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Microglial Phagocytosis In Epilepsy: Mechanisms And Impact, Abhijeet S Barath, Long-Jun Wu Jun 2025

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 …


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 Jun 2025

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 …


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 Jun 2025

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 …


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 Jun 2025

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 …


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 Jun 2025

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 …


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 Jun 2025

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.


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 Jun 2025

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 …


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 Jun 2025

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.


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 Jun 2025

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 …


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 Jun 2025

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 Jun 2025

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. …


Atad3 Is Essential For Mitochondrial Permeability Transition Pore Opening And Cardiac Ischemia Reperfusion Injury, Dexter Robichaux, Sual J Lopez, Arielys Mendoza, Daniel Ramirez, Suh-Chin J Lin, Jeffery D Molkentin, Pablo M Peixoto, Jason Karch Jun 2025

Atad3 Is Essential For Mitochondrial Permeability Transition Pore Opening And Cardiac Ischemia Reperfusion Injury, Dexter Robichaux, Sual J Lopez, Arielys Mendoza, Daniel Ramirez, Suh-Chin J Lin, Jeffery D Molkentin, Pablo M Peixoto, Jason Karch

Faculty, Staff and Students Publications

The molecular identity of the mitochondrial permeability transition pore (mPTP) has remained elusive since the discovery of its existence over 75 years ago. Despite the numerous candidate proteins proposed, none have withstood genetic ablation, leaving them relegated to auxiliary regulatory roles. To date, no essential mPTP component has been identified. Here, we establish ATAD3 as the first essential component of the mPTP. Genetic deletion of Atad3 in cardiomyocytes and hepatocytes renders heart and liver mitochondria incapable of undergoing Ca 2+ -induced mPTP-dependent swelling. Moreover, these mitochondria exhibit the highest Ca 2+ retention capacity ever reported following genetic perturbation of the …


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 Jun 2025

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 …


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 Jun 2025

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 …


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 Jun 2025

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.


Environmental Screening For Multidrug Resistant (Mdr) Organisms In The Surgical Ward Of An Irish Tertiary Referral Hospital., Sinead A. Fahy, Sinéad Fahy Jun 2025

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 Jun 2025

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 Jun 2025

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 Jun 2025

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 1st 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 Jun 2025

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 Jun 2025

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 Jun 2025

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 Jun 2025

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; …


Tomoxifen Mono-Therapy For Breast Cancer In Elderly Women, Shahbaa A Al-Bayati, Taha H Al-Siagh, Faris A Ahmed Jun 2025

Tomoxifen Mono-Therapy For Breast Cancer In Elderly Women, Shahbaa A Al-Bayati, Taha H Al-Siagh, Faris A Ahmed

BioMed Visions Journal

Background: Tamoxifen is an estrogen antagonist used as neo-adjuvant drug for breast cancer treatment in women.

Objective: To evaluate tamoxifen monotherapy on breast cancer for elderly women with estrogen positive, progesterone positive, and Her2/neu negative.

Materials and methods: Seventeen breast cancer women were examined. The age range of the patients was between 73 and 87 years (mean ± SD: 79.2 ± 3.8 years). The patients were examined and diagnosed by a surgeon, and histopathologic examination. The patients included in the study were estrogen positive, progesterone positive, and Her2/neu negative. The patients were treated with tamoxifen monotherapy 20 mg/day orally during …


Do Perceived Social Support And Positive Religious Coping Moderate Any Relationship Between Post-Intensive Care Syndrome–Family Symptoms And Quality Of Life In Informal Caregivers Of Intensive Care Unit Survivors?, Carol R. Hirschkorn Jun 2025

Do Perceived Social Support And Positive Religious Coping Moderate Any Relationship Between Post-Intensive Care Syndrome–Family Symptoms And Quality Of Life In Informal Caregivers Of Intensive Care Unit Survivors?, Carol R. Hirschkorn

