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Articles 5071 - 5100 of 7722

Full-Text Articles in Medicine and Health Sciences

Proteogenomic Data And Resources For Pan-Cancer Analysis, Yize Li, Yongchao Dou, Felipe Da Veiga Leprevost, Yifat Geffen, Anna P Calinawan, François Aguet, Yo Akiyama, Shankara Anand, Chet Birger, Song Cao, Rekha Chaudhary, Padmini Chilappagari, Marcin Cieslik, Antonio Colaprico, Daniel Cui Zhou, Corbin Day, Marcin J Domagalski, Myvizhi Esai Selvan, David Fenyö, Steven M Foltz, Alicia Francis, Tania Gonzalez-Robles, Zeynep H Gümüş, David Heiman, Michael Holck, Runyu Hong, Yingwei Hu, Eric J Jaehnig, Jiayi Ji, Wen Jiang, Lizabeth Katsnelson, Karen A Ketchum, Robert J Klein, Jonathan T Lei, Wen-Wei Liang, Yuxing Liao, Caleb M Lindgren, Weiping Ma, Lei Ma, Michael J Maccoss, Fernanda Martins Rodrigues, Wilson Mckerrow, Ngoc Nguyen, Robert Oldroyd, Alexander Pilozzi, Pietro Pugliese, Boris Reva, Paul Rudnick, Kelly V Ruggles, Dmitry Rykunov, Sara R Savage, Michael Schnaubelt, Tobias Schraink, Zhiao Shi, Deepak Singhal, Xiaoyu Song, Erik Storrs, Nadezhda V Terekhanova, Ratna R Thangudu, Mathangi Thiagarajan, Liang-Bo Wang, Joshua M Wang, Ying Wang, Bo Wen, Yige Wu, Matthew A Wyczalkowski, Yi Xin, Lijun Yao, Xinpei Yi, Hui Zhang, Qing Zhang, Maya Zuhl, Gad Getz, Li Ding, Alexey I Nesvizhskii, Pei Wang, Ana I Robles, Bing Zhang, Samuel H Payne Aug 2023

Proteogenomic Data And Resources For Pan-Cancer Analysis, Yize Li, Yongchao Dou, Felipe Da Veiga Leprevost, Yifat Geffen, Anna P Calinawan, François Aguet, Yo Akiyama, Shankara Anand, Chet Birger, Song Cao, Rekha Chaudhary, Padmini Chilappagari, Marcin Cieslik, Antonio Colaprico, Daniel Cui Zhou, Corbin Day, Marcin J Domagalski, Myvizhi Esai Selvan, David Fenyö, Steven M Foltz, Alicia Francis, Tania Gonzalez-Robles, Zeynep H Gümüş, David Heiman, Michael Holck, Runyu Hong, Yingwei Hu, Eric J Jaehnig, Jiayi Ji, Wen Jiang, Lizabeth Katsnelson, Karen A Ketchum, Robert J Klein, Jonathan T Lei, Wen-Wei Liang, Yuxing Liao, Caleb M Lindgren, Weiping Ma, Lei Ma, Michael J Maccoss, Fernanda Martins Rodrigues, Wilson Mckerrow, Ngoc Nguyen, Robert Oldroyd, Alexander Pilozzi, Pietro Pugliese, Boris Reva, Paul Rudnick, Kelly V Ruggles, Dmitry Rykunov, Sara R Savage, Michael Schnaubelt, Tobias Schraink, Zhiao Shi, Deepak Singhal, Xiaoyu Song, Erik Storrs, Nadezhda V Terekhanova, Ratna R Thangudu, Mathangi Thiagarajan, Liang-Bo Wang, Joshua M Wang, Ying Wang, Bo Wen, Yige Wu, Matthew A Wyczalkowski, Yi Xin, Lijun Yao, Xinpei Yi, Hui Zhang, Qing Zhang, Maya Zuhl, Gad Getz, Li Ding, Alexey I Nesvizhskii, Pei Wang, Ana I Robles, Bing Zhang, Samuel H Payne

Faculty, Staff and Students Publications

The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) investigates tumors from a proteogenomic perspective, creating rich multi-omics datasets connecting genomic aberrations to cancer phenotypes. To facilitate pan-cancer investigations, we have generated harmonized genomic, transcriptomic, proteomic, and clinical data for >1000 tumors in 10 cohorts to create a cohesive and powerful dataset for scientific discovery. We outline efforts by the CPTAC pan-cancer working group in data harmonization, data dissemination, and computational resources for aiding biological discoveries. We also discuss challenges for multi-omics data integration and analysis, specifically the unique challenges of working with both nucleotide sequencing and mass spectrometry …


A Multicenter, Controlled Human Infection Study Of Influenza A(H1n1)Pdm09 In Healthy Adults, Justin R Ortiz, David I Bernstein, Daniel F Hoft, Christopher W Woods, Micah T Mcclain, Sharon E Frey, Rebecca C Brady, Christopher Bryant, Ashley Wegel, Robert W Frenck, Emmanuel B Walter, Getahun Abate, Sarah R Williams, Robert L Atmar, Wendy A Keitel, Nadine Rouphael, Mathew J Memoli, Mamodikoe K Makhene, Paul C Roberts, Kathleen M Neuzil Aug 2023

