies (ART) that has developed to maintain gametes and embryos viable for long periods of time. Recent technological developments, such as vitrification and innovative cryoprotectant that have significantly raised pregnancy success rates and enhanced embryo viability are highlighted in this review. The integration of state-of-the-art technology like single-cell sequencing is explored, and persistent issues with genetic stability and cryoinjury are addressed. The necessity for strong international regulations is emphasized in the discussion of ethical issues, especially those pertaining to the long-term storage and use of embryos. These developments are influencing the direction …

Comparative Study Between Multiple Insulin Doses Regimen Versus Twice Daily Regimen In Children And Teenagers With Type One Diabetes In Mosul City, Raghad T. Aziz, Nourhan T. Younis, Sarmad O. Rashid, Zakaria A Kassim

BioMed Visions Journal

Objectives: To evaluate the glycemic control and to identify the possible side effects of multiple insulin regimen versus twice daily regimen among diabetic patients whom visited the endocrine unit at Al Khansa’a Teaching Hospital in Mosul from the 1^st of January 2023 to the end of December 2023.

Methods: This is a cohort descriptive study. Patients case sheets were reviewed to acquire the mandatory information. The questionnaire was composed of two sections, first section included demographic information while the second covered specific diabetes Mellitus information.

Results: Sixty-nine children with type 1 diabetes were included in the study, with …

In Silico Screening For Computational Exploration Of Interactions, Synthesis, And Comparative Evaluation Of Novel Furan-2-Quinolone Derivatives As Potent Anticoagulants, Karm A. Khalaf, Noor A. Majeed, Adnan O. Omar

BioMed Visions Journal

There is an urgent need for the design and development of new and safer drugs for the treatment of (Blood coagulation). New derivatives of furan-2-qoinoline as anti-coagulation drug bearing furan, quinolone, were synthesized with the aim of developing new drug inhibitors (Factor Xa enzyme) respectively. In our study, synthesis of the new organic compounds derived from Furo-2-quinolone substituted by treated with ammonia derivatives like hydrazine, give K6, and (1-Amino-4,6-dimethyl furo[3,2-g] quinoline-2-one) K6 then react with Formaldehyde to form K6a. And evaluated their effects on coagulation in the docking (MCULE). then compared this compound, with the Rivaroxaban. compound give the result …

Public Acceptance, Attitude And Perception Toward Covid-19 Vaccination In Mosul City; Iraq, Nadia Hazem Saied

BioMed Visions Journal

Background: No doubt the recent coronavirus disease (COVID-19) pandemic represents the most serious health and life threats globally. Vaccination against the disease is considered the cornerstone for controlling the disease.

Aim of the study is to explore public attitudes, perception toward vaccination against COVID-19 infection.

Material and methods: A cross-sectional study was conducted by using a modified questionnaire form which was translated into Arabic language and transformed into a Google form. The form was disseminated to the population online using different platforms in Mosul City over a period of one month during November 2021 and the participants were volunteered for …

Top Ten Types Of Childhood Cancer In Nineveh Governorate 2018–2022: A Time Series Analysis, Marab Younis Abdullah Al-Fathy, Ahmed Asaad Hussein, Hiba Farooq Mohamed Ameen, Maan Younis Al-Fathi

BioMed Visions Journal

Background: Childhood cancer incidence and deaths reflects the low health status, which can be prevented by setting upstrategies with help of different sectors in community.

Aim: To describe the childhood cancer in Nineveh governorate during 2018–2022.

Methods: A Biometry study used to review 646 a cancer registration form for five years 2018–2022, using Can-Rej 5 inquiryforms adopted by Ministry of Health measuring [sex ratio, sex and cause specific death rate, the incidence rate, the case fatalityrate, the proportion mortality rate and trend of (occurrences and death)].

Results: The total number of participants was 646, the commonest childhood cancer was among …

The Relation Between Carpal Tunnel Syndrome And Ulnar Nerve Entrapment: An Electrophysiological Study, Mohammed Issa Suleiman

BioMed Visions Journal

Entrapment of the median nerve; carpal tunnel syndrome (CTS), is a common neuropathy that result from compression, ischemia or repetitive movement of the wrist. Ulnar nerve entrapment (UNE) frequency come after the median nerve syndrome, it occurs at the wrist and at the elbow. The neurological finding of median and ulnar nerves compression are presented as a sensory or motor or both.

Aim of the study: To investigate the frequency of carpal tunnel syndrome (CTS) and ulnar nerve entrapment (UNE).

Material and method: Fifty patients were included in this study suffering from CTS. The patients with the CTS diagnosis through; …