Doctoral Dissertations and Projects

Family members and close friends often act as informal caregivers (CGs) for survivors of critical illness, assisting with activities of daily living, ongoing care needs, and adjustment to life after critical illness. These CGs simultaneously cope with their own mental, physical, and social sequelae, including significant changes (to roles and responsibilities) in everyday life. Qualitative researchers have examined this constellation of CG symptoms, which constitute post-intensive care syndrome–family (PICS-F), to understand the experiences, needs, and coping of CGs of intensive care unit (ICU) survivors. None have looked at the impact of religious coping and perceived social support on PICS-F and …


Intouch Week Of June 16, 2025, New York Medical College Jun 2025

Beyond The Genome: The Racialized Exposome, Flourishing, And Stress Biology In African Americans, A Non-Exhaustive Review, Enye Washington Jun 2025

Beyond The Genome: The Racialized Exposome, Flourishing, And Stress Biology In African Americans, A Non-Exhaustive Review, Enye Washington

University Honors Theses

Racial health disparities remain an enduring challenge in the United States, disproportionately impacting African American communities through higher rates of chronic disease and premature mortality. This non-exhaustive literature explores how the racialized exposome - a term denoting the totality of social, environmental, and structural stressors rooted in systemic racism - biologically embeds itself via stress-responsive pathways. Specifically, it examines the interaction between racial stress, flourishing, and key biological markers, including allostatic load and telomere length, considering the gut-brain axis. The review highlights robust evidence that chronic exposure to racial discrimination and structural adversity contributes to multisystem dysregulation and accelerated cellular …


Performance Of A Novel Stool Quantitative Polymerase Chain Reaction Assay For Pediatric Tuberculosis Detection In Sub-Saharan Africa, Anca Vasiliu, Lucia Carratala-Castro, Abigail Seeger, Joanna Ehrlich, Babongile Nkala, Tara Ness, Miguel Mario Cumbe, Durbbin Mulengwa, Shilzia Munguambe, Bariki Mtafya, Edson Mambuque, Nosisa Shiba, Sozinho Acacio, Lilian Komba, Clement Gascua Adu-Gyamfi, H Lester Kirchner, Christoph Lange, Andrew R Dinardo, Alberto L Garcia-Basteiro, Anna Maria Mandalakas, Alexander Kay Jun 2025

Performance Of A Novel Stool Quantitative Polymerase Chain Reaction Assay For Pediatric Tuberculosis Detection In Sub-Saharan Africa, Anca Vasiliu, Lucia Carratala-Castro, Abigail Seeger, Joanna Ehrlich, Babongile Nkala, Tara Ness, Miguel Mario Cumbe, Durbbin Mulengwa, Shilzia Munguambe, Bariki Mtafya, Edson Mambuque, Nosisa Shiba, Sozinho Acacio, Lilian Komba, Clement Gascua Adu-Gyamfi, H Lester Kirchner, Christoph Lange, Andrew R Dinardo, Alberto L Garcia-Basteiro, Anna Maria Mandalakas, Alexander Kay

Faculty, Staff and Students Publications

Background: Children have paucibacillary tuberculosis and cannot provide expectorated sputum. Invasive specimen collection, by gastric aspiration or sputum induction, has a low diagnostic yield. In this study, we aimed to evaluate the diagnostic performance and additive yield of a novel stool-based assay in children diagnosed with tuberculosis in sub-Saharan Africa.

