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Txnrd1 Drives The Innate Immune Response In Senescent Cells With Implications For Age-Associated Inflammation, Xue Hao, Bo Zhao, Martina Towers, Liping Liao, Edgar Luzete Monteiro, Xin Xu, Christina Freeman, Hongzhuang Peng, Hsin-Yao Tang, Aaron Havas, Andrew V Kossenkov, Shelley L Berger, Peter D Adams, David W Speicher, David Schultz, Ronen Marmorstein, Kenneth S Zaret, Rugang Zhang Feb 2024

Txnrd1 Drives The Innate Immune Response In Senescent Cells With Implications For Age-Associated Inflammation, Xue Hao, Bo Zhao, Martina Towers, Liping Liao, Edgar Luzete Monteiro, Xin Xu, Christina Freeman, Hongzhuang Peng, Hsin-Yao Tang, Aaron Havas, Andrew V Kossenkov, Shelley L Berger, Peter D Adams, David W Speicher, David Schultz, Ronen Marmorstein, Kenneth S Zaret, Rugang Zhang

Faculty, Staff and Student Publications

Sterile inflammation, also known as 'inflammaging', is a hallmark of tissue aging. Cellular senescence contributes to tissue aging, in part, through the secretion of proinflammatory factors collectively known as the senescence-associated secretory phenotype (SASP). The genetic variability of thioredoxin reductase 1 (TXNRD1) is associated with aging and age-associated phenotypes such as late-life survival, activity of daily living and physical performance in old age. TXNRD1's role in regulating tissue aging has been attributed to its enzymatic role in cellular redox regulation. Here, we show that TXNRD1 drives the SASP and inflammaging through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) …


Enhancing Anti-Aml Activity Of Venetoclax By Isoflavone Me-344 Through Suppression Of Oxphos And/Or Purine Biosynthesis In Vitro, Katie H Hurrish, Yongwei Su, Shraddha Patel, Cassandra L Ramage, Jianlei Zhao, Brianna R Temby, Jenna L Carter, Holly Edwards, Steven A Buck, Sandra E Wiley, Maik Hüttemann, Lisa Polin, Juiwanna Kushner, Sijana H Dzinic, Kathryn White, Xun Bao, Jing Li, Jay Yang, Julie Boerner, Zhanjun Hou, Gheath Al-Atrash, Sergej N Konoplev, Jonathan Busquets, Stefano Tiziani, Larry H Matherly, Jeffrey W Taub, Marina Konopleva, Yubin Ge, Natalia Baran Feb 2024

Enhancing Anti-Aml Activity Of Venetoclax By Isoflavone Me-344 Through Suppression Of Oxphos And/Or Purine Biosynthesis In Vitro, Katie H Hurrish, Yongwei Su, Shraddha Patel, Cassandra L Ramage, Jianlei Zhao, Brianna R Temby, Jenna L Carter, Holly Edwards, Steven A Buck, Sandra E Wiley, Maik Hüttemann, Lisa Polin, Juiwanna Kushner, Sijana H Dzinic, Kathryn White, Xun Bao, Jing Li, Jay Yang, Julie Boerner, Zhanjun Hou, Gheath Al-Atrash, Sergej N Konoplev, Jonathan Busquets, Stefano Tiziani, Larry H Matherly, Jeffrey W Taub, Marina Konopleva, Yubin Ge, Natalia Baran

Faculty, Staff and Student Publications

Venetoclax (VEN), in combination with low dose cytarabine (AraC) or a hypomethylating agent, is FDA approved to treat acute myeloid leukemia (AML) in patients who are over the age of 75 or cannot tolerate standard chemotherapy. Despite high response rates to these therapies, most patients succumb to the disease due to relapse and/or drug resistance, providing an unmet clinical need for novel therapies to improve AML patient survival. ME-344 is a potent isoflavone with demonstrated inhibitory activity toward oxidative phosphorylation (OXPHOS) and clinical activity in solid tumors. Given that OXPHOS inhibition enhances VEN antileukemic activity against AML, we hypothesized that …


Ethnic Minorities And Family Health History: An Autoethnography Of Guyanese Americans And Kidney Disease, Dhaneesha R. Bahadur Feb 2024