A Multicenter, Controlled Human Infection Study Of Influenza A(H1n1)Pdm09 In Healthy Adults, Justin R Ortiz, David I Bernstein, Daniel F Hoft, Christopher W Woods, Micah T Mcclain, Sharon E Frey, Rebecca C Brady, Christopher Bryant, Ashley Wegel, Robert W Frenck, Emmanuel B Walter, Getahun Abate, Sarah R Williams, Robert L Atmar, Wendy A Keitel, Nadine Rouphael, Mathew J Memoli, Mamodikoe K Makhene, Paul C Roberts, Kathleen M Neuzil

Faculty, Staff and Students Publications

BACKGROUND: We evaluated the associations between baseline influenza virus-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers and subsequent symptomatic influenza virus infection in a controlled human infection study.

METHODS: We inoculated unvaccinated healthy adults aged 18-49 years with an influenza A/California/04/2009/H1N1pdm-like virus (NCT04044352). We collected serial safety labs, serum for HAI and MN, and nasopharyngeal swabs for reverse-transcription polymerase chain reaction (RT-PCR) testing. Analyses used the putative seroprotective titer of ≥40 for HAI and MN. The primary clinical outcome was mild-to-moderate influenza disease (MMID), defined as ≥1 postchallenge positive qualitative RT-PCR test with a qualifying symptom/clinical finding.

RESULTS: Of 76 …


Characterization Of Vascular Morphology Of Neovascular Age-Related Macular Degeneration By Indocyanine Green Angiography, Anish Attarde, Thomas S Riad, Zhao Zhang, Manisha Ahir, Yingbin Fu Aug 2023

Characterization Of Vascular Morphology Of Neovascular Age-Related Macular Degeneration By Indocyanine Green Angiography, Anish Attarde, Thomas S Riad, Zhao Zhang, Manisha Ahir, Yingbin Fu

Faculty, Staff and Students Publications

Age-related macular degeneration (AMD) is a leading cause of blindness among older individuals, and its prevalence is rapidly increasing due to the aging population. Choroidal neovascularization (CNV) or wet AMD, which accounts for 10%-20% of all AMD cases, is responsible for an alarming 80%-90% of AMD-related blindness. Current anti-VEGF therapies show suboptimal responses in approximately 50% of patients. Resistance to anti-VEGF treatment in CNV patients is often associated with arteriolar CNV, while responders tend to have capillary CNV. While fluorescein angiography (FA) is commonly used to assess leakage patterns in wet AMD patients and animal models, it does not provide …


Clinical Outcome Of Tavi Vs Savr In Patients With Severe Aortic Stenosis, Chayakrit Krittanawong, Hafeez Ul Hassan Virk, Joshua Hahn, Zhen Wang, Fu'ad Al-Azzam, Mahboob Alam, Samin Sharma, Hani Jneid Aug 2023

Clinical Outcome Of Tavi Vs Savr In Patients With Severe Aortic Stenosis, Chayakrit Krittanawong, Hafeez Ul Hassan Virk, Joshua Hahn, Zhen Wang, Fu'ad Al-Azzam, Mahboob Alam, Samin Sharma, Hani Jneid

Faculty, Staff and Students Publications

The utilization of transcatheter aortic valve implantation (TAVI) has become the treatment of choice in patients with severe aortic stenosis (AS) with intermediate-to-high surgical risk for surgical aortic valve replacement (SAVR) [...].


Structural Underpinnings Of Mutation Rate Variations In The Human Genome, Zian Liu, Md Abul Hassan Samee Aug 2023

Structural Underpinnings Of Mutation Rate Variations In The Human Genome, Zian Liu, Md Abul Hassan Samee

Faculty, Staff and Students Publications

Single nucleotide mutation rates have critical implications for human evolution and genetic diseases. Importantly, the rates vary substantially across the genome and the principles underlying such variations remain poorly understood. A recent model explained much of this variation by considering higher-order nucleotide interactions in the 7-mer sequence context around mutated nucleotides. This model's success implicates a connection between DNA shape and mutation rates. DNA shape, i.e. structural properties like helical twist and tilt, is known to capture interactions between nucleotides within a local context. Thus, we hypothesized that changes in DNA shape features at and around mutated positions can explain …


Our Search Of Immune Invaders In The Aged Lacrimal Gland, Claudia M Trujillo-Vargas, Cintia S De Paiva Aug 2023

Our Search Of Immune Invaders In The Aged Lacrimal Gland, Claudia M Trujillo-Vargas, Cintia S De Paiva

Faculty, Staff and Students Publications

No abstract provided.