Methods: We conducted a prospective case-control study from October 2020 to June 2023 in Eswatini, Mozambique, and Tanzania. Children under 15 years newly diagnosed with tuberculosis completed clinical examination, chest radiography, culture, sputum Xpert Ultra, stool Xpert Ultra, and stool-based quantitative polymerase chain reaction (stool qPCR) assessment. Stool qPCR sensitivity …


Comparative Impact Of Thiazides Vs. Dihydropyridines On Heart Failure Risk In Hypertensive Patients: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Safaa M. Alsanosi, Yosra Z. Alhindi Jun 2025

Comparative Impact Of Thiazides Vs. Dihydropyridines On Heart Failure Risk In Hypertensive Patients: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Safaa M. Alsanosi, Yosra Z. Alhindi

Saudi Toxicology Journal

Background: Uncontrolled hypertension (HTN) is a progressive condition that significantly elevates the risk of heart failure (HF). The selection of antihypertensive agents plays a critical role in modulating HF risk. Thiazide diuretics and dihydropyridine calcium channel blockers (DHPs) are frequently utilized in clinical practice, yet their comparative long-term cardiovascular outcomes, particularly regarding HF incidence, remain underexplored. Methods: A systematic literature review was undertaken, drawing four key databases—MEDLINE, EMBASE, Web of Science, and Cochrane—covering the period from 1994 to October 2024. The scope was limited to randomized controlled trials (RCTs) evaluating thiazides or DHPs, with a minimum of 100 participants diagnosed …


The Tumor Suppressor Hnrnpk Induces P53-Dependent Nucleolar Stress To Drive Ribosomopathies, Pedro Aguilar-Garrido, María Velasco-Estévez, Miguel Ángel Navarro-Aguadero, Álvaro Otero-Sobrino, Marta Ibáñez-Navarro, Miguel Ángel Marugal, María Hernández-Sánchez, Prerna Malaney, Ashley Rodriguez, Oscar Benitez, Xiaroui Zhang, Marisa Jl Aitken, Alejandra Ortiz-Ruiz, Diego Megías, Manuel Pérez, Gadea Mata, Jesús Gomez, Miguel Lafarga, Orlando Domínguez, Osvaldo Graña-Castro, Eduardo Caleiras, Pilar Ximénez-Embun, Marta Isasa, Paloma Jimena De Andres, Sandra Rodríguez-Perales, Raúl Torres-Ruiz, Enrique Revilla, Rosa María García-Martín, Daniel Azorín, Josune Zubicaray, Julián Sevilla, Oleksandra Sirozh, Vanesa Lafarga, Joaquín Martínez-López, Sean M Post, Miguel Gallardo Jun 2025

The Tumor Suppressor Hnrnpk Induces P53-Dependent Nucleolar Stress To Drive Ribosomopathies, Pedro Aguilar-Garrido, María Velasco-Estévez, Miguel Ángel Navarro-Aguadero, Álvaro Otero-Sobrino, Marta Ibáñez-Navarro, Miguel Ángel Marugal, María Hernández-Sánchez, Prerna Malaney, Ashley Rodriguez, Oscar Benitez, Xiaroui Zhang, Marisa Jl Aitken, Alejandra Ortiz-Ruiz, Diego Megías, Manuel Pérez, Gadea Mata, Jesús Gomez, Miguel Lafarga, Orlando Domínguez, Osvaldo Graña-Castro, Eduardo Caleiras, Pilar Ximénez-Embun, Marta Isasa, Paloma Jimena De Andres, Sandra Rodríguez-Perales, Raúl Torres-Ruiz, Enrique Revilla, Rosa María García-Martín, Daniel Azorín, Josune Zubicaray, Julián Sevilla, Oleksandra Sirozh, Vanesa Lafarga, Joaquín Martínez-López, Sean M Post, Miguel Gallardo

Faculty, Staff and Student Publications

The nucleolus is a membraneless organelle and an excellent stress sensor. Any changes in its architecture or composition lead to nucleolar stress, resulting in cell cycle arrest and interruption of ribosomal activity, critical factors in aging and cancer. In this study, we identified and described the pivotal role of the RNA-binding protein HNRNPK in ribosome and nucleolar dynamics. We developed an in vitro model of endogenous HNRNPK overexpression and an in vivo mouse model of ubiquitous HNRNPK overexpression. These models showed disruptions in translation as the HNRNPK overexpression caused alterations in the nucleolar structure, resulting in p53-dependent nucleolar stress, cell …