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A Putative Camp-Binding Protein In Trypanosoma Brucei Cooperates With Flam3 To Promote Flagellar Connection And Cell Morphogenesis Nov 2024

A Putative Camp-Binding Protein In Trypanosoma Brucei Cooperates With Flam3 To Promote Flagellar Connection And Cell Morphogenesis

Faculty, Staff and Student Publications

Trypanosoma brucei is a flagellated parasitic protozoan, and within the insect vector the parasite transitions from the trypomastigote form to the epimastigote form by repositioning its mitochondrial genome and relocating the flagellum. The mechanisms underlying such morphology changes are still poorly understood, but several flagellum-localized proteins are involved in this process by modulating the flagellum attachment zone (FAZ) that adheres the flagellum to the cell membrane. We report here a putative cAMP-binding protein named cAMP-BP1, which promotes flagellar connection and morphology transition. cAMP-BP1 contains two cyclic nucleotide-binding domains and five calcium-binding C2 domains and localizes to the flagella connector and …


White Matter And Latency Of Visual Evoked Potentials During Maturation: A Miniature Pig Model Of Adolescent Development, P Leon Brown, Els Fieremans, Ali Abdollahzadeh, Korrapati V Sathyasaikumar, Sarah M Clark, Robert Schwarcz, Paul D Shepard, Greg I Elmer Nov 2024

White Matter And Latency Of Visual Evoked Potentials During Maturation: A Miniature Pig Model Of Adolescent Development, P Leon Brown, Els Fieremans, Ali Abdollahzadeh, Korrapati V Sathyasaikumar, Sarah M Clark, Robert Schwarcz, Paul D Shepard, Greg I Elmer

Faculty, Staff and Student Publications

Background: Continuous myelination of cerebral white matter (WM) during adolescence overlaps with the formation of higher cognitive skills and the onset of many neuropsychiatric disorders. We developed a miniature-pig model of adolescent brain development for neuroimaging and neurophysiological assessment during this critical period. Minipigs have gyroencephalic brains with a large cerebral WM compartment and a well-defined adolescence period.

Methods: Eight Sinclair™ minipigs (Sus scrofa domestica) were evaluated four times during weeks 14-28 (40, 28 and 28 days apart) of adolescence using monocular visual stimulation (1 Hz)-evoked potentials and diffusion MRI (dMRI) of WM. The latency for the pre-positive 30 ms …


Analyzing Llama 3-Based Approach For Axiom Translation From Ontologies, Muhammad Amith Nov 2024

Analyzing Llama 3-Based Approach For Axiom Translation From Ontologies, Muhammad Amith

Faculty, Staff and Student Publications

Ontology development involves a top-down approach where ontology engineers and domain experts collaboratively define and evaluate ontological elements and axioms. Translating ontology axioms into natural language can significantly aid in ontology evaluation by making the content more understandable to subject matter experts who may lack a background in knowledge engineering. In this preliminary study, we investigate the potential of large language models (LLMs) in axiom translation from ontologies to facilitate ontology evaluation. We utilize Llama 3 to translate 1,192 ontology axioms across 19 distinct axiom types from five published ontologies. Results show that 163 (13.67%) of the Llama 3 translation …


Solid Tumour-Induced Systemic Immunosuppression Involves Dichotomous Myeloid-B Cell Interactions, Angela Alexander, Ling Wu, Zhan Xu, Liqun Yu, Yang Gao, Fengshuo Liu, Hilda L Chan, Che-Hsing Li, Yunfeng Ding, Weijie Zhang, David G Edwards, Nan Chen, Azadeh Nasrazadani, Naoto T Ueno, Bora Lim, Xiang H-F Zhang Nov 2024

Solid Tumour-Induced Systemic Immunosuppression Involves Dichotomous Myeloid-B Cell Interactions, Angela Alexander, Ling Wu, Zhan Xu, Liqun Yu, Yang Gao, Fengshuo Liu, Hilda L Chan, Che-Hsing Li, Yunfeng Ding, Weijie Zhang, David G Edwards, Nan Chen, Azadeh Nasrazadani, Naoto T Ueno, Bora Lim, Xiang H-F Zhang

Faculty, Staff and Students Publications

Solid tumours induce systemic immunosuppression that involves myeloid and T cells. B cell-related mechanisms remain relatively understudied. Here we discover two distinct patterns of tumour-induced B cell abnormality (TiBA; TiBA-1 and TiBA-2), both associated with abnormal myelopoiesis in the bone marrow. TiBA-1 probably results from the niche competition between pre-progenitor-B cells and myeloid progenitors, leading to a global reduction in downstream B cells. TiBA-2 is characterized by systemic accumulation of a unique early B cell population, driven by interaction with excessive neutrophils. Importantly, TiBA-2-associated early B cells foster the systemic accumulation of exhaustion-like T cells. Myeloid and B cells from …


Car-Redirected Natural Killer T Cells Demonstrate Superior Antitumor Activity To Car-T Cells Through Multimodal Cd1d-Dependent Mechanisms, Gloria Delfanti, Ourania Tsahouridis, Caroline Marnata Pellegry, Manuela Zingarelli, Gatphan Atassi, Mark G Woodcock, Giulia Casorati, Paolo Dellabona, William Y Kim, Linjie Guo, Barbara Savoldo, Ageliki Tsagaratou, J Justin Milner, Leonid S Metelitsa, Gianpietro Dotti Nov 2024