Strategies For The Genomic Analysis Of Admixed Populations, Taotao Tan, Elizabeth G Atkinson Aug 2023

Strategies For The Genomic Analysis Of Admixed Populations, Taotao Tan, Elizabeth G Atkinson

Faculty, Staff and Students Publications

Admixed populations constitute a large portion of global human genetic diversity, yet they are often left out of genomics analyses. This exclusion is problematic, as it leads to disparities in the understanding of the genetic structure and history of diverse cohorts and the performance of genomic medicine across populations. Admixed populations have particular statistical challenges, as they inherit genomic segments from multiple source populations-the primary reason they have historically been excluded from genetic studies. In recent years, however, an increasing number of statistical methods and software tools have been developed to account for and leverage admixture in the context of …


Generation Of A Novel Stra8-Driven Cre Recombinase Strain For Use In Pre-Meiotic Germ Cells In Mice†, Avery A Ahmed, Ernesto Salas, Denise G Lanza, Jason D Heaney, Stephanie A Pangas Aug 2023

Generation Of A Novel Stra8-Driven Cre Recombinase Strain For Use In Pre-Meiotic Germ Cells In Mice†, Avery A Ahmed, Ernesto Salas, Denise G Lanza, Jason D Heaney, Stephanie A Pangas

Faculty, Staff and Students Publications

The development of oocytes occurs over a broad time frame, starting at the earliest stages of embryogenesis and continuing into adulthood. Conditional knockout technologies such as the Cre/loxP recombination system are useful for analyzing oocyte development at specific stages, but not every time frame has appropriate Cre drivers, for instance, during oocyte meiotic initiation through early prophase I in the embryo. Here, we generated a novel knockin mouse line that produces a bicistronic transcript from the endogenous Stra8 locus that includes a "self-cleaving" 2A peptide upstream of cre. This allows for high efficiency cleavage and production of both proteins individually …


Author Correction: Membrane Translocation Process Revealed By In Situ Structures Of Type Ii Secretion System Secretins, Zhili Yu, Yaoming Wu, Muyuan Chen, Tong Huo, Wei Zheng, Steven J Ludtke, Xiaodong Shi, Zhao Wang Aug 2023

Author Correction: Membrane Translocation Process Revealed By In Situ Structures Of Type Ii Secretion System Secretins, Zhili Yu, Yaoming Wu, Muyuan Chen, Tong Huo, Wei Zheng, Steven J Ludtke, Xiaodong Shi, Zhao Wang

Faculty, Staff and Students Publications

No abstract provided.


Dimethyl Sulfoxide Inhibits Bile Acid Synthesis In Healthy Mice But Does Not Protect Mice From Bile-Acid-Induced Liver Damage, Xi Chen, Huiqiao Li, Yu'e Liu, Jing Qi, Bingning Dong, Shixia Huang, Shangang Zhao, Yi Zhu Aug 2023

Dimethyl Sulfoxide Inhibits Bile Acid Synthesis In Healthy Mice But Does Not Protect Mice From Bile-Acid-Induced Liver Damage, Xi Chen, Huiqiao Li, Yu'e Liu, Jing Qi, Bingning Dong, Shixia Huang, Shangang Zhao, Yi Zhu

Faculty, Staff and Students Publications

Bile acids serve a vital function in lipid digestion and absorption; however, their accumulation can precipitate liver damage. In our study, we probed the effects of dimethyl sulfoxide (DMSO) on bile acid synthesis and the ensuing liver damage in mice induced by bile acids. Our findings indicate that DMSO efficaciously curbs bile acid synthesis by inhibiting key enzymes involved in the biosynthetic pathway, both in cultured primary hepatocytes and in vivo. Contrarily, we observed that DMSO treatment did not confer protection against bile-acid-induced liver damage in two distinct mouse models: one induced by a 0.1% DDC diet, leading to bile …


Somatic Cell Structural Variant Mutagenesis And Neurologic Disease, James R Lupski Aug 2023

Somatic Cell Structural Variant Mutagenesis And Neurologic Disease, James R Lupski

Faculty, Staff and Students Publications

Detection of organismal mosaic states for variant alleles faces technical and analytical challenges, as does the association of such variant alleles with susceptibility to neurologic disease. In this issue of Cell Genomics, Maury et al.1 reanalyze genotyping arrays of a schizophrenia cohort providing evidence for the contribution of somatic structural variant mutagenesis and rare variant alleles.


A De Novo Missense Variant In Ezh1 Associated With Developmental Delay Exhibits Functional Deficits In Drosophila Melanogaster, Sharayu V Jangam, Lauren C Briere, Kristy L Jay, Jonathan C Andrews, Melissa A Walker, Lance H Rodan, Frances A High, Undiagnosed Diseases Network, Shinya Yamamoto, David A Sweetser, Michael F Wangler Aug 2023

A De Novo Missense Variant In Ezh1 Associated With Developmental Delay Exhibits Functional Deficits In Drosophila Melanogaster, Sharayu V Jangam, Lauren C Briere, Kristy L Jay, Jonathan C Andrews, Melissa A Walker, Lance H Rodan, Frances A High, Undiagnosed Diseases Network, Shinya Yamamoto, David A Sweetser, Michael F Wangler

Faculty, Staff and Students Publications

EZH1, a polycomb repressive complex-2 component, is involved in a myriad of cellular processes. EZH1 represses transcription of downstream target genes through histone 3 lysine27 (H3K27) trimethylation (H3K27me3). Genetic variants in histone modifiers have been associated with developmental disorders, while EZH1 has not yet been linked to any human disease. However, the paralog EZH2 is associated with Weaver syndrome. Here we report a previously undiagnosed individual with a novel neurodevelopmental phenotype identified to have a de novo missense variant in EZH1 through exome sequencing. The individual presented in infancy with neurodevelopmental delay and hypotonia and was later noted to have …