Ethnic Minorities And Family Health History: An Autoethnography Of Guyanese Americans And Kidney Disease, Dhaneesha R. Bahadur

Dissertations, Theses, and Capstone Projects

Exploring family health histories (FHHs) has emerged in recent years as an inexpensive genomic tool in public health. Families and clinicians can also use them to uncover family histories and experiences, which could inform better lifestyle choices to prevent or delay the onset of diseases. Exploring family health histories focuses on an individual’s genetic makeup and considers differences in lifestyle and environment. Despite national campaigns, it is an underutilized tool that could lead to engagement in effective strategies and better health outcomes. One important and serious condition that families should be more aware of is chronic kidney disease (CKD). One …


Metabolism, Fibrosis, And Apoptosis: The Effect Of Lipids And Their Derivatives On Keloid Formation, Chen-Yu Li, Ru-Xin Xie, Shi-Wei Zhang, Jiao Yun, Ai Zhong, Ying Cen, Jun-Jie Chen Feb 2024

Metabolism, Fibrosis, And Apoptosis: The Effect Of Lipids And Their Derivatives On Keloid Formation, Chen-Yu Li, Ru-Xin Xie, Shi-Wei Zhang, Jiao Yun, Ai Zhong, Ying Cen, Jun-Jie Chen

Faculty, Staff and Student Publications

Keloids, pathological scars resulting from skin trauma, have traditionally posed significant clinical management challenges due to their persistence and high recurrence rates. Our research elucidates the pivotal roles of lipids and their derivatives in keloid development, driven by underlying mechanisms of abnormal cell proliferation, apoptosis, and extracellular matrix deposition. Key findings suggest that abnormalities in arachidonic acid (AA) synthesis and non-essential fatty acid synthesis are integral to keloid formation. Further, a complex interplay exists between lipid derivatives, notably butyric acid (BA), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and the regulation of hyperfibrosis. Additionally, combinations of docosahexaenoic acid (DHA) with BA …


Predicting And Identifying Factors Associated With Undernutrition Among Children Under Five Years In Ghana Using Machine Learning Algorithms, Eric Komla Anku, Henry Ofori Duah Feb 2024

Predicting And Identifying Factors Associated With Undernutrition Among Children Under Five Years In Ghana Using Machine Learning Algorithms, Eric Komla Anku, Henry Ofori Duah

College of Nursing Faculty Research and Publications

Background Undernutrition among children under the age of five is a major public health concern, especially in developing countries. This study aimed to use machine learning (ML) algorithms to predict undernutrition and identify its associated factors. Methods Secondary data analysis of the 2017 Multiple Indicator Cluster Survey (MICS) was performed using R and Python. The main outcomes of interest were undernutrition (stunting: height-for-age (HAZ) < -2 SD; wasting: weight-for-height (WHZ) < -2 SD; and underweight: weight-for-age (WAZ) < -2 SD). Seven ML algorithms were trained and tested: linear discriminant analysis (LDA), logistic model, support vector machine (SVM), random forest (RF), least absolute shrinkage and selection operator (LASSO), ridge regression, and extreme gradient boosting (XGBoost). The ML models were evaluated using the accuracy, confusion matrix, and area under the curve (AUC) receiver operating characteristics (ROC). Results In total, 8564 children were included in the final analysis. The average age of the children was 926 days, and the majority were females. The weighted prevalence rates of stunting, wasting, and underweight were 17%, 7%, and 12%, respectively. The accuracies of all the ML models for wasting were (LDA: 84%; Logistic: 95%; SVM: 92%; RF: 94%; LASSO: 96%; Ridge: 84%, XGBoost: 98%), stunting (LDA: 86%; Logistic: 86%; SVM: 98%; RF: 88%; LASSO: 86%; Ridge: 86%, XGBoost: 98%), and for underweight were (LDA: 90%; Logistic: 92%; SVM: 98%; RF: 89%; LASSO: 92%; Ridge: 88%, XGBoost: 98%). The AUC values of the wasting models were (LDA: 99%; Logistic: 100%; SVM: 72%; RF: 94%; LASSO: 99%; Ridge: 59%, XGBoost: 100%), for stunting were (LDA: 89%; Logistic: 90%; SVM: 100%; RF: 92%; LASSO: 90%; Ridge: 89%, XGBoost: 100%), and for underweight were (LDA: 95%; Logistic: 96%; SVM: 100%; RF: 94%; LASSO: 96%; Ridge: 82%, XGBoost: 82%). Age, weight, length/height, sex, region of residence and ethnicity were important predictors of wasting, stunting and underweight. Conclusion The XGBoost model was the best model for predicting wasting, stunting, and underweight. The findings showed that different ML algorithms could be useful for predicting undernutrition and identifying important predictors for targeted interventions among children under five years in Ghana.