Car-Redirected Natural Killer T Cells Demonstrate Superior Antitumor Activity To Car-T Cells Through Multimodal Cd1d-Dependent Mechanisms, Gloria Delfanti, Ourania Tsahouridis, Caroline Marnata Pellegry, Manuela Zingarelli, Gatphan Atassi, Mark G Woodcock, Giulia Casorati, Paolo Dellabona, William Y Kim, Linjie Guo, Barbara Savoldo, Ageliki Tsagaratou, J Justin Milner, Leonid S Metelitsa, Gianpietro Dotti

Faculty, Staff and Students Publications

Human natural killer T (NKT) cells have been proposed as a promising cell platform for chimeric antigen receptor (CAR) therapy in solid tumors. Here we generated murine CAR-NKT cells and compared them with CAR-T cells in immune-competent mice. Both CAR-NKT cells and CAR-T cells showed similar antitumor effects in vitro, but CAR-NKT cells showed superior antitumor activity in vivo via CD1d-dependent immune responses in the tumor microenvironment. Specifically, we show that CAR-NKT cells eliminate CD1d-expressing M2-like macrophages. In addition, CAR-NKT cells promote epitope spreading and activation of endogenous T cell responses against tumor-associated neoantigens. Finally, we observed that CAR-NKT cells …


Synaptic Plasticity In The Injured Brain Depends On The Temporal Pattern Of Stimulation, Carrie A Williams, Philip R Baldwin, Michael J Friedlander Nov 2024

Synaptic Plasticity In The Injured Brain Depends On The Temporal Pattern Of Stimulation, Carrie A Williams, Philip R Baldwin, Michael J Friedlander

Faculty, Staff and Students Publications

Neurostimulation protocols are increasingly used as therapeutic interventions, including for brain injury. In addition to the direct activation of neurons, these stimulation protocols are also likely to have downstream effects on those neurons' synaptic outputs. It is well known that alterations in the strength of synaptic connections (long-term potentiation, LTP; long-term depression, LTD) are sensitive to the frequency of stimulation used for induction; however, little is known about the contribution of the temporal pattern of stimulation to the downstream synaptic plasticity that may be induced by neurostimulation in the injured brain. We explored interactions of the temporal pattern and frequency …


Impact And Recovery Of Vha Epilepsy Care Services During The Covid-19 Pandemic, Alan Towne, Ann C Van Cott, Aatif Husain Nov 2024

Impact And Recovery Of Vha Epilepsy Care Services During The Covid-19 Pandemic, Alan Towne, Ann C Van Cott, Aatif Husain

Faculty, Staff and Students Publications

BACKGROUND: The Epilepsy Centers of Excellence (ECoE) is a network of facilities within the Veterans Health Administration that evaluates and treats veterans with epilepsy and seizure disorders. This article outlines how the COVID-19 pandemic impacted ECoE services and recovery.

METHODS: Directors of 17 ECoEs were surveyed 4 times between May 2020 and July 2022 on 5 domains: functioning of outpatient epilepsy clinics, outpatient electroencephalogram, epilepsy monitoring unit, anticipated permanent operational changes, and utility of national and local recommendations. Data on the spread of COVID-19 and administrative workload data were compared with the availability of epilepsy services.

RESULTS: There was an …


National Liver Cancer Screening Trial (Tracer) Study Protocol, Jorge A Marrero, Sneha Deodhar, Stephanie Page-Lester, Camden Lopez, Ziding Feng, Nabihah Tayob Nov 2024

National Liver Cancer Screening Trial (Tracer) Study Protocol, Jorge A Marrero, Sneha Deodhar, Stephanie Page-Lester, Camden Lopez, Ziding Feng, Nabihah Tayob

Faculty, Staff and Students Publications

BACKGROUND: Professional guidelines recommend HCC screening in at-risk patients using semi-annual ultrasound with or without alpha-fetoprotein (AFP); however, this strategy has limited effectiveness due to low adherence and sensitivity. Increasing data support the potential role of blood-based biomarker panels, which could improve both aspects. The biomarker panel GALAD, comprised of sex, age, and 3 blood biomarkers (AFP, AFP-L3, and des-carboxy prothrombin des-carboxy prothrombin), has shown high sensitivity and specificity in biomarker phase II (case-control) and phase III (retrospective cohort) validation studies. However, prospective validation in a large phase IV biomarker clinical utility trial is necessary before its adoption in practice. …


Genetic Risk Factors In Isolated Dystonia Escape Genome-Wide Association Studies, Tobias Reinberger, Lisa-Marie Nuxoll, Gamze Kilic-Berkmen, Joel S Perlmutter, Sebastian Loens, Carlos Cruchaga, Andre Franke, Valerija Dobricic, Frauke Hinrichs, Anne Grözinger, Eckart Altenmüller, Steven Bellows, Sylvia Boesch, Susan B Bressman, Kevin R Duque, Alberto J Espay, Andreas Ferbert, Jeanne S Feuerstein, Samuel Frank, Thomas Gasser, Bernhard Haslinger, Robert Jech, Frank Kaiser, Christoph Kamm, Katja Kollewe, Andrea A Kühn, Mark S Ledoux, Ebba Lohmann, Abhimanyu Mahajan, Alexander Münchau, Trisha Multhaupt-Buell, Alexander Pantelyat, Sarah E Pirio Richardson, Deborah Raymond, Stephen G Reich, Rachel Saunders Pullman, Barbara Schormair, Nutan Sharma, Azadeh Hamzehei Sichani, Kristina Simonyan, Jens Volkmann, Aparna Wagle Shukla, Juliane Winkelmann, Laura J Wright, Michael Zech, Kirsten E Zeuner, Simone Zittel, Meike Kasten, Yan V Sun, Tobias Bäumer, Norbert Brüggemann, Laurie J Ozelius, Hyder A Jinnah, Christine Klein, Inke R König Nov 2024

