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Full-Text Articles in Medical Specialties

Dlk-Dependent Axonal Mitochondrial Fission Drives Degeneration After Axotomy, Jorge Gómez-Deza, Matthew Nebiyou, Mor R Alkaslasi, Francisco M Nadal-Nicolás, Preethi Somasundaram, Anastasia L Slavutsky, Wei Li, Michael E Ward, Trent A Watkins, Claire E Le Pichon Dec 2024

Dlk-Dependent Axonal Mitochondrial Fission Drives Degeneration After Axotomy, Jorge Gómez-Deza, Matthew Nebiyou, Mor R Alkaslasi, Francisco M Nadal-Nicolás, Preethi Somasundaram, Anastasia L Slavutsky, Wei Li, Michael E Ward, Trent A Watkins, Claire E Le Pichon

Faculty, Staff and Students Publications

Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma. We demonstrate that this apoptotic wave is locally initiated in the axon by dual leucine zipper kinase (DLK). We find that mitochondrial fission and resultant cell death are entirely dependent on phosphorylation of dynamin related …


Orthogonal And Multiplexable Genetic Perturbations With An Engineered Prime Editor And A Diverse Rna Array, Qichen Yuan, Hongzhi Zeng, Tyler C Daniel, Qingzhuo Liu, Yongjie Yang, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Liliana M Abramson, Boyang Zhang, Yong Xu, Xue Gao Dec 2024

Orthogonal And Multiplexable Genetic Perturbations With An Engineered Prime Editor And A Diverse Rna Array, Qichen Yuan, Hongzhi Zeng, Tyler C Daniel, Qingzhuo Liu, Yongjie Yang, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Liliana M Abramson, Boyang Zhang, Yong Xu, Xue Gao

Faculty, Staff and Students Publications

Programmable and modular systems capable of orthogonal genomic and transcriptomic perturbations are crucial for biological research and treating human genetic diseases. Here, we present the minimal versatile genetic perturbation technology (mvGPT), a flexible toolkit designed for simultaneous and orthogonal gene editing, activation, and repression in human cells. The mvGPT combines an engineered compact prime editor (PE), a fusion activator MS2-p65-HSF1 (MPH), and a drive-and-process multiplex array that produces RNAs tailored to different types of genetic perturbation. mvGPT can precisely edit human genome via PE coupled with a prime editing guide RNA and a nicking guide RNA, activate endogenous gene expression …


Unravelling An Unusual Blastoma In An Infant With Confusing Radiological Diagnosis, Arun Viswanathan Dr, Santosh Rai, Harsha Prasad Lashkari, Jayateertha Joshi Dec 2024

Unravelling An Unusual Blastoma In An Infant With Confusing Radiological Diagnosis, Arun Viswanathan Dr, Santosh Rai, Harsha Prasad Lashkari, Jayateertha Joshi

Manipal Journal of Medical Sciences

We report an unusual case of an 8-month-old child, who presented to us with a mass per abdomen with confusing imaging characteristics reported as a germ cell tumour / Neuroblastoma.

Patient presented with a large mass per abdomen which had both retroperitoneal and intraperitoneal components and was compressing the adjacent structures and was appearing heterogenous with calcifications within. The more favoured diagnosis on imaging was a peritoneal or retroperitoneal germ cell tumor / Neuroblastoma. Repeated imaging revealed that the mass was abutting / compressing the left lobe of the liver and high AFP beta HCG and LDH values were noted. …


Cultivating Compassion: A Cross-Sectional Evaluation Of Empathy Among Medical Undergraduate Students, Anchu R Nath, Ishika Jindal, Nayanabai Shabadi, Sunil Kumar D Dec 2024

Cultivating Compassion: A Cross-Sectional Evaluation Of Empathy Among Medical Undergraduate Students, Anchu R Nath, Ishika Jindal, Nayanabai Shabadi, Sunil Kumar D

Digital Journal of Clinical Medicine

ABSTRACT:

BACKGROUND: Empathy plays a crucial role in medical practice, profoundly affecting patient outcomes and treatment. Understanding the factors that influence empathy among medical students can help in developing strategies to enhance empathetic skills during medical training. This study aims to evaluate the correlates of empathy among medical undergraduate students using an epidemiological cross-sectional design.

MATERIALS AND METHODS:

A cross-sectional study was conducted among 270 medical undergraduate students from various academic years at JSS Medical College for four months (September 2023-December 2023). Convenient sampling was used to select study participants. Participants completed a standardized empathy questionnaire, the Jefferson Scale …


The Win Ratio Approach In Bayesian Monitoring For Two-Arm Phase Ii Clinical Trial Designs With Multiple Time-To-Event Endpoints, Xinran Huang, Jian Wang, Jing Ning Dec 2024

The Win Ratio Approach In Bayesian Monitoring For Two-Arm Phase Ii Clinical Trial Designs With Multiple Time-To-Event Endpoints, Xinran Huang, Jian Wang, Jing Ning

Faculty, Staff and Student Publications

To assess the preliminary therapeutic impact of a novel treatment, futility monitoring is commonly employed in Phase II clinical trials to facilitate informed decisions regarding the early termination of trials. Given the rapid evolution in cancer treatment development, particularly with new agents like immunotherapeutic agents, the focus has often shifted from objective response to time-to-event endpoints. In trials involving multiple time-to-event endpoints, existing monitoring designs typically select one as the primary endpoint or employ a composite endpoint as the time to the first occurrence of any event. However, relying on a single efficacy endpoint may not adequately evaluate an experimental …