A Dimensional Approach To Discrepancy In Parenting Styles In Russian Families, Marina A Zhukova, Nan Li, Vitalii Zhukov, Elena L Grigorenko Aug 2023

A Dimensional Approach To Discrepancy In Parenting Styles In Russian Families, Marina A Zhukova, Nan Li, Vitalii Zhukov, Elena L Grigorenko

Faculty, Staff and Students Publications

We investigated the magnitude and direction of differences in parenting styles as they relate to children's mental health problems, as assessed using the CBCL. The sample consisted of 306 families residing in a large industrial city in Russia. We aimed to expand the cross-cultural literature on parenting styles by assessing a sample of Russian families and analyzing how agreement versus disagreement between self-reported and partner-reported parenting styles related to children's mental health problems. The findings suggested that both congruence and incongruence between parenting styles could be associated with children's mental health problems. When parents agreed about high warmth and matched …


Comparison Of Near-Infrared Spectroscopy-Based Cerebral Autoregulatory Indices In Extremely Low Birth Weight Infants, Howard Chao, Sebastian Acosta, Craig Rusin, Christopher Rhee Aug 2023

Comparison Of Near-Infrared Spectroscopy-Based Cerebral Autoregulatory Indices In Extremely Low Birth Weight Infants, Howard Chao, Sebastian Acosta, Craig Rusin, Christopher Rhee

Faculty, Staff and Students Publications

BACKGROUND: Premature infants are born with immature cerebral autoregulation function and are vulnerable to pressure passive cerebral circulation and subsequent brain injury. Measurements derived from near-infrared spectroscopy (NIRS) have enabled continuous assessment of cerebral vasoreactivity. Although NIRS has enabled a growing field of research, the lack of clear standardization in the field remains problematic. A major limitation of current literature is the absence of a comparative analysis of the different methodologies.

OBJECTIVES: To determine the relationship between NIRS-derived continuous indices of cerebral autoregulation in a cohort of extremely low birth weight (ELBW) infants.

METHODS: Premature infants of birth weight 401-1000 …


Loss Of Microrna-30a And Sex-Specific Effects On The Neonatal Hyperoxic Lung Injury, Sandra L Grimm, Samuel Reddick, Xiaoyu Dong, Connor Leek, Amy Xiao Wang, Manuel Cantu Gutierrez, Sean M Hartig, Bhagavatula Moorthy, Cristian Coarfa, Krithika Lingappan Aug 2023

Loss Of Microrna-30a And Sex-Specific Effects On The Neonatal Hyperoxic Lung Injury, Sandra L Grimm, Samuel Reddick, Xiaoyu Dong, Connor Leek, Amy Xiao Wang, Manuel Cantu Gutierrez, Sean M Hartig, Bhagavatula Moorthy, Cristian Coarfa, Krithika Lingappan

Faculty, Staff and Students Publications

BACKGROUND: Bronchopulmonary dysplasia (BPD) is characterized by an arrest in lung development and is a leading cause of morbidity in premature neonates. It has been well documented that BPD disproportionally affects males compared to females, but the molecular mechanisms behind this sex-dependent bias remain unclear. Female mice show greater preservation of alveolarization and angiogenesis when exposed to hyperoxia, accompanied by increased miR-30a expression. In this investigation, we tested the hypothesis that loss of miR-30a would result in male and female mice experiencing similar impairments in alveolarization and angiogenesis under hyperoxic conditions.

METHODS: Wild-type and miR-30a−/− neonatal mice were exposed …


Regeneration And Rejuvenation Of Skin By A Topical Yap Activator, James F Martin Aug 2023

Regeneration And Rejuvenation Of Skin By A Topical Yap Activator, James F Martin

Faculty, Staff and Students Publications

No abstract provided.


Unraveling The Serotonin Saga: From Discovery To Weight Regulation And Beyond – A Comprehensive Scientific Review, Kristine Conde, Shuzheng Fang, Yong Xu Aug 2023

Unraveling The Serotonin Saga: From Discovery To Weight Regulation And Beyond – A Comprehensive Scientific Review, Kristine Conde, Shuzheng Fang, Yong Xu

Faculty, Staff and Students Publications

The prevalence of obesity is rapidly increasing worldwide, while the development of effective obesity therapies lags behind. Although new therapeutic targets to alleviate obesity are identified every day, and drug efficacy is improving, adverse side effects and increased health risks remain serious issues facing the weight-loss industry. Serotonin, also known as 5-HT, has been extensively studied in relation to appetite reduction and weight loss. As a result, dozens of upstream and downstream neural targets of 5-HT have been identified, revealing a multitude of neural circuits involved in mediating the anorexigenic effect of 5-HT. Despite the rise and fall of several …