Genetic Risk Factors In Isolated Dystonia Escape Genome-Wide Association Studies, Tobias Reinberger, Lisa-Marie Nuxoll, Gamze Kilic-Berkmen, Joel S Perlmutter, Sebastian Loens, Carlos Cruchaga, Andre Franke, Valerija Dobricic, Frauke Hinrichs, Anne Grözinger, Eckart Altenmüller, Steven Bellows, Sylvia Boesch, Susan B Bressman, Kevin R Duque, Alberto J Espay, Andreas Ferbert, Jeanne S Feuerstein, Samuel Frank, Thomas Gasser, Bernhard Haslinger, Robert Jech, Frank Kaiser, Christoph Kamm, Katja Kollewe, Andrea A Kühn, Mark S Ledoux, Ebba Lohmann, Abhimanyu Mahajan, Alexander Münchau, Trisha Multhaupt-Buell, Alexander Pantelyat, Sarah E Pirio Richardson, Deborah Raymond, Stephen G Reich, Rachel Saunders Pullman, Barbara Schormair, Nutan Sharma, Azadeh Hamzehei Sichani, Kristina Simonyan, Jens Volkmann, Aparna Wagle Shukla, Juliane Winkelmann, Laura J Wright, Michael Zech, Kirsten E Zeuner, Simone Zittel, Meike Kasten, Yan V Sun, Tobias Bäumer, Norbert Brüggemann, Laurie J Ozelius, Hyder A Jinnah, Christine Klein, Inke R König

Faculty, Staff and Students Publications

Background: Despite considerable heritability, previous smaller genome-wide association studies (GWASs) have not identified any robust genetic risk factors for isolated dystonia.

Objective: The objective of this study was to perform a large-scale GWAS in a well-characterized, multicenter sample of >6000 individuals to identify genetic risk factors for isolated dystonia.

Methods: Array-based GWASs were performed on autosomes for 4303 dystonia participants and 2362 healthy control subjects of European ancestry with subgroup analysis based on age at onset, affected body regions, and a newly developed clinical score. Another 736 individuals were used for validation.

Results: This GWAS identified no common genome-wide significant …


Identifying High-Risk Multiple Myeloma Patients: A Novel Approach Using A Clonal Gene Signature Nov 2024

Identifying High-Risk Multiple Myeloma Patients: A Novel Approach Using A Clonal Gene Signature

Faculty, Staff and Students Publications

Multiple myeloma (MM) is a heterogeneous disease with a small subset of high-risk patients having poor prognoses. Identifying these patients is crucial for treatment management and strategic decisions. In this study, we developed a novel computational framework to define prognostic gene signatures by selecting genes with expression driven by clonal copy number alterations. We applied this framework to MM and developed a clonal gene signature (CGS) consisting of 22 genes and evaluated in five independent datasets. The CGS provided significant prognostic values after adjusting for well-established factors including cytogenetic abnormalities, International Staging System (ISS), and Revised ISS (R-ISS). Importantly, CGS …


Vagus Nerve Stimulation Recruits The Central Cholinergic System To Enhance Perceptual Learning, Kathleen A Martin, Eleni S Papadoyannis, Jennifer K Schiavo, Saba Shokat Fadaei, Habon A Issa, Soomin C Song, Sofia Orrey Valencia, Nesibe Z Temiz, Matthew J Mcginley, David A Mccormick, Robert C Froemke Nov 2024

Vagus Nerve Stimulation Recruits The Central Cholinergic System To Enhance Perceptual Learning, Kathleen A Martin, Eleni S Papadoyannis, Jennifer K Schiavo, Saba Shokat Fadaei, Habon A Issa, Soomin C Song, Sofia Orrey Valencia, Nesibe Z Temiz, Matthew J Mcginley, David A Mccormick, Robert C Froemke

Duncan NRI Faculty and Staff Publications

Perception can be refined by experience, up to certain limits. It is unclear whether perceptual limits are absolute or could be partially overcome via enhanced neuromodulation and/or plasticity. Recent studies suggest that peripheral nerve stimulation, specifically vagus nerve stimulation (VNS), can alter neural activity and augment experience-dependent plasticity, although little is known about central mechanisms recruited by VNS. Here we developed an auditory discrimination task for mice implanted with a VNS electrode. VNS applied during behavior gradually improved discrimination abilities beyond the level achieved by training alone. Two-photon imaging revealed VNS induced changes to auditory cortical responses and activated cortically …


Loss-Of-Function In Rbbp5 Results In A Syndromic Neurodevelopmental Disorder Associated With Microcephaly, Jijun Wan, Sharayu V Jangam, Odelia Chorin, Annick Rothschild, Ortal Barel, Milena Mariani, Maria Iascone, Han Xue, Undiagnosed Diseases Network, Jing Huang, Cyril Mignot, Boris Keren, Virginie Saillour, Annelise Y Mah-Som, Stephanie Sacharow, Farrah Rajabi, Carrie Costin, Shinya Yamamoto, Oguz Kanca, Hugo J Bellen, Jill A Rosenfeld, Christina G S Palmer, Stanley F Nelson, Michael F Wangler, Julian A Martinez-Agosto Nov 2024

Loss-Of-Function In Rbbp5 Results In A Syndromic Neurodevelopmental Disorder Associated With Microcephaly, Jijun Wan, Sharayu V Jangam, Odelia Chorin, Annick Rothschild, Ortal Barel, Milena Mariani, Maria Iascone, Han Xue, Undiagnosed Diseases Network, Jing Huang, Cyril Mignot, Boris Keren, Virginie Saillour, Annelise Y Mah-Som, Stephanie Sacharow, Farrah Rajabi, Carrie Costin, Shinya Yamamoto, Oguz Kanca, Hugo J Bellen, Jill A Rosenfeld, Christina G S Palmer, Stanley F Nelson, Michael F Wangler, Julian A Martinez-Agosto

Faculty, Staff and Students Publications

PURPOSE: Epigenetic dysregulation has been associated with many inherited disorders. RBBP5 (HGNC:9888) encodes a core member of the protein complex that methylates histone 3 lysine-4 and has not been implicated in human disease.