The Association Of Hiv-Related Stigma And Psychosocial Factors And Hiv Treatment Outcomes Among People Living With Hiv In The Volta Region Of Ghana: A Mixed-Methods Study, Jerry John Nutor, Akua O. Gyamerah, Henry Ofori Duah, David Ayangba Asakitogum, Rachel G.A. Thompson, Robert Kaba Alhassan, Alison Hamilton Feb 2024

The Association Of Hiv-Related Stigma And Psychosocial Factors And Hiv Treatment Outcomes Among People Living With Hiv In The Volta Region Of Ghana: A Mixed-Methods Study, Jerry John Nutor, Akua O. Gyamerah, Henry Ofori Duah, David Ayangba Asakitogum, Rachel G.A. Thompson, Robert Kaba Alhassan, Alison Hamilton

College of Nursing Faculty Research and Publications

Stigma and discrimination have been identified as significant barriers to HIV treatment among people living with HIV (PLWH). HIV stigma affects decision to seek HIV testing and early treatment. Evidence shows that HIV stigma undermines antiretroviral therapy (ART) adherence by affecting the psychological process such as adjusting and coping with social support. In Ghana, stigma toward PLWH occurs in many ways including rejection by their communities and family members, ostracism, and refusal to engage in social interactions such as eating, sharing a bed, or shaking hands. Therefore. we examined PLWH’s experiences with different forms of HIV-related stigma and the impact …


The Divided Self: Internal Conflict In Literature, Philosophy, Psychology, And Neuroscience, Yulia Greyman Feb 2024

The Divided Self: Internal Conflict In Literature, Philosophy, Psychology, And Neuroscience, Yulia Greyman

Dissertations, Theses, and Capstone Projects

This thematic project examines the notion of self-division, particularly in terms of the conflict between cognition and metacognition, across the fields of philosophy, psychology, and, most recently, the cognitive and neurosciences. The project offers a historic overview of models of self-division, as well as analyses of the various problems presented in theoretical models to date. This work explores how self-division has been depicted in the literary works of Edgar Allan Poe, Don DeLillo, and Mary Shelley. It examines the ways in which artistic renderings alternately assimilate, resist, and/or critique dominant philosophical, psychological, and scientific discourses about the self and its …


Clostridium Butyricum And Carbohydrate Active Enzymes Contribute To The Reduced Fat Deposition In Pigs, Lingyan Ma, Shiyu Tao, Tongxing Song, Wentao Lyu, Ying Li, Wen Wang, Qicheng Shen, Yan Ni, Jiang Zhu, Jiangchao Zhao, Hua Yang, Yingping Xiao Feb 2024

Clostridium Butyricum And Carbohydrate Active Enzymes Contribute To The Reduced Fat Deposition In Pigs, Lingyan Ma, Shiyu Tao, Tongxing Song, Wentao Lyu, Ying Li, Wen Wang, Qicheng Shen, Yan Ni, Jiang Zhu, Jiangchao Zhao, Hua Yang, Yingping Xiao

Animal Science Faculty Publications and Presentations

Pig gastrointestinal tracts harbor a heterogeneous and dynamic ecosystem populated with trillions of microbes, enhancing the ability of the host to harvest energy from dietary carbohydrates and contributing to host adipogenesis and fatness. However, the microbial community structure and related mechanisms responsible for the differences between the fatty phenotypes and the lean phenotypes of the pigs remained to be comprehensively elucidated. Herein, we first found significant differences in microbial composition and potential functional capacity among different gut locations in Jinhua pigs with distinct fatness phenotypes. Second, we identified that Jinhua pigs with lower fatness exhibited higher levels of short-chain fatty …