Double-Blind Randomised Trial Of Saline Solution For Gargling And Nasal Rinsing In Sars-Cov-2 Infection, Sebastian R Espinoza, Lexton Trauffler, Amir Shamshirsaz, Alireza Shamshirsaz, Andres Espinoza, Jimmy Espinoza, Alice O'Brien Dec 2024

Double-Blind Randomised Trial Of Saline Solution For Gargling And Nasal Rinsing In Sars-Cov-2 Infection, Sebastian R Espinoza, Lexton Trauffler, Amir Shamshirsaz, Alireza Shamshirsaz, Andres Espinoza, Jimmy Espinoza, Alice O'Brien

Faculty, Staff and Student Publications

Background: Previous studies have shown that hypertonic saline nasal irrigation and gargling reduced the duration of symptoms in upper respiratory infections caused by coronavirus. This study aims to investigate the effects of two saline regimens on symptoms associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Methods: Between 2020 and 2022, individuals aged 18-65 years who tested positive for SARS-CoV-2 infection via polymerase chain reaction (PCR) were randomly assigned to either low- or high-saline regimens for 14 days. The low-saline solutions contained 2.13 g of salt dissolved in eight ounces of warm water, while the high-saline solution contained six grams of …


Nos Inhibition Sensitizes Metaplastic Breast Cancer To Pi3k Inhibition And Taxane Therapy Via C-Jun Repression, Tejaswini Reddy, Akshjot Puri, Liliana Guzman-Rojas, Christoforos Thomas, Wei Qian, Jianying Zhou, Hong Zhao, Bijan Mahboubi, Adrian Oo, Young-Jae Cho, Baek Kim, Jose Thaiparambil, Roberto Rosato, Karina Ortega Martinez, Maria Florencia Chervo, Camila Ayerbe, Noah Giese, David Wink, Stephen Lockett, Stephen Wong, Jeffrey Chang, Savitri Krishnamurthy, Clinton Yam, Stacy Moulder, Helen Piwnica-Worms, Funda Meric-Bernstam, Jenny Chang Dec 2024

Nos Inhibition Sensitizes Metaplastic Breast Cancer To Pi3k Inhibition And Taxane Therapy Via C-Jun Repression, Tejaswini Reddy, Akshjot Puri, Liliana Guzman-Rojas, Christoforos Thomas, Wei Qian, Jianying Zhou, Hong Zhao, Bijan Mahboubi, Adrian Oo, Young-Jae Cho, Baek Kim, Jose Thaiparambil, Roberto Rosato, Karina Ortega Martinez, Maria Florencia Chervo, Camila Ayerbe, Noah Giese, David Wink, Stephen Lockett, Stephen Wong, Jeffrey Chang, Savitri Krishnamurthy, Clinton Yam, Stacy Moulder, Helen Piwnica-Worms, Funda Meric-Bernstam, Jenny Chang

Faculty, Staff and Student Publications

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane. Mechanistically, NOS blockade leads to a decrease in the S-nitrosylation of c-Jun NH


Bayesian Nonparametric Model For Heterogeneous Treatment Effects With Zero-Inflated Data, Chanmin Kim, Yisheng Li, Ting Xu, Zhongxing Liao Dec 2024

Bayesian Nonparametric Model For Heterogeneous Treatment Effects With Zero-Inflated Data, Chanmin Kim, Yisheng Li, Ting Xu, Zhongxing Liao

Faculty, Staff and Student Publications

One goal of precision medicine is to develop effective treatments for patients by tailoring to their individual demographic, clinical, and/or genetic characteristics. To achieve this goal, statistical models must be developed that can identify and evaluate potentially heterogeneous treatment effects in a robust manner. The oft-cited existing methods for assessing treatment effect heterogeneity are based upon parametric models with interactions or conditioning on covariate values, the performance of which is sensitive to the omission of important covariates and/or the choice of their values. We propose a new Bayesian nonparametric (BNP) method for estimating heterogeneous causal effects in studies with zero-inflated …


Role Of Nf2 Mutation In The Development Of Eleven Different Cancers, Shervin Hosseingholi Nouri, Vijay Nitturi, Elizabeth Ledbetter, Collin W English, Sean Lau, Tiemo J Klisch, Akash J Patel Dec 2024

Role Of Nf2 Mutation In The Development Of Eleven Different Cancers, Shervin Hosseingholi Nouri, Vijay Nitturi, Elizabeth Ledbetter, Collin W English, Sean Lau, Tiemo J Klisch, Akash J Patel

Faculty, Staff and Students Publications

Background/Objectives: With the rise in prevalence of diagnostic genetic techniques like RNA sequencing and whole exome sequencing (WES), as well as biological treatment regiments for cancer therapy, several genes have been implicated in carcinogenesis. This review aims to update our understanding of the Neurofibromatosis 2 (NF2) gene and its role in the pathogenesis of various cancers. Methods: A comprehensive search of five online databases yielded 43 studies that highlighted the effect of sporadic NF2 mutations on several cancers, including sporadic meningioma, ependymoma, schwannoma, mesothelioma, breast cancer, hepatocellular carcinoma, prostate cancer, glioblastoma, thyroid cancer, and melanoma. Of note were key biological …


Aperiodic Spectral Slope Tracks The Effects Of Brain State On Saliency Responses In The Human Auditory Cortex, Madaline Mocchi, Eleonora Bartoli, John Magnotti, Jan Willem De Gee, Brian Metzger, Bailey Pascuzzi, Raissa Mathura, Suhruthaa Pulapaka, Wayne Goodman, Sameer Sheth, Matthew J Mcginley, Kelly Bijanki Dec 2024