Implementation And Assessment Of A Laparotomy-Assisted Three-Port Fetoscopic Spina Bifida Repair Program, Corinna Keil, Siegmund Köhler, Benjamin Sass, Maximilian Schulze, Gerald Kalmus, Michael Belfort, Nicolas Schmitt, Daniele Diehl, Alice King, Stefanie Groß, Caitlin D Sutton, Luc Joyeux, Mirjam Wege, Christopher Nimsky, Wiliam E Whitehead, Eberhard Uhl, Thierry A G M Huisman, Bernd A Neubauer, Stefanie Weber, Helmut Hummler, Roland Axt-Fliedner, Ivonne Bedei Aug 2023

Implementation And Assessment Of A Laparotomy-Assisted Three-Port Fetoscopic Spina Bifida Repair Program, Corinna Keil, Siegmund Köhler, Benjamin Sass, Maximilian Schulze, Gerald Kalmus, Michael Belfort, Nicolas Schmitt, Daniele Diehl, Alice King, Stefanie Groß, Caitlin D Sutton, Luc Joyeux, Mirjam Wege, Christopher Nimsky, Wiliam E Whitehead, Eberhard Uhl, Thierry A G M Huisman, Bernd A Neubauer, Stefanie Weber, Helmut Hummler, Roland Axt-Fliedner, Ivonne Bedei

Faculty, Staff and Students Publications

Open spina bifida (OSB) is a congenital, non-lethal malformation with multifactorial etiology. Fetal therapy can be offered under certain conditions to parents after accurate prenatal diagnostic and interdisciplinary counseling. Since the advent of prenatal OSB surgery, various modifications of the original surgical techniques have evolved, including laparotomy-assisted fetoscopic repair. After a two-year preparation time, the team at the University of Giessen and Marburg (UKGM) became the first center to provide a three-port, three-layer fetoscopic repair of OSB via a laparotomy-assisted approach in the German-speaking area. We point out that under the guidance of experienced centers and by intensive multidisciplinary preparation …


Reduced Racial Disparity As A Result Of Survival Improvement In Prostate Cancer, Baoyi Zhang, Jianrong Li, Mabel Tang, Chao Cheng Aug 2023

Reduced Racial Disparity As A Result Of Survival Improvement In Prostate Cancer, Baoyi Zhang, Jianrong Li, Mabel Tang, Chao Cheng

Faculty, Staff and Students Publications

Prostate cancer is a cancer type associated with a high level of racial and socioeconomic disparities as reported by many previous studies. However, the changes in these disparities in the past two decades have not been systematically studied. In this study, we investigated the Surveillance Epidemiology End Results (SEER) data for prostate cancer patients diagnosed during 2004-2018. African Americans and Asians showed significantly better and worse cancer-specific survival (CSS), respectively, compared to non-Hispanic white individuals after adjusting for confounding factors such as age and cancer stage. Importantly, the data indicated that racial disparities fluctuated and reached the highest level during …


The Co-Delivery Of Adenovirus-Based Immune Checkpoint Vaccine Elicits A Potent Anti-Tumor Effect In Renal Carcinoma, Nan Jiang, Yanyan Zheng, Jiage Ding, Jiawei Wang, Fei Zhu, Meng Wang, Navid Sobhani, Praveen Neeli, Gang Wang, Hailong Li, Junnian Zheng, Dafei Chai Aug 2023

The Co-Delivery Of Adenovirus-Based Immune Checkpoint Vaccine Elicits A Potent Anti-Tumor Effect In Renal Carcinoma, Nan Jiang, Yanyan Zheng, Jiage Ding, Jiawei Wang, Fei Zhu, Meng Wang, Navid Sobhani, Praveen Neeli, Gang Wang, Hailong Li, Junnian Zheng, Dafei Chai

Faculty, Staff and Students Publications

Immune-based checkpoint therapy has made significant progress in cancer treatment, but its therapeutic effect is limited. A replication-defective adenovirus (Ad) vaccine encoding tumor antigen carbonic anhydrase IX (CAIX) combined with Ad-encoding immune checkpoint PD-L1 was developed to treat renal carcinoma. Three tumor models, subcutaneous, lung metastasis and orthotopic tumor were established, and Ad vaccines were used to immunize them and evaluate the vaccine's therapeutic effect. Compared to the single Ad vaccine group, the subcutaneous tumor growth was significantly reduced in Ad-CAIX/Ad-PD-L1 combination group. Co-immunization of Ad-CAIX/Ad-PD-L1 enhanced the induction and maturation of CD11c


Dna-Encoded Chemical Libraries Yield Non-Covalent And Non-Peptidic Sars-Cov-2 Main Protease Inhibitors, Ravikumar Jimmidi, Srinivas Chamakuri, Shuo Lu, Melek Nihan Ucisik, Peng-Jen Chen, Kurt M Bohren, Seyed Arad Moghadasi, Leroy Versteeg, Christina Nnabuife, Jian-Yuan Li, Xuan Qin, Ying-Chu Chen, John C Faver, Pranavanand Nyshadham, Kiran L Sharma, Banumathi Sankaran, Allison Judge, Zhifeng Yu, Feng Li, Jeroen Pollet, Reuben S Harris, Martin M Matzuk, Timothy Palzkill, Damian W Young Aug 2023