METHODS: We identify 5 unrelated individuals with de novo heterozygous variants in RBBP5. Three nonsense/frameshift and 2 missense variants were identified in probands with neurodevelopmental symptoms, including global developmental delay, intellectual disability, microcephaly, and short stature. Here, we investigate the pathogenicity of the variants through protein structural analysis and transgenic Drosophila models.

RESULTS: Both missense p.(T232I) and p.(E296D) variants affect evolutionarily conserved amino acids located at the …


An Artificial Intelligence-Generated Model Predicts 90-Day Survival In Alcohol-Associated Hepatitis: A Global Cohort Study, Douglas A Simonetto, Luis A Díaz, Francisco Idalsoaga, Gustavo Ayares, Jorge Arnold, María Ayala-Valverde, Diego Perez, Jaime Gomez, Rodrigo Escarate, Eduardo Fuentes-López, Carolina Ramirez-Cadiz, Dalia Morales-Arraez, Wei Zhang, Steve Qian, Joseph C Ahn, Seth Buryska, Heer Mehta, Nicholas Dunn, Muhammad Waleed, Horia Stefanescu, Andreea Bumbu, Adelina Horhat, Bashar Attar, Rohit Agrawal, Joaquín Cabezas, Victor Echavaría, Berta Cuyàs, Maria Poca, German Soriano, Shiv K Sarin, Rakhi Maiwall, Prasun K Jalal, Fátima Higuera-De-La-Tijera, Anand V Kulkarni, P Nagaraja Rao, Patricia Guerra-Salazar, Lubomir Skladaný, Natália Kubánek, Veronica Prado, Ana Clemente-Sanchez, Diego Rincon, Tehseen Haider, Kristina R Chacko, Gustavo A Romero, Florencia D Pollarsky, Juan C Restrepo, Luis G Toro, Pamela Yaquich, Manuel Mendizabal, Maria L Garrido, Sebastián Marciano, Melisa Dirchwolf, Victor Vargas, César Jiménez, David Hudson, Guadalupe García-Tsao, Guillermo Ortiz, Juan G Abraldes, Patrick S Kamath, Marco Arrese, Vijay H Shah, Ramon Bataller, Juan Pablo Arab Nov 2024

An Artificial Intelligence-Generated Model Predicts 90-Day Survival In Alcohol-Associated Hepatitis: A Global Cohort Study, Douglas A Simonetto, Luis A Díaz, Francisco Idalsoaga, Gustavo Ayares, Jorge Arnold, María Ayala-Valverde, Diego Perez, Jaime Gomez, Rodrigo Escarate, Eduardo Fuentes-López, Carolina Ramirez-Cadiz, Dalia Morales-Arraez, Wei Zhang, Steve Qian, Joseph C Ahn, Seth Buryska, Heer Mehta, Nicholas Dunn, Muhammad Waleed, Horia Stefanescu, Andreea Bumbu, Adelina Horhat, Bashar Attar, Rohit Agrawal, Joaquín Cabezas, Victor Echavaría, Berta Cuyàs, Maria Poca, German Soriano, Shiv K Sarin, Rakhi Maiwall, Prasun K Jalal, Fátima Higuera-De-La-Tijera, Anand V Kulkarni, P Nagaraja Rao, Patricia Guerra-Salazar, Lubomir Skladaný, Natália Kubánek, Veronica Prado, Ana Clemente-Sanchez, Diego Rincon, Tehseen Haider, Kristina R Chacko, Gustavo A Romero, Florencia D Pollarsky, Juan C Restrepo, Luis G Toro, Pamela Yaquich, Manuel Mendizabal, Maria L Garrido, Sebastián Marciano, Melisa Dirchwolf, Victor Vargas, César Jiménez, David Hudson, Guadalupe García-Tsao, Guillermo Ortiz, Juan G Abraldes, Patrick S Kamath, Marco Arrese, Vijay H Shah, Ramon Bataller, Juan Pablo Arab

Faculty, Staff and Students Publications

Background and aims: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model.