Aperiodic Spectral Slope Tracks The Effects Of Brain State On Saliency Responses In The Human Auditory Cortex, Madaline Mocchi, Eleonora Bartoli, John Magnotti, Jan Willem De Gee, Brian Metzger, Bailey Pascuzzi, Raissa Mathura, Suhruthaa Pulapaka, Wayne Goodman, Sameer Sheth, Matthew J Mcginley, Kelly Bijanki

Faculty, Staff and Students Publications

Alteration of responses to salient stimuli occurs in a wide range of brain disorders and may be rooted in pathophysiological brain state dynamics. Specifically, tonic and phasic modes of activity in the reticular activating system (RAS) influence, and are influenced by, salient stimuli, respectively. The RAS influences the spectral characteristics of activity in the neocortex, shifting the balance between low- and high-frequency fluctuations. Aperiodic '1/f slope' has emerged as a promising composite measure of these brain state dynamics. However, the relationship of 1/f slope to state-dependent processes, such as saliency, is less explored, particularly intracranially in humans. Here, we record …


Parp Inhibition Radiosensitizes Brca1 Wildtype And Mutated Breast Cancer To Proton Therapy, Mariam Ben Kacem, Scott J Bright, Emma Moran, David B Flint, David K J Martinus, Broderick X Turner, Ilsa Qureshi, Rishab Kolachina, Mandira Manandhar, Poliana C Marinello, Simona F Shaitelman, Gabriel O Sawakuchi Dec 2024

Parp Inhibition Radiosensitizes Brca1 Wildtype And Mutated Breast Cancer To Proton Therapy, Mariam Ben Kacem, Scott J Bright, Emma Moran, David B Flint, David K J Martinus, Broderick X Turner, Ilsa Qureshi, Rishab Kolachina, Mandira Manandhar, Poliana C Marinello, Simona F Shaitelman, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Aggressive breast cancers often fail or acquire resistance to radiotherapy. To develop new strategies to improve the outcome of aggressive breast cancer patients, we studied how PARP inhibition radiosensitizes breast cancer models to proton therapy, which is a radiotherapy modality that generates more DNA damage in the tumor than standard radiotherapy using photons. Two human BRCA1-mutated breast cancer cell lines and their isogenic BRCA1-recovered pairs were treated with a PARP inhibitor and irradiated with photons or protons. Protons (9.9 and 3.85 keV/µm) induced higher cell kill independent of BRCA1 status. PARP inhibition amplified the cell kill effect to both photons …


Cancer Organoids As Reliable Disease Models To Drive Clinical Development Of Novel Therapies, Giovanni Blandino, Ronit Satchi-Fainaro, Ingeborg Tinhofer, Giovanni Tonon, Sarah C Heilshorn, Yong-Jun Kwon, Ana Pestana, Carlotta Frascolla, Luca Pompili, Aurora Puce, Sara Iachettini, Annalisa Tocci, Sofia Karkampouna, Marianna Kruithof-De Julio, Piera Tocci, Nicla Porciello, Klizia Maccaroni, Daniela Rutigliano, Xiling Shen, Gennaro Ciliberto Dec 2024

Cancer Organoids As Reliable Disease Models To Drive Clinical Development Of Novel Therapies, Giovanni Blandino, Ronit Satchi-Fainaro, Ingeborg Tinhofer, Giovanni Tonon, Sarah C Heilshorn, Yong-Jun Kwon, Ana Pestana, Carlotta Frascolla, Luca Pompili, Aurora Puce, Sara Iachettini, Annalisa Tocci, Sofia Karkampouna, Marianna Kruithof-De Julio, Piera Tocci, Nicla Porciello, Klizia Maccaroni, Daniela Rutigliano, Xiling Shen, Gennaro Ciliberto

Faculty, Staff and Student Publications

On September 23-24 (2024) the 6th Workshop IRE on Translational Oncology, titled "Cancer Organoids as Reliable Disease Models to Drive Clinical Development of Novel Therapies," took place at the IRCCS Regina Elena Cancer Institute in Rome. This prominent international conference focused on tumor organoids, bringing together leading experts from around the world.A central challenge in precision oncology is modeling the dynamic tumor ecosystem, which encompasses numerous elements that evolve spatially and temporally. Patient-derived 3D culture models, including organoids, explants, and engineered or bioprinted systems, have recently emerged as sophisticated tools capable of capturing the complexity and diversity of cancer cells …


Optimizing Ewing Sarcoma And Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement, Matthew S Dietz, Alyaa Al-Ibraheemi, Jessica L Davis, C Matthew Hawkins, Brian T Craig, Roshni Dasgupta, David S Geller, David S Shulman, Sarah Cohen-Gogo, Ajay Gupta, Susan L Whiteway, Emily K Slotkin, Christine M Heske, Safia K Ahmed, Daniel J Indelicato, Catherine M Albert, Nicole Montgomery, Jesse K Sandberg, Holcombe E Grier, Mark Krailo, Michael S Isakoff, Elyssa Rubin, Elizabeth R Lawlor, Steven G Dubois, Leo Mascarenhas, Patrick J Grohar, Odion Binitie, Damon Reed, Katherine Janeway, Ryan D Roberts, Kelly M Bailey Dec 2024