Dna-Encoded Chemical Libraries Yield Non-Covalent And Non-Peptidic Sars-Cov-2 Main Protease Inhibitors, Ravikumar Jimmidi, Srinivas Chamakuri, Shuo Lu, Melek Nihan Ucisik, Peng-Jen Chen, Kurt M Bohren, Seyed Arad Moghadasi, Leroy Versteeg, Christina Nnabuife, Jian-Yuan Li, Xuan Qin, Ying-Chu Chen, John C Faver, Pranavanand Nyshadham, Kiran L Sharma, Banumathi Sankaran, Allison Judge, Zhifeng Yu, Feng Li, Jeroen Pollet, Reuben S Harris, Martin M Matzuk, Timothy Palzkill, Damian W Young

Faculty, Staff and Students Publications

The development of SARS-CoV-2 main protease (Mpro) inhibitors for the treatment of COVID-19 has mostly benefitted from X-ray structures and preexisting knowledge of inhibitors; however, an efficient method to generate Mpro inhibitors, which circumvents such information would be advantageous. As an alternative approach, we show here that DNA-encoded chemistry technology (DEC-Tec) can be used to discover inhibitors of Mpro. An affinity selection of a 4-billion-membered DNA-encoded chemical library (DECL) using Mpro as bait produces novel non-covalent and non-peptide-based small molecule inhibitors of Mpro with low nanomolar Ki values. Furthermore, these compounds demonstrate efficacy against mutant forms of Mpro that …


Donor-Recipient Specificity And Age-Dependency In Fecal Microbiota Therapy And Probiotic Resolution Of Gastrointestinal Symptoms, Qinglong Wu, Prapaporn Boonma, Shyam Badu, Nazli Yalcinkaya, Sik Yu So, Kevin W Garey, Kent Williams, L Eugene Arnold, Robert J Shulman, Richard Kellermayer, Tor C Savidge Aug 2023

Donor-Recipient Specificity And Age-Dependency In Fecal Microbiota Therapy And Probiotic Resolution Of Gastrointestinal Symptoms, Qinglong Wu, Prapaporn Boonma, Shyam Badu, Nazli Yalcinkaya, Sik Yu So, Kevin W Garey, Kent Williams, L Eugene Arnold, Robert J Shulman, Richard Kellermayer, Tor C Savidge

Faculty, Staff and Students Publications

Fecal microbiota transplantation (FMT) has proven to be an effective treatment for recurrent Clostridioides difficile infection (rCDI) in both adult and pediatric patients. However, as microbiome development is a critical factor in children, it remains unclear whether adult fecal donors can provide age-appropriate functional restoration in pediatric patients. To address this issue, we conducted an integrated systems approach and found that concordant donor strain engraftment, along with metabolite restoration, are associated with FMT outcomes in both adult and pediatric rCDI patients. Although functional restoration after FMT is not strain-specific, specialized metabolic functions are retained in pediatric patients when adult fecal …


An Sms Text Message-Based Type 2 Diabetes Prevention Program For Hispanic Adolescents With Obesity: Qualitative Co-Design Process, Erica Soltero, Callie Lopez, Sandra Mihail, Ayleen Hernandez, Salma M Musaad, Teresia M O'Connor, Debbe Thompson Aug 2023

An Sms Text Message-Based Type 2 Diabetes Prevention Program For Hispanic Adolescents With Obesity: Qualitative Co-Design Process, Erica Soltero, Callie Lopez, Sandra Mihail, Ayleen Hernandez, Salma M Musaad, Teresia M O'Connor, Debbe Thompson

Faculty, Staff and Students Publications

BACKGROUND: SMS text message-based interventions are a promising approach for reaching and engaging high-risk youths, such as Hispanic adolescents with obesity, in health promotion and disease prevention opportunities. This is particularly relevant, given that SMS text messaging is widely accessible and available and that adolescents are frequent texters. Including youths in the development of SMS text message content can lead to more acceptable and relevant messaging; however, few studies include this group as cocollaborators.

OBJECTIVE: This study aimed to use a co-design process to inform the development of SMS text messages that promote healthy physical activity (PA) and sleep behaviors …


Skp2-Mediated Mlkl Degradation Confers Cisplatin-Resistant In Non-Small Cell Lung Cancer Cells, Huiling Zhou, Li Zhou, Qing Guan, Xuyang Hou, Cong Wang, Lijun Liu, Jian Wang, Xinfang Yu, Wei Li, Haidan Liu Aug 2023

Skp2-Mediated Mlkl Degradation Confers Cisplatin-Resistant In Non-Small Cell Lung Cancer Cells, Huiling Zhou, Li Zhou, Qing Guan, Xuyang Hou, Cong Wang, Lijun Liu, Jian Wang, Xinfang Yu, Wei Li, Haidan Liu

Faculty, Staff and Students Publications

Non-small cell lung cancer (NSCLC) is the most prevalent type of cancer and the leading cause of cancer-related death. Chemotherapeutic resistance is a major obstacle in treating NSCLC patients. Here, we discovered that the E3 ligase Skp2 is overexpressed, accompanied by the downregulation of necroptosis-related regulator MLKL in human NSCLC tissues and cell lines. Knockdown of Skp2 inhibited viability, anchorage-independent growth, and in vivo tumor development of NSCLC cells. We also found that the Skp2 protein is negatively correlated with MLKL in NSCLC tissues. Moreover, Skp2 is increased and accompanied by an upregulation of MLKL ubiquitination and degradation in cisplatin-resistant …