Approach and results: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) …


A Cross-Systems Primer For Synthetic Microbial Communities, Laila P Partida-Martinez, Kathryn A Patras, Marie Simonin, Britt Koskella Nov 2024

A Cross-Systems Primer For Synthetic Microbial Communities, Laila P Partida-Martinez, Kathryn A Patras, Marie Simonin, Britt Koskella

Faculty, Staff and Students Publications

The design and use of synthetic communities, or SynComs, is one of the most promising strategies for disentangling the complex interactions within microbial communities, and between these communities and their hosts. Compared to natural communities, these simplified consortia provide the opportunity to study ecological interactions at tractable scales, as well as facilitating reproducibility and fostering interdisciplinary science. However, the effective implementation of the SynCom approach requires several important considerations regarding the development and application of these model systems. There are also emerging ethical considerations when both designing and deploying SynComs in clinical, agricultural or environmental settings. Here we outline current …


Asn Kidney Health Guidance On The Management Of Obesity In Persons Living With Kidney Diseases, Alex R Chang, Allon N Friedman, Meera N Harhay, Elizabeth Yakes Jimenez, Brandon Kistler, Aleksandra Kukla, Kristin Larson, Lindamarie U Lavenburg, Sankar Dass Navaneethan, John Ortiz, Rocio I Pereira, David B Sarwer, Philip R Schauer, Evan M Zeitler Nov 2024

Asn Kidney Health Guidance On The Management Of Obesity In Persons Living With Kidney Diseases, Alex R Chang, Allon N Friedman, Meera N Harhay, Elizabeth Yakes Jimenez, Brandon Kistler, Aleksandra Kukla, Kristin Larson, Lindamarie U Lavenburg, Sankar Dass Navaneethan, John Ortiz, Rocio I Pereira, David B Sarwer, Philip R Schauer, Evan M Zeitler

Faculty, Staff and Students Publications

No abstract provided.


Transcriptomic And Epigenomic Signatures Distinguish High- And Low-Risk Endotypes For Liver Tumor Development, Amrit Koirala, Micah B Castillo, Preethi H Gunaratne, Cristian Coarfa, Cheryl L Walker Nov 2024

Transcriptomic And Epigenomic Signatures Distinguish High- And Low-Risk Endotypes For Liver Tumor Development, Amrit Koirala, Micah B Castillo, Preethi H Gunaratne, Cristian Coarfa, Cheryl L Walker

Faculty, Staff and Students Publications

The epigenome is a target for environmental exposures and a potential determinant of inter-individual differences in response. In genetically identical C57Bl/6 mice exposed from gestation to weaning to the endocrine-disrupting chemical (EDC) tributyltin (TBT), hepatic tumor development later in life varied across multiple cohorts over time and depending on sex and diet. In one cohort where approximately half of TBT-exposed male mice developed liver tumors at 10 months (Katz et al. Hepatic tumor formation in adult mice developmentally exposed to organotin, Environmental Health Perspectives, 128 (1), 17010, 2020), transcriptomic (RNA-seq) and epigenomic (ChIP-seq) profiling was performed on blood and liver …


Residential Proximity To Oil And Gas Developments And Childhood Cancer Survival, Maria I Castellanos, Jeremy M Schraw, Elyse Burgess, Erin C Peckham-Gregory, Abiodun O Oluyomi, Michael E Scheurer, Amy E Hughes, Philip J Lupo Nov 2024

Residential Proximity To Oil And Gas Developments And Childhood Cancer Survival, Maria I Castellanos, Jeremy M Schraw, Elyse Burgess, Erin C Peckham-Gregory, Abiodun O Oluyomi, Michael E Scheurer, Amy E Hughes, Philip J Lupo

Faculty, Staff and Students Publications

Background: Environmental toxicants may impact survival in children with cancer, but the literature investigating these associations remains limited. Because oil and gas developments emit several hazardous air pollutants, the authors evaluated the relationship between residential proximity to oil or gas development and survival across 21 different pediatric cancers.

Methods: The Texas Cancer Registry had 29,730 children (≤19 years old) diagnosed with a primary cancer between 1995 to 2017. Geocoded data were available for 285,266 active oil or gas wells and 109,965 horizontal wells. The authors calculated whether each case lived within 1000 m (yes/no) from each type of oil or …


Pak3 Exacerbates Cardiac Lipotoxicity Via Srebp1c In Obesity Cardiomyopathy, Xinyi Chen, Andrea Ruiz-Velasco, Zhiyong Zou, Susanne S Hille, Claire Ross, Oveena Fonseka, Sanskruti R Gare, Nasser Hawimel O Alatawi, Rida Raja, Jiayan Zhang, Namrita Kaur, Xiangjun Zhao, Henrietta Morrell-Davies, Jessica M Miller, Riham R E Abouleisa, Qinghui Ou, Derk Frank, Martin K Rutter, Christian Pinali, Tao Wang, Tamer M A Mohamed, Oliver J Müller, Wei Liu Nov 2024

Pak3 Exacerbates Cardiac Lipotoxicity Via Srebp1c In Obesity Cardiomyopathy, Xinyi Chen, Andrea Ruiz-Velasco, Zhiyong Zou, Susanne S Hille, Claire Ross, Oveena Fonseka, Sanskruti R Gare, Nasser Hawimel O Alatawi, Rida Raja, Jiayan Zhang, Namrita Kaur, Xiangjun Zhao, Henrietta Morrell-Davies, Jessica M Miller, Riham R E Abouleisa, Qinghui Ou, Derk Frank, Martin K Rutter, Christian Pinali, Tao Wang, Tamer M A Mohamed, Oliver J Müller, Wei Liu

Faculty, Staff and Students Publications

Obesity-induced lipid overload in cardiomyocytes contributes to profound oxidative stress and cardiomyopathy, culminating in heart failure. In this study, we investigate a novel mechanism whereby lipids accumulate in cardiomyocytes, and seek the relevant treatment strategies. P21-activated kinase 3 (PAK3) was elevated in obese human myocardium, and the murine hearts and cardiomyocytes upon diet- or fatty acid-induced stress, respectively. Mice with cardiac-specific overexpression of PAK3 were more susceptible to the development of cardiac dysfunction upon diet stress, at least partially, because of increased deposition of toxic lipids within the myocardium. Mechanistically, PAK3 promoted the nuclear expression of sterol regulatory element binding …