Optimizing Ewing Sarcoma And Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement, Matthew S Dietz, Alyaa Al-Ibraheemi, Jessica L Davis, C Matthew Hawkins, Brian T Craig, Roshni Dasgupta, David S Geller, David S Shulman, Sarah Cohen-Gogo, Ajay Gupta, Susan L Whiteway, Emily K Slotkin, Christine M Heske, Safia K Ahmed, Daniel J Indelicato, Catherine M Albert, Nicole Montgomery, Jesse K Sandberg, Holcombe E Grier, Mark Krailo, Michael S Isakoff, Elyssa Rubin, Elizabeth R Lawlor, Steven G Dubois, Leo Mascarenhas, Patrick J Grohar, Odion Binitie, Damon Reed, Katherine Janeway, Ryan D Roberts, Kelly M Bailey

Faculty, Staff and Students Publications

Trends in diagnostic biopsy sample collection approaches for primary bone sarcomas have shifted in the past 2 decades. Although open/incisional biopsies used to be the predominant approach to obtain diagnostic material for Ewing sarcoma and osteosarcoma, image-guided core needle biopsies have increased in frequency and are safe for patients. These procedures are less invasive and reduce recovery times but have potential limitations. The quantity and quality of tissue obtained through these procedures vary between institutions. Acquired viable tissue volumes can be low, limiting the conduct of downstream expanded clinical workup, molecular analyses, and research. Patients with advanced Ewing sarcoma and …


Prolonged Cardiopulmonary Bypass Time-Induced Endothelial Dysfunction Via Glypican-1 Shedding, Inflammation, And Matrix Metalloproteinase 9 In Patients Undergoing Cardiac Surgery, Shiyi Li, Katherine V Nordick, Iván Murrieta-Álvarez, Randall P Kirby, Rishav Bhattacharya, Ismael Garcia, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal Dec 2024

Prolonged Cardiopulmonary Bypass Time-Induced Endothelial Dysfunction Via Glypican-1 Shedding, Inflammation, And Matrix Metalloproteinase 9 In Patients Undergoing Cardiac Surgery, Shiyi Li, Katherine V Nordick, Iván Murrieta-Álvarez, Randall P Kirby, Rishav Bhattacharya, Ismael Garcia, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

OBJECTIVES: A prolonged cardiopulmonary bypass (CPB) time of over 180 min is linked to poorer outcomes and higher mortality in cardiac surgery. This study examines how glypican-1 shedding, matrix metallopeptidase 9 (MMP9), and the pro-inflammatory cytokine IL-1β may contribute to endothelial dysfunction in patients undergoing on-pump surgery with an extended CPB.

METHODS: Fifty-one patients undergoing cardiac surgical procedures were divided into two groups based on the intraoperative CPB duration: (i) normal CPB (<180 >min,

RESULTS: Before surgery, the plasma levels of glypican-1, MMP9, and IL-1β were comparable between the normal CPB and the prolonged CPB groups. However, after the end …


High-Intensity Focused Ultrasound Ablation For Primary Or Salvage Prostate Cancer Therapy: Initial Outcomes In The Veteran Healthcare Setting, Sagar Patel, Ali Antar, Aly Alrabaa, Gal Saffati, Broderick Fleming, Neel Srikishen, Jeremy Slawin, Jennifer Taylor, Jeffrey Jones Dec 2024

High-Intensity Focused Ultrasound Ablation For Primary Or Salvage Prostate Cancer Therapy: Initial Outcomes In The Veteran Healthcare Setting, Sagar Patel, Ali Antar, Aly Alrabaa, Gal Saffati, Broderick Fleming, Neel Srikishen, Jeremy Slawin, Jennifer Taylor, Jeffrey Jones

Faculty, Staff and Students Publications

High-Intensity Focused Ultrasound (HIFU) provides comparable oncologic, erectile, and urinary outcomes to standard-of-care options for localized prostate cancer. This study reports the largest United States series of HIFU in veterans for both primary and salvage therapies. We retrospectively analyzed the outcomes of 43 veterans treated at the Michael E. DeBakey Veterans Affairs Medical Center from 2018 to 2022. Primary endpoints included prostate-specific antigen (PSA) reduction and local recurrence rates. Secondary endpoints included 30-day complications, Sexual Health Inventory for Men (SHIM), and American Urological Association Symptom Score (AUASS). In our study, 31 veterans (72.1%) received primary treatment and 12 (27.9%) received …


Stem Cell Activity-Coupled Suppression Of Endogenous Retrovirus Governs Adult Tissue Regeneration, Ying Lyu, Soo Jin Kim, Ericka S Humphrey, Richa Nayak, Yinglu Guan, Qingnan Liang, Kun Hee Kim, Yukun Tan, Jinzhuang Dou, Huandong Sun, Xingzhi Song, Priyadharsini Nagarajan, Kamryn N Gerner-Mauro, Kevin Jin, Virginia Liu, Rehman H Hassan, Miranda L Johnson, Lisa P Deliu, Yun You, Anurag Sharma, H Amalia Pasolli, Yue Lu, Jianhua Zhang, Vakul Mohanty, Ken Chen, Youn Joo Yang, Taiping Chen, Yejing Ge Dec 2024

Stem Cell Activity-Coupled Suppression Of Endogenous Retrovirus Governs Adult Tissue Regeneration, Ying Lyu, Soo Jin Kim, Ericka S Humphrey, Richa Nayak, Yinglu Guan, Qingnan Liang, Kun Hee Kim, Yukun Tan, Jinzhuang Dou, Huandong Sun, Xingzhi Song, Priyadharsini Nagarajan, Kamryn N Gerner-Mauro, Kevin Jin, Virginia Liu, Rehman H Hassan, Miranda L Johnson, Lisa P Deliu, Yun You, Anurag Sharma, H Amalia Pasolli, Yue Lu, Jianhua Zhang, Vakul Mohanty, Ken Chen, Youn Joo Yang, Taiping Chen, Yejing Ge