Prevention Of Hepatocellular Carcinoma (Hcc) White Paper Of The Texas Collaborative Center For Hepatocellular Cancer (Tech) Multi-Stakeholder Conference, Hashem B El-Serag, John W Ward, Sumeet K Asrani, Amit G Singal, Nicole Rich, Aaron P Thrift, Salil Deshpande, Barbara J Turner, Ahmed O Kaseb, Ariel C Harrison, Brett E Fortune, Fasiha Kanwal Aug 2023

Prevention Of Hepatocellular Carcinoma (Hcc) White Paper Of The Texas Collaborative Center For Hepatocellular Cancer (Tech) Multi-Stakeholder Conference, Hashem B El-Serag, John W Ward, Sumeet K Asrani, Amit G Singal, Nicole Rich, Aaron P Thrift, Salil Deshpande, Barbara J Turner, Ahmed O Kaseb, Ariel C Harrison, Brett E Fortune, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Texas has the highest age-adjusted incidence rate of hepatocellular carcinoma (HCC) in the United States. The Cancer Prevention and Research Institute of Texas has funded the Texas Collaborative Center for Hepatocellular Cancer (TeCH) to facilitate HCC research, education, and advocacy activities with the overall goal of reducing HCC mortality in Texas through coordination, collaboration, and advocacy.

METHODS: On September 17, 2022, TeCH co-sponsored a multi-stakeholder conference on HCC with the Baker Institute Center for Health and Biosciences. This conference was attended by HCC researchers, policy makers, payers, members from pharmaceutical industry and patient advocacy groups in and …


Reduction In Racial And Ethnic Disparity In Survival Following Liver Transplant For Hepatocellular Carcinoma In The Direct-Acting Antiviral Era, Anjiya Shaikh, Karthik Goli, Tzu-Hao Lee, Nicole E Rich, Jihane N Benhammou, Stephanie Keeling, Donghee Kim, Aijaz Ahmed, John Goss, Abbas Rana, Amit G Singal, Fasiha Kanwal, George Cholankeril Aug 2023

Reduction In Racial And Ethnic Disparity In Survival Following Liver Transplant For Hepatocellular Carcinoma In The Direct-Acting Antiviral Era, Anjiya Shaikh, Karthik Goli, Tzu-Hao Lee, Nicole E Rich, Jihane N Benhammou, Stephanie Keeling, Donghee Kim, Aijaz Ahmed, John Goss, Abbas Rana, Amit G Singal, Fasiha Kanwal, George Cholankeril

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Black patients with hepatocellular cancer (HCC), often attributed to hepatitis C virus (HCV) infection, have suboptimal survival following liver transplant (LT). We evaluated the impact of direct-acting antiviral (DAA) availability on racial and ethnic disparities in wait list burden post-LT survival for candidates with HCC.

METHODS: Using the United Network for Organ Sharing registry, we identified patients with HCC who were listed and/or underwent LT from 2009 to 2020. Based on date of LT, patients were categorized into 2 era-based cohorts: the pre-DAA era (LT between 2009 and 2011) and DAA era (LT between 2015 and 2017, …


Interrater Reliability Of Functional Lumen Imaging Probe Panometry And High-Resolution Manometry For The Assessment Of Esophageal Motility Disorders, Joan W Chen, Abraham Khan, Reena V Chokshi, John O Clarke, Ronnie Fass, Jose M Garza, Milli Gupta, C Prakash Gyawali, Anand S Jain, Philip Katz, Vani Konda, Adriana Lazarescu, Kristle L Lynch, Felice Schnoll-Sussman, Stuart J Spechler, Marcelo F Vela, Rena Yadlapati, Jacob M Schauer, Peter J Kahrilas, John E Pandolfino, Dustin A Carlson Aug 2023

Interrater Reliability Of Functional Lumen Imaging Probe Panometry And High-Resolution Manometry For The Assessment Of Esophageal Motility Disorders, Joan W Chen, Abraham Khan, Reena V Chokshi, John O Clarke, Ronnie Fass, Jose M Garza, Milli Gupta, C Prakash Gyawali, Anand S Jain, Philip Katz, Vani Konda, Adriana Lazarescu, Kristle L Lynch, Felice Schnoll-Sussman, Stuart J Spechler, Marcelo F Vela, Rena Yadlapati, Jacob M Schauer, Peter J Kahrilas, John E Pandolfino, Dustin A Carlson

Faculty, Staff and Students Publications

INTRODUCTION: High-resolution manometry (HRM) and functional lumen imaging probe (FLIP) are primary and/or complementary diagnostic tools for the evaluation of esophageal motility. We aimed to assess the interrater agreement and accuracy of HRM and FLIP interpretations.