Dna Methylation Classes Of Stage Ii And Iii Primary Melanomas And Their Clinical And Prognostic Significance, Allison Reiner, David L Corcoran, Ronglai Shen, Eloise A Parrish, Honglin Hao, Lan Lin, Jessica M Kenney, Gbemisola Ilelaboye, Caroline E Kostrzewa, Pei Fen Kuan, Klaus J Busam, Cecilia Lezcano, Tim K Lee, Eva Hernando, Paul B Googe, David W Ollila, Stergios Moschos, Ivan Gorlov, Christopher I Amos, Marc S Ernstoff, Anne E Cust, James S Wilmott, Richard A Scolyer, Graham J Mann, Ismael A Vergara, Jennifer Ko, Judy R Rees, Shaofeng Yan, Eduardo Nagore, Marcus Bosenberg, Bonnie Gould Rothberg, Iman Osman, Jeffrey E Lee, Yvonne Saenger, Paul Bogner, Cheryl L Thompson, Meg Gerstenblith, Sheri L Holmen, Pauline Funchain, Elise Brunsgaard, Natalie D Depcik-Smith, Li Luo, Tawny Boyce, Irene Orlow, Colin B Begg, Marianne Berwick, Nancy E Thomas Nov 2024

Dna Methylation Classes Of Stage Ii And Iii Primary Melanomas And Their Clinical And Prognostic Significance, Allison Reiner, David L Corcoran, Ronglai Shen, Eloise A Parrish, Honglin Hao, Lan Lin, Jessica M Kenney, Gbemisola Ilelaboye, Caroline E Kostrzewa, Pei Fen Kuan, Klaus J Busam, Cecilia Lezcano, Tim K Lee, Eva Hernando, Paul B Googe, David W Ollila, Stergios Moschos, Ivan Gorlov, Christopher I Amos, Marc S Ernstoff, Anne E Cust, James S Wilmott, Richard A Scolyer, Graham J Mann, Ismael A Vergara, Jennifer Ko, Judy R Rees, Shaofeng Yan, Eduardo Nagore, Marcus Bosenberg, Bonnie Gould Rothberg, Iman Osman, Jeffrey E Lee, Yvonne Saenger, Paul Bogner, Cheryl L Thompson, Meg Gerstenblith, Sheri L Holmen, Pauline Funchain, Elise Brunsgaard, Natalie D Depcik-Smith, Li Luo, Tawny Boyce, Irene Orlow, Colin B Begg, Marianne Berwick, Nancy E Thomas

Faculty, Staff and Students Publications

Purpose: Patients with stage II and III cutaneous primary melanoma vary considerably in their risk of melanoma-related death. We explore the ability of methylation profiling to distinguish primary melanoma methylation classes and their associations with clinicopathologic characteristics and survival.

Materials and methods: InterMEL is a retrospective case-control study that assembled primary cutaneous melanomas from American Joint Committee on Cancer (AJCC) 8th edition stage II and III patients diagnosed between 1998 and 2015 in the United States and Australia. Cases are patients who died of melanoma within 5 years from original diagnosis. Controls survived longer than 5 years without evidence of …


Xenomake: A Pipeline For Processing And Sorting Xenograft Reads From Spatial Transcriptomic Experiments, Gloria V Echeverria, Qian Zhu Nov 2024

Xenomake: A Pipeline For Processing And Sorting Xenograft Reads From Spatial Transcriptomic Experiments, Gloria V Echeverria, Qian Zhu

Faculty, Staff and Students Publications

SUMMARY: Xenograft models are attractive models that mimic human tumor biology and permit one to perturb the tumor microenvironment and study its drug response. Spatially resolved transcriptomics (SRT) provides a powerful way to study the organization of xenograft models, but currently there is a lack of specialized pipeline for processing xenograft reads originated from SRT experiments. Xenomake is a standalone pipeline for the automated handling of spatial xenograft reads. Xenomake handles read processing, alignment, xenograft read sorting, and connects well with downstream spatial analysis packages. We additionally show that Xenomake can correctly assign organism-specific reads, reduce sparsity of data by …


Metabolites Link Intake Of A Healthy Diet To Better Insulin And Glucose Homeostasis In The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Elizabeth T Jensen, Gautam Ramesh, Alain G Bertoni, Stephen S Rich, Yii-Der I Chen, David M Herrington, Jerome I Rotter, Mark O Goodarzi Nov 2024

Metabolites Link Intake Of A Healthy Diet To Better Insulin And Glucose Homeostasis In The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Elizabeth T Jensen, Gautam Ramesh, Alain G Bertoni, Stephen S Rich, Yii-Der I Chen, David M Herrington, Jerome I Rotter, Mark O Goodarzi

Faculty, Staff and Students Publications

BACKGROUND: Dietary quality has been linked to better glycemic control, but the precise molecular mechanisms giving rise to these associations are not fully understood.

OBJECTIVES: To examine the association of metabolites associated with the intake of a healthy diet with measures of insulin/glucose homeostasis.