Faculty, Staff and Student Publications

Mammalian retrotransposons constitute 40% of the genome. During tissue regeneration, adult stem cells coordinately repress retrotransposons and activate lineage genes, but how this coordination is controlled is poorly understood. Here, we observed that dynamic expression of histone methyltransferase SETDB1 (a retrotransposon repressor) closely mirrors stem cell activities in murine skin. SETDB1 ablation leads to the reactivation of endogenous retroviruses (ERVs, a type of retrotransposon) and the assembly of viral-like particles, resulting in hair loss and stem cell exhaustion that is reversible by antiviral drugs. Mechanistically, at least two molecularly and spatially distinct pathways are responsible: antiviral defense mediated by hair …


Multisociety Endorsement Of The 2024 European Guideline Recommendations On Coronary Revascularization, Victor Dayan, Joseph F Sabik, Minoru Ono, Marc Ruel, Song Wan, Lars G Svensson, Leonard N Girardi, Y Joseph Woo, Vinay Badhwar, Marc R Moon, Wilson Y Szeto, Vinod H Thourani, Rui M S Almeida, Zhe Zheng, Walter J Gomes, Dawn S Hui, Rosemary F Kelly, Miguel Sousa Uva, Joanna Chikwe, Faisal G Bakaeen Dec 2024

Multisociety Endorsement Of The 2024 European Guideline Recommendations On Coronary Revascularization, Victor Dayan, Joseph F Sabik, Minoru Ono, Marc Ruel, Song Wan, Lars G Svensson, Leonard N Girardi, Y Joseph Woo, Vinay Badhwar, Marc R Moon, Wilson Y Szeto, Vinod H Thourani, Rui M S Almeida, Zhe Zheng, Walter J Gomes, Dawn S Hui, Rosemary F Kelly, Miguel Sousa Uva, Joanna Chikwe, Faisal G Bakaeen

Faculty, Staff and Students Publications

No abstract provided.


Artificial Intelligence In Fetal And Pediatric Echocardiography, Alan Wang, Tam T Doan, Charitha Reddy, Pei-Ni Jone Dec 2024

Artificial Intelligence In Fetal And Pediatric Echocardiography, Alan Wang, Tam T Doan, Charitha Reddy, Pei-Ni Jone

Faculty, Staff and Students Publications

Echocardiography is the main modality in diagnosing acquired and congenital heart disease (CHD) in fetal and pediatric patients. However, operator variability, complex image interpretation, and lack of experienced sonographers and cardiologists in certain regions are the main limitations existing in fetal and pediatric echocardiography. Advances in artificial intelligence (AI), including machine learning (ML) and deep learning (DL), offer significant potential to overcome these challenges by automating image acquisition, image segmentation, CHD detection, and measurements. Despite these promising advancements, challenges such as small number of datasets, algorithm transparency, physician comfort with AI, and accessibility must be addressed to fully integrate AI …


Multiparametric Cardiovascular Magnetic Resonance Is Associated With Outcomes In Pediatric Heart Transplant Recipients, Andrew A Lawson, Kae Watanabe, Lindsay Griffin, Christina Laternser, Michael Markl, Cynthia K Rigsby, Joshua D Robinson, Nazia Husain Dec 2024

Multiparametric Cardiovascular Magnetic Resonance Is Associated With Outcomes In Pediatric Heart Transplant Recipients, Andrew A Lawson, Kae Watanabe, Lindsay Griffin, Christina Laternser, Michael Markl, Cynthia K Rigsby, Joshua D Robinson, Nazia Husain

Faculty, Staff and Students Publications

BACKGROUND: Multiparametric cardiovascular magnetic resonance (CMR) has an emerging role in non-invasive surveillance of pediatric heart transplant recipients (PHTR). Higher myocardial T2, higher extracellular volume fraction (ECV), and late gadolinium enhancement (LGE) have been associated with adverse clinical outcomes in adult heart transplant recipients. The purpose of this study was to investigate the prognostic value of CMR-derived T1 and T2 mapping, ECV, and LGE for clinical outcomes in PHTR.

METHODS: We performed a single-center, retrospective chart review of consecutive, gadolinium-enhanced CMR studies in PHTR over a 7.5-year period, excluding follow-up studies. Standard CMR ventricular volume and function analysis, T1 mapping …


Impact Of American Thyroid Association's Revised Cancer Management Guidelines On Thyroid Cancer Incidence Trends: A Retrospective Cohort Study, 2000-2020, Pierre Fwelo, Natalia I Heredia, Ruosha Li, Ayrton Bangolo, Vignesh K Nagesh, Simcha Weissman, Xianglin L Du Dec 2024

Impact Of American Thyroid Association's Revised Cancer Management Guidelines On Thyroid Cancer Incidence Trends: A Retrospective Cohort Study, 2000-2020, Pierre Fwelo, Natalia I Heredia, Ruosha Li, Ayrton Bangolo, Vignesh K Nagesh, Simcha Weissman, Xianglin L Du

Faculty, Staff and Student Publications

Background: The past four decades have seen a steady increase in thyroid cancer in the United States (US). This study investigated the impact of the American Thyroid Association (ATA)'s revised cancer management guidelines on thyroid cancer incidence trends and how the trends varied by socioeconomic, histologic, geographic, and racial and ethnic characteristics from 2000 to 2020.

Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) database to identify thyroid cancer cases diagnosed among US patients between 2000 and 2020. We employed joinpoint regression software to fit, assess, and compare thyroid cancer incidence trends over time stratified by …


High Peripheral T Cell Diversity Is Associated With Lower Risk Of Toxicity And Superior Response To Dual Immune Checkpoint Inhibitor Therapy In Patients With Metastatic Nsclc, Mehmet Altan, Ruoxing Li, Ziyi Li, Runzhe Chen, Ajay Sheshadri, Hai T Tran, Latasha Little, Joshua Baguley, Jefferson Sinson, Natalie Vokes, Saumil Gandhi, Mara B Antonoff, Stephen G Swisher, Greg Lizee, Alexandre Reuben, John V Heymach, Jianjun Zhang Dec 2024

High Peripheral T Cell Diversity Is Associated With Lower Risk Of Toxicity And Superior Response To Dual Immune Checkpoint Inhibitor Therapy In Patients With Metastatic Nsclc, Mehmet Altan, Ruoxing Li, Ziyi Li, Runzhe Chen, Ajay Sheshadri, Hai T Tran, Latasha Little, Joshua Baguley, Jefferson Sinson, Natalie Vokes, Saumil Gandhi, Mara B Antonoff, Stephen G Swisher, Greg Lizee, Alexandre Reuben, John V Heymach, Jianjun Zhang

Faculty, Staff and Student Publications

INTRODUCTION: Despite significant successes, immune checkpoint blockade fails to achieve clinical responses in a significant proportion of patients, predictive markers for responses are imperfect and immune-related adverse events (irAEs) are unpredictable. We used T-cell receptor (TCR) sequencing to systematically analyze prospectively collected patient blood samples from a randomized clinical trial of dual immune checkpoint inhibitor therapy to evaluate changes in the T-cell repertoire and their association with response and irAEs.

METHODS: Patients with immunotherapy-naïve metastatic non-small cell lung cancer (NSCLC) were treated with ipilimumab and nivolumab according to trial protocol (LONESTAR, NCT03391869). Blood samples were systematically obtained at baseline (n=107), …


Targeted Degradation Of Oncogenic Krasg12v Triggers Antitumor Immunity In Lung Cancer Models, Dezhi Li, Ke Geng, Yuan Hao, Jiajia Gu, Saurav Kumar, Annabel T Olson, Christina C Kuismi, Hye Mi Kim, Yuanwang Pan, Fiona Sherman, Asia M Williams, Yiting Li, Fei Li, Ting Chen, Cassandra Thakurdin, Michela Ranieri, Mary Meynardie, Daniel S Levin, Janaye Stephens, Alison Chafitz, Joy Chen, Mia S Donald-Paladino, Jaylen M Powell, Ze-Yan Zhang, Wei Chen, Magdalena Ploszaj, Han Han, Shengqing Stan Gu, Tinghu Zhang, Baoli Hu, Benjamin A Nacev, Medard Ernest Kaiza, Alice H Berger, Xuerui Wang, Jing Li, Xuejiao Sun, Yang Liu, Xiaoyang Zhang, Tullia C Bruno, Nathanael S Gray, Behnam Nabet, Kwok-Kin Wong, Hua Zhang Dec 2024

Targeted Degradation Of Oncogenic Krasg12v Triggers Antitumor Immunity In Lung Cancer Models, Dezhi Li, Ke Geng, Yuan Hao, Jiajia Gu, Saurav Kumar, Annabel T Olson, Christina C Kuismi, Hye Mi Kim, Yuanwang Pan, Fiona Sherman, Asia M Williams, Yiting Li, Fei Li, Ting Chen, Cassandra Thakurdin, Michela Ranieri, Mary Meynardie, Daniel S Levin, Janaye Stephens, Alison Chafitz, Joy Chen, Mia S Donald-Paladino, Jaylen M Powell, Ze-Yan Zhang, Wei Chen, Magdalena Ploszaj, Han Han, Shengqing Stan Gu, Tinghu Zhang, Baoli Hu, Benjamin A Nacev, Medard Ernest Kaiza, Alice H Berger, Xuerui Wang, Jing Li, Xuejiao Sun, Yang Liu, Xiaoyang Zhang, Tullia C Bruno, Nathanael S Gray, Behnam Nabet, Kwok-Kin Wong, Hua Zhang

Faculty, Staff and Student Publications

Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most frequently mutated oncogene in lung adenocarcinoma, with G12C and G12V being the most predominant forms. Recent breakthroughs in KRASG12C inhibitors have transformed the clinical management of patients with the G12C mutation and advanced our understanding of the function of this mutation. However, little is known about the targeted disruption of KRASG12V, partly due to a lack of specific inhibitors. Here, we leverage the degradation tag (dTAG) system to develop a KRASG12V-transgenic mouse model. We explored the therapeutic potential of KRASG12V degradation and characterized its effect on the tumor microenvironment (TME). …


Use Of Cigarettes And E-Cigarettes, Impulsivity, And Anxiety: Influences On Suicidal Ideation Among Youth And Young Adults In Texas, Anna V Wilkinson, Baojiang Chen, Alan C Swann, David P Graham, David A Nielsen, Thomas R Kosten, Alexandra Loukas, Dale S Mantey, Bara S Bataineh, Melissa B Harrell Dec 2024

Use Of Cigarettes And E-Cigarettes, Impulsivity, And Anxiety: Influences On Suicidal Ideation Among Youth And Young Adults In Texas, Anna V Wilkinson, Baojiang Chen, Alan C Swann, David P Graham, David A Nielsen, Thomas R Kosten, Alexandra Loukas, Dale S Mantey, Bara S Bataineh, Melissa B Harrell

Faculty, Staff and Students Publications

Introduction: Cigarette use and smoking intensity increase risk of suicidal ideation. Less is known about e-cigarette use. Here we examine direct influences of cigarette versus e-cigarette use on suicidal ideation among 16- to 23-year-olds in Texas.