Application Of The Adverse Childhood Experiences Framework To The Nicu, Kathryn J. Malin, Dorothy Vittner, Darilek Umber, Kelly Mcglothen-Bell, Allison Crawford, Rebecca Koerner, Britt Frisk Pados, Diana Cartegena, Jacqueline M. Mcgrath, Ashlee J. Vance Feb 2024

Application Of The Adverse Childhood Experiences Framework To The Nicu, Kathryn J. Malin, Dorothy Vittner, Darilek Umber, Kelly Mcglothen-Bell, Allison Crawford, Rebecca Koerner, Britt Frisk Pados, Diana Cartegena, Jacqueline M. Mcgrath, Ashlee J. Vance

College of Nursing Faculty Research and Publications

Background:

Infants and families requiring neonatal intensive care unit (NICU) care often experience significant stress and trauma during the earliest period of the infant's life, leading to increased risks for poorer infant and family outcomes. There is a need for frameworks to guide clinical care and research that account for the complex interactions of generational stress, pain, toxic stress, parental separation, and lifelong health and developmental outcomes for infants and families.

Purpose:

Apply the Adverse Childhood Experiences (ACEs) framework in the context of the NICU as a usable structure to guide clinical practice and research focused on infant neurodevelopment outcomes …


Enhancing Product Design Through Ai-Driven Sentiment Analysis Of Amazon Reviews Using Bert, Mahammad Khalid Shaik Vadla, Mahima Agumbe Suresh, Vimal K. Viswanathan Feb 2024

Enhancing Product Design Through Ai-Driven Sentiment Analysis Of Amazon Reviews Using Bert, Mahammad Khalid Shaik Vadla, Mahima Agumbe Suresh, Vimal K. Viswanathan

Faculty Research, Scholarly, and Creative Activity

Understanding customer emotions and preferences is paramount for success in the dynamic product design landscape. This paper presents a study to develop a prediction pipeline to detect the aspect and perform sentiment analysis on review data. The pre-trained Bidirectional Encoder Representation from Transformers (BERT) model and the Text-to-Text Transfer Transformer (T5) are deployed to predict customer emotions. These models were trained on synthetically generated and manually labeled datasets to detect the specific features from review data, then sentiment analysis was performed to classify the data into positive, negative, and neutral reviews concerning their aspects. This research focused on eco-friendly products …


The Silent Majority: Pico- And Nanoplankton As Ecosystem Health Indicators For Marine Policy, Abigail Mcquatters-Gollop, Rowena F. Stern, Angus Atkinson, Mike Best, Eileen Bresnan, Veronique Creach, Michelle Devlin, Matthew Holland, Clare Ostle, Katrin Schmidt, Lawrence Sheppard, Glen Tarran, E. Malcolm S. Woodward, Paul Tett Feb 2024

The Silent Majority: Pico- And Nanoplankton As Ecosystem Health Indicators For Marine Policy, Abigail Mcquatters-Gollop, Rowena F. Stern, Angus Atkinson, Mike Best, Eileen Bresnan, Veronique Creach, Michelle Devlin, Matthew Holland, Clare Ostle, Katrin Schmidt, Lawrence Sheppard, Glen Tarran, E. Malcolm S. Woodward, Paul Tett