METHODS: Using cross-sectional data from 295 United States adults, the associations between 3 diet pattern scores and metabolome-wide metabolites were estimated via linear regression models, which controlled for demographic factors and health behaviors. Subsequently, the associations between the diet-related metabolites with 6 measures of glucose/insulin homeostasis were examined in similar models. A Bonferroni correction was applied …


Prognostic Stratification In Dlbcl Patients With Aberrant Myc Gene, Yong Li, Christopher I Amos, Chao Cheng Nov 2024

Prognostic Stratification In Dlbcl Patients With Aberrant Myc Gene, Yong Li, Christopher I Amos, Chao Cheng

Faculty, Staff and Students Publications

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by a subset of patients who exhibit treatment resistance and poor prognoses. Genomic assays have been widely employed to identify high-risk individuals characterized by rearrangements in the MYC, BCL2 and BCL6 genes. These patients typically undergo more aggressive therapeutic treatments; however, there remains a significant variation in their treatment outcomes. This study introduces an MYC signature score (MYCSS) derived from gene expression profiles, specifically designed to evaluate MYC overactivation in DLBCL patients. MYCSS was validated across several independent cohorts to assess its ability to stratify patients based on MYC-related genetic …


Eyelid Reconstruction, Matthew J Parham, Austin Y Jiang, Katherine J Williams, Amy S Xue Nov 2024

Eyelid Reconstruction, Matthew J Parham, Austin Y Jiang, Katherine J Williams, Amy S Xue

Faculty, Staff and Students Publications

Reconstruction of the eyelid is a complex process that requires an understanding of eyelid anatomy and various reconstructive techniques to restore function and appearance. The eyelids, essential for globe protection, moisture retention, and expression, contain the lacrimal system and intricate musculature that make reconstruction challenging. Tumor excision commonly results in defects in the eyelid that require careful reconstructive planning, with consideration for defect dimensions, location, and involvement of surrounding tissue. This review presents reconstructive techniques commonly used in the management of eyelid defects.


Spontaneous Rupture Of A Splenic Artery Aneurysm With Hemoperitoneum; Case Presentation, Vlad Denis Constantin, Ion Motofei, Gelu Valentin Stefanescu, Adrian Silaghi Oct 2024

Spontaneous Rupture Of A Splenic Artery Aneurysm With Hemoperitoneum; Case Presentation, Vlad Denis Constantin, Ion Motofei, Gelu Valentin Stefanescu, Adrian Silaghi

Journal of Mind and Medical Sciences

Aneurysms of the splenic artery are relatively rare, being found in patients with portal hypertension, multiparous, atherosclerosis, or in young people with various genetic diseases. In the uncomplicated forms, splenic artery aneurysms are often difficult to diagnose either because of the asymptomatic evolution, or because of the non-specific symptoms. In cases of trauma or large sizes, aneurysms can be complicated by rupture, which can cause hemoperitoneum with the risk of death if specific treatment is not initiated as soon as possible. Depending on the location of the splenic aneurysm, comorbidities, the patient's general condition or life-threatening complications, laparotomy, laparoscopy, endovascular …


The Role Of Computed Tomography And Esophageal Ultrasonography In The Preoperative Evaluation Of Esophageal Cancer Resection, Vasile Cosmin Obleaga, Dan Ionuț Gheonea, Ioana Andreea Gheonea, Cecil Sorin Mirea, Emil Moraru, Mihai Călin Ciorbagiu, Ionică Daniel Vîlcea, Tiberiu Ștefăniță Cojan-Țenea Oct 2024

The Role Of Computed Tomography And Esophageal Ultrasonography In The Preoperative Evaluation Of Esophageal Cancer Resection, Vasile Cosmin Obleaga, Dan Ionuț Gheonea, Ioana Andreea Gheonea, Cecil Sorin Mirea, Emil Moraru, Mihai Călin Ciorbagiu, Ionică Daniel Vîlcea, Tiberiu Ștefăniță Cojan-Țenea

Journal of Mind and Medical Sciences

Objectives. Esophageal cancer is one of the most aggressive types of cancer, with a 5-year relative survival rate of only 18%-20.5%. Survival is highly dependent on accurate positive diagnosis and staging, in which the imaging modalities available have a primary role. The study is focused on the analysis of the preoperative T and M staging strategy and the reliability of computed tomography and endoscopic esophageal ultrasound in predicting resectability. A second objective was to evaluate the influence of preoperative imaging modalities on decreasing the number of unnecessary thoracotomies and laparotomies. Material and Methods. This study was conducted on a lot …


Magnetic Resonance Used As A Differential Diagnostic Tool Between Inflammatory Cancer Of The Sigmoid And Acute Sigmoid Diverticulitis, Cornel Dragos Cheregi, Teodora Gabriela Alexescu, Andrei Vasile Pascalau, Ovidiu Laurean Pop, Calin Magheru, Ioana Maria Muresan, Nicoleta Ramona Suciu, Maur Sebastian Horgos, Mihai Stefan Muresan Oct 2024

Magnetic Resonance Used As A Differential Diagnostic Tool Between Inflammatory Cancer Of The Sigmoid And Acute Sigmoid Diverticulitis, Cornel Dragos Cheregi, Teodora Gabriela Alexescu, Andrei Vasile Pascalau, Ovidiu Laurean Pop, Calin Magheru, Ioana Maria Muresan, Nicoleta Ramona Suciu, Maur Sebastian Horgos, Mihai Stefan Muresan

Journal of Mind and Medical Sciences

Sigmoid diverticulitis is a common disease characterized by a well-standardized diagnostic approach and treatment. Colorectal cancer is the third most common malignancy worldwide, irrespective of gender. In 2020, CRC global-related mortality rate was estimated at 935 173 cases, with an incidence of 9.3% in men and 9.5% in women. The diagnosis of acute diverticulitis is always made by performing a contrast-enhanced-computed tomography (CT) of the abdomen. Current diagnosis guidelines do not recommend the use of a magnetic resonance imaging (MRI) for further and more precise assessment of a suspected sigmoid diverticulitis diagnosed by CT. Early lower-gastrointestinal (lower-GI) endoscopy is rarely …