Aims and methods: Since 2019, the Texas Adolescent Tobacco and Marketing Surveillance Study collected data on suicidal ideation every 6 months covering the previous 2 weeks. Youths answering that they had "thoughts that you would be better off dead, or of hurting yourself" on more than 2 of 14 days were categorized as having suicidal ideation. Generalized linear mixed-effects logistic regressions examined the influence …


Global Prevalence Of Helicobacter Pylori Antibiotic Resistance Among Children In The World Health Organization Regions Between 2000 And 2023: A Systematic Review And Meta-Analysis, Aryan Salahi-Niri, Ali Nabavi-Rad, Tanya Marie Monaghan, Theodore Rokkas, Michael Doulberis, Amir Sadeghi, Mohammad Reza Zali, Yoshio Yamaoka, Evelina Tacconelli, Abbas Yadegar Dec 2024

Global Prevalence Of Helicobacter Pylori Antibiotic Resistance Among Children In The World Health Organization Regions Between 2000 And 2023: A Systematic Review And Meta-Analysis, Aryan Salahi-Niri, Ali Nabavi-Rad, Tanya Marie Monaghan, Theodore Rokkas, Michael Doulberis, Amir Sadeghi, Mohammad Reza Zali, Yoshio Yamaoka, Evelina Tacconelli, Abbas Yadegar

Faculty, Staff and Students Publications

Background: Helicobacter pylori infection causes gastritis, peptic ulcers, and gastric cancer. The infection is typically acquired in childhood and persists throughout life. The major impediment to successful therapy is antibiotic resistance. This systematic review and meta-analysis aimed to comprehensively assess the global prevalence of antibiotic resistance in pediatric H. pylori infection.

Methods: We performed a systematic search of publication databases that assessed H. pylori resistance rates to clarithromycin, metronidazole, levofloxacin, amoxicillin, and tetracycline in children. The WHO region classification was used to group pooled primary and secondary resistance estimates along with 95% confidence interval (CI). H. pylori antibiotic resistance rates …


The Role Of The Triglyceride-Glucose Index As A Biomarker Of Cardio-Metabolic Syndromes, Verena Gounden, Sridevi Devaraj, Ishwarlal Jialal Dec 2024

The Role Of The Triglyceride-Glucose Index As A Biomarker Of Cardio-Metabolic Syndromes, Verena Gounden, Sridevi Devaraj, Ishwarlal Jialal

Faculty, Staff and Students Publications

BACKGROUND: The Triglyceride-glucose (TyG) index represents a simple, cost-effective, and valid proxy for insulin resistance. This surrogate marker has also been proposed as a predictor of metabolic and cardiovascular disease (CVD). In this descriptive review, we aimed to assess the utility of the TyG index as a predictive biomarker of cardiometabolic diseases.

METHODS: A search was conducted in PubMed, and Web of Science to identify cross-sectional and more importantly prospective studies examining the use of the TyG index as a predictive biomarker. The following terms were utilized in addition to the TyG index: "insulin resistance", "metabolic syndrome", "diabetes"; "cardiovascular diseases". …


Relative Survival, Conditional Survival, And Causes Of Death In Patients With Early Gastric Cancer, With A Focus On Differences Between Cardia And Non-Cardia Cancer, Anas Elgenidy, Omar Alomari, Mohamed Marey Hesn, Anas Khaled, Sarah A Nada, Mostafa Elsayed, Ali Mahmoud, Mohammed Al-Mahdi Al-Kurdi, Ahmed M Afifi, George Cholankeril Dec 2024

Relative Survival, Conditional Survival, And Causes Of Death In Patients With Early Gastric Cancer, With A Focus On Differences Between Cardia And Non-Cardia Cancer, Anas Elgenidy, Omar Alomari, Mohamed Marey Hesn, Anas Khaled, Sarah A Nada, Mostafa Elsayed, Ali Mahmoud, Mohammed Al-Mahdi Al-Kurdi, Ahmed M Afifi, George Cholankeril

Faculty, Staff and Students Publications

Background: Many researchers believe that cardia (CGC) and non-cardia (NCGC) are two different types of tumors, having different features like incidence rate, risk factors, geographical location, and socioeconomic status. This study aims to investigate the causes of death (COD) survival rates among early gastric cancer patients with a focus on differences between CGC and NCGC.

Methods: This retrospective study employed SEER*stat software (version 8.3.92) to analyze the SEER 17 plus dataset (2000–2019). Standardized mortality ratios (SMR) were computed. Relative survival and conditional survival post-diagnosis were calculated using R software (version 4.1.0) among the different subgroups.

Results: Within the follow-up period, …


International Workshop: What Is Needed To Ensure Outcome Measures For Rett Syndrome Are Fit-For-Purpose For Clinical Trials? June 7, 2023, Nashville, Usa, Jenny Downs, Dominique C Pichard, Walter E Kaufmann, Joseph P Horrigan, Melissa Raspa, Gillian Townend, Eric D Marsh, Helen Leonard, Kathleen Motil, Andrew C Dietz, Nupur Garg, Amitha Ananth, Breanne Byiers, Sarika Peters, Christopher Beatty, Frank Symons, Aleksandra Jacobs, James Youakim, Bernhard Suter, Paramola Santosh, Jeffrey L Neul, Tim A Benke Dec 2024

International Workshop: What Is Needed To Ensure Outcome Measures For Rett Syndrome Are Fit-For-Purpose For Clinical Trials? June 7, 2023, Nashville, Usa, Jenny Downs, Dominique C Pichard, Walter E Kaufmann, Joseph P Horrigan, Melissa Raspa, Gillian Townend, Eric D Marsh, Helen Leonard, Kathleen Motil, Andrew C Dietz, Nupur Garg, Amitha Ananth, Breanne Byiers, Sarika Peters, Christopher Beatty, Frank Symons, Aleksandra Jacobs, James Youakim, Bernhard Suter, Paramola Santosh, Jeffrey L Neul, Tim A Benke

Faculty, Staff and Students Publications

INTRODUCTION: The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.