School of Biological and Marine Sciences

A healthy marine ecosystem is a fully functioning system, able to supply ecosystem services whilst still maintaining resilience to human-induced environmental change. Monitoring and managing the health of resilient marine ecosystems requires indicators that can assess their biodiversity state and food web functioning. Plankton are crucial components of pelagic habitats, occupying the base of the pelagic food web. Larger plankton have long been used to monitor ecosystem productivity and biodiversity due to their identification via traditional light microscopy. In contrast, the regular monitoring of pico- and nanoplankton (<20 µm; hereafter called “tiny plankton”) only started with the development of flow cytometry techniques, which has limited their inclusion as ecosystem health indicators. Four UK plankton surveys have sampled and identified these tiny plankton for up to 14 years, providing an opportunity to test their suitability as indicators of ecosystem state. We investigated six groups of tiny plankton, including heterotrophic nanoeukaryotes, photosynthetic nanoeukaryotes, photosynthetic picoeukaryotes, and Synechococcus cyanobacteria, and two groups of heterotrophic bacteria. Flow cytometry and light microscopy data from an inshore Western English Channel station revealed that 99.98 % of plankton abundance and 71 % of plankton biomass was derived from tiny plankton cells too small to be quantified accurately under a light microscope and thus not adequately considered in assessments of pelagic habitats. Different UK marine and coastal regions showed consistency in peak abundances of these tiny plankton. We used a novel wavelet coherence method to identify time-based relationships between tiny plankton and environmental variables linked to human pressures. Relationships were found between nitrogenous nutrients and all tiny plankton groups, most commonly at sub-annual to annual time scales. Photosynthetic picoeukaryotes, heterotrophic nanoeukaryotes, and HNA-bacteria were associated with high sea surface temperatures. Given the here established relationship between tiny plankton and environmental variables, and their importance in the full plankton assemblage, we recommend that, alongside existing microplankton lifeforms, tiny plankton groups can be used as plankton lifeforms, either individually or in combination, to inform biodiversity indicators that meet policy obligations under the EU Marine Strategy Framework Directive (MSFD), (Oslo-Paris Convention) OSPAR strategies, and the UK Marine Strategy.


Host Gastric Corpus Microenvironment Facilitates Ascaris Suum Larval Hatching And Infection In A Murine Model, Yifan Wu, Grace Adeniyi-Ipadeola, Mahliyah Adkins-Threats, Matthew Seasock, Charlie Suarez-Reyes, Ricardo Fujiwara, Maria Elena Bottazzi, Lizhen Song, Jason C Mills, Jill E Weatherhead Feb 2024

Host Gastric Corpus Microenvironment Facilitates Ascaris Suum Larval Hatching And Infection In A Murine Model, Yifan Wu, Grace Adeniyi-Ipadeola, Mahliyah Adkins-Threats, Matthew Seasock, Charlie Suarez-Reyes, Ricardo Fujiwara, Maria Elena Bottazzi, Lizhen Song, Jason C Mills, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected with Ascaris spp. via oral ingestion of eggs. It has long been assumed that Ascaris egg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, we show that A. suum larvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase; Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric …


Genetic Architecture And Biology Of Youth-Onset Type 2 Diabetes, Soo Heon Kwak, Shylaja Srinivasan, Ling Chen, Jennifer Todd, Josep M Mercader, Elizabeth T Jensen, Jasmin Divers, Amy K Mottl, Catherine Pihoker, Rachelle G Gandica, Lori M Laffel, Elvira Isganaitis, Morey W Haymond, Lynne L Levitsky, Toni I Pollin, Jose C Florez, Jason Flannick, Progress In Diabetes Genetics In Youth (Prodigy) Consortium Feb 2024

Genetic Architecture And Biology Of Youth-Onset Type 2 Diabetes, Soo Heon Kwak, Shylaja Srinivasan, Ling Chen, Jennifer Todd, Josep M Mercader, Elizabeth T Jensen, Jasmin Divers, Amy K Mottl, Catherine Pihoker, Rachelle G Gandica, Lori M Laffel, Elvira Isganaitis, Morey W Haymond, Lynne L Levitsky, Toni I Pollin, Jose C Florez, Jason Flannick, Progress In Diabetes Genetics In Youth (Prodigy) Consortium

Faculty, Staff and Students Publications

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily1, producing a growing public health concern1 that disproportionately affects minority groups2. The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear3. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant ( …


Leptin Reduction As A Required Component For Weight Loss, Shangang Zhao, Na Li, Wei Xiong, Guannan Li, Sijia He, Zhuzhen Zhang, Qingzhang Zhu, Nisi Jiang, Christian Ikejiofor, Yi Zhu, May-Yun Wang, Xianlin Han, Ningyang Zhang, Carolina Solis-Herrera, Christine Kusminski, Zhiqiang An, Joel K Elmquist, Philipp E Scherer Feb 2024

Leptin Reduction As A Required Component For Weight Loss, Shangang Zhao, Na Li, Wei Xiong, Guannan Li, Sijia He, Zhuzhen Zhang, Qingzhang Zhu, Nisi Jiang, Christian Ikejiofor, Yi Zhu, May-Yun Wang, Xianlin Han, Ningyang Zhang, Carolina Solis-Herrera, Christine Kusminski, Zhiqiang An, Joel K Elmquist, Philipp E Scherer