Approaches And Indications In Laparoscopic Choledoscopy, Iulian Slavu, Raluca Tulin, Ileana Dima, Alexandru Dogaru, Florin Filipoiu, Bogdan Socea, Anca Monica Oprescu Macovei, Adrian Tulin Oct 2024

Approaches And Indications In Laparoscopic Choledoscopy, Iulian Slavu, Raluca Tulin, Ileana Dima, Alexandru Dogaru, Florin Filipoiu, Bogdan Socea, Anca Monica Oprescu Macovei, Adrian Tulin

Journal of Mind and Medical Sciences

Objectives. Up to 20% of patients with biliary lithiasis have bile duct stones, which are asymptomatic in 50% of cases. The aim of the study was to evaluate the role of choledoscopy in extracting stones from the main bile ducts. Materials and Methods. This is a retrospective study (January 2014 - December 2024) on 2309 patients who underwent a laparoscopic cholecystectomy. Laparoscopic choledoscopy was performed in 32 cases. Of the 32 patients with complete clearance, none had residual common bile duct stones (CBDS) at 1 year postoperatively. Results. The ideal approach in our study was the transcystic approach, with the …


Effects Of The Covid-19 Pandemic On Clinical Manifestations And Therapeutic Outcomes In Acute Endophthalmitis, Ana Maria Dascalu, Sanda Jurja, Carmen Luminita Mocanu, Cristina Alexandrescu, Daniela Stana, Madalina Totir, Ece Ergin, Corneliu Tudor, Catalin Cicerone Grigorescu, Dragos Serban, Laurentiu Simion, Dan Dumitrescu, Andrei Marin, Catalin Teodor Constantinescu, Bogdan Mihai Cristea Oct 2024

Effects Of The Covid-19 Pandemic On Clinical Manifestations And Therapeutic Outcomes In Acute Endophthalmitis, Ana Maria Dascalu, Sanda Jurja, Carmen Luminita Mocanu, Cristina Alexandrescu, Daniela Stana, Madalina Totir, Ece Ergin, Corneliu Tudor, Catalin Cicerone Grigorescu, Dragos Serban, Laurentiu Simion, Dan Dumitrescu, Andrei Marin, Catalin Teodor Constantinescu, Bogdan Mihai Cristea

Journal of Mind and Medical Sciences

Endophthalmitis incidence and clinical characteristics was reported to change during Covid-19 pandemic, due to multiple influencing factors, such as prolonged lockdown periods, persistent immune suppression following Sars-Cov-2 infection, and mask wearing. We conducted a retrospective eight-year study, during January 2016 and December 2023, that aims to investigates the differences in terms of etiology, clinical characteristics and outcomes in cases with acute endophthalmitis, admitted before (2016-2019) and during Covid-19 pandemic (2020-2023). The two study subgroups were homogenous in term of age, gender distribution, associated comorbidities, and addressability. During Covid-19 pandemic there were significant delays in presentation (p=0.02), more cases of endogenous …


Infertility As A Possible Multifactorial Condition; The Experience Of A Single Center, Cristina-Diana Popescu, Bashar Haj Hamoud, Romina Marina Sima, Anca Bobirca, Oana Denisa Balalau, Mihaela Amza, Romeo Micu, Gabriel Petre Gorecki, Liana Ples Oct 2024

Infertility As A Possible Multifactorial Condition; The Experience Of A Single Center, Cristina-Diana Popescu, Bashar Haj Hamoud, Romina Marina Sima, Anca Bobirca, Oana Denisa Balalau, Mihaela Amza, Romeo Micu, Gabriel Petre Gorecki, Liana Ples

Journal of Mind and Medical Sciences

Objectives. Infertility is a topic of great interest around the world because it affects many couples at young ages. It can be caused by genetic background, associated with pathologies and/or external factors. The purpose of our study was to identify the causes of infertility of women presented in our clinic with this pathology. Materials and Methods. This retrospective study was performed on women with primary or secondary infertility. The analyzed data were age, weight, hereditary and personal pathological history, medication, menstrual cycle characteristics, standard blood tests, ultrasound, hysterosalpingography and hysteroscopy. Results. The study included 204 women with average age 35 …


Evaluation Of Short-Term Complications In Laparoscopic Peritoneal Dialysis Catheter Placement - A Single Tertiary Center Experience, Cristina Raluca Iorga, Iuliana Andreiana, Simona Hildegrad Stancu, Traian Constantin, Victor Strambu, Cristian Iorga Oct 2024

Evaluation Of Short-Term Complications In Laparoscopic Peritoneal Dialysis Catheter Placement - A Single Tertiary Center Experience, Cristina Raluca Iorga, Iuliana Andreiana, Simona Hildegrad Stancu, Traian Constantin, Victor Strambu, Cristian Iorga

Journal of Mind and Medical Sciences

Background. Peritoneal dialysis is a form of kidney function replacement that is not as widespread as hemodialysis. However, it has recognized advantages, such as preservation of residual renal function, lack of vascular access, and the ability to be performed at home. On the other hand, it requires the correct insertion of a peritoneal dialysis (PD) catheter and maintaining its patency. Methods. We conducted a retrospective study of 126 patients with end-stage renal disease who underwent laparoscopic Tenckhoff catheter placement for peritoneal dialysis between January 2016 and December 2022. The study analyzed the frequency and type of complications registered within three …