METHODS: Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted. The clinical outcome assessments measured clinical severity, functional abilities, comorbidities and quality of life, and …


Inhibition Of Microrna-660-5p Decreases Breast Cancer Progression Through Direct Targeting Of Tmem41b, Valeria Villarreal-García, José Roberto Estupiñan-Jiménez, Vianey Gonzalez-Villasana, Pablo E Vivas-Mejía, Marienid Flores-Colón, Irma Estefanía Ancira-Moreno, Patricio Adrián Zapata-Morín, Claudia Altamirano-Torres, José Manuel Vázquez-Guillen, Cristina Rodríguez-Padilla, Recep Bayraktar, Mohamed H Rashed, Cristina Ivan, Gabriel Lopez-Berestein, Diana Reséndez-Pérez Dec 2024

Inhibition Of Microrna-660-5p Decreases Breast Cancer Progression Through Direct Targeting Of Tmem41b, Valeria Villarreal-García, José Roberto Estupiñan-Jiménez, Vianey Gonzalez-Villasana, Pablo E Vivas-Mejía, Marienid Flores-Colón, Irma Estefanía Ancira-Moreno, Patricio Adrián Zapata-Morín, Claudia Altamirano-Torres, José Manuel Vázquez-Guillen, Cristina Rodríguez-Padilla, Recep Bayraktar, Mohamed H Rashed, Cristina Ivan, Gabriel Lopez-Berestein, Diana Reséndez-Pérez

Faculty, Staff and Student Publications

Background: Breast cancer is the most prevalent cancer among women worldwide. Most breast cancer-related deaths result from metastasis and drug resistance. Novel therapies are imperative for targeting metastatic and drug-resistant breast cancer cells. Accumulating evidence suggests that dysregulated microRNAs (miRNAs) promote breast cancer progression, metastasis, and drug resistance. Compared with healthy breast tissue, miR-660-5p is notably overexpressed in breast cancer tumor tissues. However, the downstream effectors of miR-660-5p in breast cancer cells have not been fully elucidated. Our aim was to investigate the role of miR-660-5p in breast cancer cell proliferation, migration, invasion, and angiogenesis and to identify its potential …


Phenotypic And Genetic Heterogeneity Of A Pakistani Cohort Of 15 Consanguineous Families Segregating Variants In Leber Congenital Amaurosis-Associated Genes, Zainab Akhtar, Sumaira Altaf, Yumei Li, Sana Bibi, Jamal Shah, Kiran Afshan, Meng Wang, Hafiz Muhammad Jafar Hussain, Nadeem Qureshi, Rui Chen, Sabika Firasat Dec 2024

Phenotypic And Genetic Heterogeneity Of A Pakistani Cohort Of 15 Consanguineous Families Segregating Variants In Leber Congenital Amaurosis-Associated Genes, Zainab Akhtar, Sumaira Altaf, Yumei Li, Sana Bibi, Jamal Shah, Kiran Afshan, Meng Wang, Hafiz Muhammad Jafar Hussain, Nadeem Qureshi, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Background: Leber congenital amaurosis (LCA) is a congenital onset severe form of inherited retinal dystrophy (IRD) and a common cause of pediatric blindness. Disease-causing variants in at least 14 genes are reported to predispose LCA phenotype. LCA is inherited as an autosomal recessive disease. It can be an isolated eye disorder or as part of a syndrome, such as Senior Loken or Joubert syndrome. Sequencing studies from consanguineous populations have proven useful for novel variants identification; thus, the present study aimed to explore the genetic heterogeneity of 15 consanguineous Pakistani families, each segregating a severe IRD phenotype using targeted next …


Irregular Assessment Times In Pragmatic Randomized Clinical Trials, Andrea Apter, Frances K Barg, Sanjib Basu, Alex Federman, Winifred J Hamilton, Jerry A Krishnan, Tianjing Li, Russell Localio, Christine Pindle, Daniel O Scharfstein, Justin D Smith, Kaharu Sumino Dec 2024

Irregular Assessment Times In Pragmatic Randomized Clinical Trials, Andrea Apter, Frances K Barg, Sanjib Basu, Alex Federman, Winifred J Hamilton, Jerry A Krishnan, Tianjing Li, Russell Localio, Christine Pindle, Daniel O Scharfstein, Justin D Smith, Kaharu Sumino

Faculty, Staff and Students Publications

Deviation from protocolized assessment times is commonplace in pragmatic randomized clinical trials. Working with a stakeholder advisory board for a Patient-Centered Outcomes Research Institute®-funded project on statistical methods for handling potential biases introduced by irregular assessment times, we identified reasons for off-schedule or missed assessments. We used the Consolidated Framework for Implementation Research 2.0 to organize our findings. We conjectured that timely completion of outcome assessments is a function of multiple determinants, only some related to participants' health status. We identified potential determinants that can be modified during the protocol design stage and can be reassessed and mitigated during trial …