Faculty, Staff and Students Publications

Partial leptin reduction can induce significant weight loss, while weight loss contributes to partial leptin reduction. The cause-and-effect relationship between leptin reduction and weight loss remains to be further elucidated. Here, we show that FGF21 and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide rapidly induced a reduction in leptin. This leptin reduction contributed to the beneficial effects of GLP-1R agonism in metabolic health, as transgenically maintaining leptin levels during treatment partially curtailed the beneficial effects seen with these agonists. Moreover, a higher degree of leptin reduction during treatment, induced by including a leptin neutralizing antibody with either FGF21 or …


Number Of Children In The Household Influences Respiratory Morbidities In Children With Bronchopulmonary Dysplasia In The Outpatient Setting, Joseph M Collaco, Katharine R Tsukahara, Michael C Tracy, Catherine A Sheils, Jessica L Rice, Lawrence M Rhein, Antonia P Popova, Leif Nelin, Audrey N Miller, Winston M Manimtim, Jonathan C Levin, Khanh Lai, Jacob A Kaslow, Lystra P Hayden, Manvi Bansal, Eric D Austin, Brianna Aoyama, Gangaram Akangire, Amit Agarwal, Natalie Villafranco, Sharon A Mcgrath-Morrow Feb 2024

Number Of Children In The Household Influences Respiratory Morbidities In Children With Bronchopulmonary Dysplasia In The Outpatient Setting, Joseph M Collaco, Katharine R Tsukahara, Michael C Tracy, Catherine A Sheils, Jessica L Rice, Lawrence M Rhein, Antonia P Popova, Leif Nelin, Audrey N Miller, Winston M Manimtim, Jonathan C Levin, Khanh Lai, Jacob A Kaslow, Lystra P Hayden, Manvi Bansal, Eric D Austin, Brianna Aoyama, Gangaram Akangire, Amit Agarwal, Natalie Villafranco, Sharon A Mcgrath-Morrow

Faculty, Staff and Students Publications

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with outpatient morbidities, including respiratory exacerbations. Daycare attendance is associated with increased rates of acute and chronic morbidities in children with BPD. We sought to determine if additional children in the household conferred similar risks for children with BPD.

METHODS: The number of children in the household and clinical outcomes were obtained via validated instruments for 933 subjects recruited from 13 BPD specialty clinics in the United States. Clustered logistic regression models were used to test for associations.

RESULTS: The mean gestational age of the study population was 26.5 …


Pulsatile Leucine Administration During Continuous Enteral Feeding Enhances Skeletal Muscle Mechanistic Target Of Rapamycin Complex 1 Signaling And Protein Synthesis In A Preterm Piglet Model, Marko Rudar, Agus Suryawan, Hanh V Nguyen, Shaji K Chacko, Caitlin Vonderohe, Barbara Stoll, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis Feb 2024

Pulsatile Leucine Administration During Continuous Enteral Feeding Enhances Skeletal Muscle Mechanistic Target Of Rapamycin Complex 1 Signaling And Protein Synthesis In A Preterm Piglet Model, Marko Rudar, Agus Suryawan, Hanh V Nguyen, Shaji K Chacko, Caitlin Vonderohe, Barbara Stoll, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

BACKGROUND: Continuous feeding does not elicit an optimal anabolic response in skeletal muscle but is required for some preterm infants. We reported previously that intermittent intravenous pulses of leucine (Leu; 800 μmol Leu·kg–1·h–1 every 4 h) to continuously fed pigs born at term promoted mechanistic target of rapamycin complex 1 (mTORC1) activation and protein synthesis in skeletal muscle.

OBJECTIVES: The aim was to determine the extent to which intravenous Leu pulses activate mTORC1 and enhance protein synthesis in the skeletal muscle of continuously fed pigs born preterm.