METHODS: Esophageal motility specialists from multiple institutions completed the interpretation of 40 consecutive HRM and 40 FLIP studies. Interrater agreement was assessed using intraclass correlation coefficient (ICC) for continuous variables and Fleiss' κ statistics for nominal variables. Accuracies of rater interpretation were assessed using the consensus of 3 experienced raters as the reference standard.

RESULTS: Fifteen raters completed the HRM and FLIP studies. An …


Safety And Efficacy Of Underwater Versus Conventional Endoscopic Mucosal Resection For Colorectal Polyps: Systematic Review And Meta-Analysis Of Rcts, Saurabh Chandan, Jay Bapaye, Shahab R Khan, Babu P Mohan, Daryl Ramai, Dushyant S Dahiya, Mohammad Bilal, Peter V Draganov, Mohamed O Othman, Joaquin Rodriguez Sánchez, Gursimran S Kochhar Aug 2023

Safety And Efficacy Of Underwater Versus Conventional Endoscopic Mucosal Resection For Colorectal Polyps: Systematic Review And Meta-Analysis Of Rcts, Saurabh Chandan, Jay Bapaye, Shahab R Khan, Babu P Mohan, Daryl Ramai, Dushyant S Dahiya, Mohammad Bilal, Peter V Draganov, Mohamed O Othman, Joaquin Rodriguez Sánchez, Gursimran S Kochhar

Faculty, Staff and Students Publications

Background and study aims Conventional endoscopic mucosal resection (C-EMR) is limited by low en-bloc resection rates, especially for large (> 20 mm) lesions. Underwater EMR (U-EMR) has emerged as an alternative for colorectal polyps and is being shown to improve en-bloc resection rates. We conducted a systematic review and meta-analysis comparing the two techniques.

Methods Multiple databases were searched through November 2022 for randomized controlled trials (RCTs) comparing outcomes of U-EMR and C-EMR for colorectal polyps. Meta-analysis was performed to determine pooled proportions and relative risks (RRs) of R0 and en-bloc resection, polyp recurrence, resection time, and adverse events.

Results …


Androgen-Regulated Stromal Complement Component 7 (C7) Suppresses Prostate Cancer Growth, Zhicheng Zhou, Deyong Jia, Ohjoon Kwon, Shan Li, Huiyun Sun, Martine P Roudier, Daniel W Lin, Lawrence True, Colm Morrissey, Chad J Creighton, John K Lee, Li Xin Aug 2023

Androgen-Regulated Stromal Complement Component 7 (C7) Suppresses Prostate Cancer Growth, Zhicheng Zhou, Deyong Jia, Ohjoon Kwon, Shan Li, Huiyun Sun, Martine P Roudier, Daniel W Lin, Lawrence True, Colm Morrissey, Chad J Creighton, John K Lee, Li Xin

Faculty, Staff and Students Publications

The complement system is a major component of the innate immune system that works through the cytolytic effect of the membrane attack complex (MAC). Complement component 7 (C7) is essential for MAC assembly and its precisely regulated expression level is crucial for the cytolytic activity of MAC. We show that C7 is specifically expressed by the stromal cells in both mouse and human prostates. The expression level of C7 inversely correlates with clinical outcomes in prostate cancer. C7 is positively regulated by androgen signaling in the mouse prostate stromal cells. The androgen receptor directly transcriptionally regulates the mouse and human …


Contingency Management With Stepped Care For Unhealthy Alcohol Use Among Individuals With Hiv: Protocol For A Randomized Controlled Trial, E Jennifer Edelman, James Dziura, Yanhong Deng, Dominick Dephilippis, Lisa M Fucito, Tekeda Ferguson, Roger Bedimo, Sheldon Brown, Vincent C Marconi, Matthew Bidwell Goetz, Maria C Rodriguez-Barradas, Michael S Simberkoff, Patricia E Molina, Amy C Weintrob, Stephen A Maisto, Manuel Paris, Amy C Justice, Kendall J Bryant, David A Fiellin Aug 2023

Contingency Management With Stepped Care For Unhealthy Alcohol Use Among Individuals With Hiv: Protocol For A Randomized Controlled Trial, E Jennifer Edelman, James Dziura, Yanhong Deng, Dominick Dephilippis, Lisa M Fucito, Tekeda Ferguson, Roger Bedimo, Sheldon Brown, Vincent C Marconi, Matthew Bidwell Goetz, Maria C Rodriguez-Barradas, Michael S Simberkoff, Patricia E Molina, Amy C Weintrob, Stephen A Maisto, Manuel Paris, Amy C Justice, Kendall J Bryant, David A Fiellin

Faculty, Staff and Students Publications

BACKGROUND: Although unhealthy alcohol use is associated with increased morbidity and mortality among people with HIV (PWH), many are ambivalent about engaging in treatment and experience variable responses to treatment. We describe the rationale, aims, and study design for the Financial Incentives, Randomization, with Stepped Treatment (FIRST) Trial, a multi-site randomized controlled efficacy trial.

METHODS: PWH in care recruited from clinics across the United States who reported unhealthy alcohol use, had a phosphatidylethanol (PEth) >20 ng/mL, and were not engaged in formal alcohol treatment were randomized to integrated contingency management with stepped care versus treatment as usual. The intervention involved …