METHODS: Pigs delivered 10 d preterm was advanced to full oral feeding >4 …


Nonchromosomal Birth Defects And Risk Of Childhood Acute Leukemia: An Assessment In 15 000 Leukemia Cases And 46 000 Controls From The Childhood Cancer And Leukemia International Consortium, Philip J Lupo, Tiffany M Chambers, Beth A Mueller, Jacqueline Clavel, John D Dockerty, David R Doody, Friederike Erdmann, Sameera Ezzat, Tommaso Filippini, Johnni Hansen, Julia E Heck, Claire Infante-Rivard, Alice Y Kang, Corrado Magnani, Carlotta Malagoli, Erin L Marcotte, Catherine Metayer, Helen D Bailey, Ana M Mora, Evangelia Ntzani, Eleni Th Petridou, Maria S Pombo-De-Oliveira, Wafaa M Rashed, Eve Roman, Joachim Schüz, Catharina Wesseling, Logan G Spector, Michael E Scheurer Feb 2024

Nonchromosomal Birth Defects And Risk Of Childhood Acute Leukemia: An Assessment In 15 000 Leukemia Cases And 46 000 Controls From The Childhood Cancer And Leukemia International Consortium, Philip J Lupo, Tiffany M Chambers, Beth A Mueller, Jacqueline Clavel, John D Dockerty, David R Doody, Friederike Erdmann, Sameera Ezzat, Tommaso Filippini, Johnni Hansen, Julia E Heck, Claire Infante-Rivard, Alice Y Kang, Corrado Magnani, Carlotta Malagoli, Erin L Marcotte, Catherine Metayer, Helen D Bailey, Ana M Mora, Evangelia Ntzani, Eleni Th Petridou, Maria S Pombo-De-Oliveira, Wafaa M Rashed, Eve Roman, Joachim Schüz, Catharina Wesseling, Logan G Spector, Michael E Scheurer

Faculty, Staff and Students Publications

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia …


The Psychosocial Beliefs, Experiences And Expectations Of Children Living With Obesity, Lisa Newson, Nicola Sides, Amineh Rashidi Feb 2024

The Psychosocial Beliefs, Experiences And Expectations Of Children Living With Obesity, Lisa Newson, Nicola Sides, Amineh Rashidi

Research outputs 2022 to 2026

Background: Childhood obesity has been shown to impair psychological health. However, psychological factors are often overlooked in both research evaluations and treatment interventions, and children's perspectives on managing obesity are underexplored. Neglecting psychosocial factors might undermine interventions. This research explored the psychological beliefs, expectations and experiences of children living with obesity (range 7–13) and attending a weight management programme (WMP). Methods: Thirty-four participants (19 females, 15 males, average age 9.5 years) completed a semistructured interview. Recorded interviews were transcribed verbatim and analysed using thematic analysis. Results: Four overarching themes were developed: (1) defining health and self-recognition; (2) external influence; feedback, …


Dropout From Exercise Trials Among Cancer Survivors—An Individual Patient Data Meta-Analysis From The Polaris Study, Benedikte Western, Andreas Ivarsson, Ingvild Vistad, Ingrid Demmelmaier, Neil K. Aaronson, Gillian Radcliffe, Marc Van Beurden, Martin Bohus, Kerry S. Courneya, Amanda J. Daley, Daniel A. Galvão, Rachel Garrod, Martine M. Goedendorp, Kathleen A. Griffith, Wim H. Van Harten, Sandi C. Hayes, Fernando Herrero-Roman, Anouk E. Hiensch, Melinda L. Irwin, Erica James, Marlou-Floor Kenkhuis, Marie J. Kersten, Hans Knoop, Alejandro Lucia, Anne M. May, Alex Mcconnachie, Willem Van Mechelen, Nanette Mutrie, Robert U. Newton, Frans Nollet, Hester S. Oldenburg, Ron Plotnikoff, Martina E. Schmidt, Katie H. Schmitz, Karl-Heinz Schulz, Camille E. Short, Gabe S. Sonke, Karen Steindorf, Martijn M. Stuiver, Dennis R. Taaffe, Lene Thorsen, Miranda J. Velthuis, Jennifer Wenzel, Kerri M. Winters-Stone, Joachim Wiskemann, Sveinung Berntsen, Laurien M. Buffart Feb 2024

Dropout From Exercise Trials Among Cancer Survivors—An Individual Patient Data Meta-Analysis From The Polaris Study, Benedikte Western, Andreas Ivarsson, Ingvild Vistad, Ingrid Demmelmaier, Neil K. Aaronson, Gillian Radcliffe, Marc Van Beurden, Martin Bohus, Kerry S. Courneya, Amanda J. Daley, Daniel A. Galvão, Rachel Garrod, Martine M. Goedendorp, Kathleen A. Griffith, Wim H. Van Harten, Sandi C. Hayes, Fernando Herrero-Roman, Anouk E. Hiensch, Melinda L. Irwin, Erica James, Marlou-Floor Kenkhuis, Marie J. Kersten, Hans Knoop, Alejandro Lucia, Anne M. May, Alex Mcconnachie, Willem Van Mechelen, Nanette Mutrie, Robert U. Newton, Frans Nollet, Hester S. Oldenburg, Ron Plotnikoff, Martina E. Schmidt, Katie H. Schmitz, Karl-Heinz Schulz, Camille E. Short, Gabe S. Sonke, Karen Steindorf, Martijn M. Stuiver, Dennis R. Taaffe, Lene Thorsen, Miranda J. Velthuis, Jennifer Wenzel, Kerri M. Winters-Stone, Joachim Wiskemann, Sveinung Berntsen, Laurien M. Buffart

Research outputs 2022 to 2026

Introduction: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. Methods: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients …


The Role Of Diet And Gut Microbiota In Alzheimer’S Disease, D. M.Sithara Dissanayaka, Vijay Jayasena, Stephanie R. Rainey-Smith, Ralph N. Martins, W. M.A.D.Binosha Fernando Feb 2024

The Role Of Diet And Gut Microbiota In Alzheimer’S Disease, D. M.Sithara Dissanayaka, Vijay Jayasena, Stephanie R. Rainey-Smith, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD), the most prevalent form of dementia, is characterized by the accumulation of amyloid-beta (A ) plaques and hyperphosphorylated tau tangles. Currently, Alzheimer’s disease (AD) impacts 50 million individuals, with projections anticipating an increase to 152 million by the year 2050. Despite the increasing global prevalence of AD, its underlying pathology remains poorly understood, posing challenges for early diagnosis and treatment. Recent research suggests a link between gut dysbiosis and the aggregation of A , the development of tau proteins, and the occurrence of neuroinflammation and oxidative stress are associated with AD. However, investigations into the gut–brain axis …


Inulin-Based Formulations As An Emerging Therapeutic Strategy For Cancer: A Comprehensive Review, Eswara Naga H K Ghali, Pranav, Subhash Chauhan, Murali M. Yallapu Feb 2024

Inulin-Based Formulations As An Emerging Therapeutic Strategy For Cancer: A Comprehensive Review, Eswara Naga H K Ghali, Pranav, Subhash Chauhan, Murali M. Yallapu

School of Medicine Publications

Highlights

  • Inulin is a naturally occurring prebiotic fiber with therapeutic roles.

  • Inulin can act as an excellent carrier for drug delivery in cancer therapy.

  • Inulin exhibits an improved therapeutic efficacy in its combination treatments.

  • Inulin interventions activate phagocytosis and the TLR4 signaling pathway.

Abstract

Cancer stands as the second leading cause of death in the United States (US). Most chemotherapeutic agents exhibit severe adverse effects that are attributed to exposure of drugs to off-target tissues, posing a significant challenge in cancer therapy management. In recent years, inulin, a naturally occurring prebiotic fiber has gained substantial attention for its potential in …


Using Mobile Technology For Family-Based Prevention In Families With Low Incomes: Lessons From A Randomized Controlled Trial Of A Childhood Obesity Prevention Program, Thomas G Power, Susan S Baker, Karen V Barale, M Catalina Aragón, Jane D Lanigan, Louise Parker, Karina Silva Garcia, Garry Auld, Nilda Micheli, Sheryl O Hughes Feb 2024

Using Mobile Technology For Family-Based Prevention In Families With Low Incomes: Lessons From A Randomized Controlled Trial Of A Childhood Obesity Prevention Program, Thomas G Power, Susan S Baker, Karen V Barale, M Catalina Aragón, Jane D Lanigan, Louise Parker, Karina Silva Garcia, Garry Auld, Nilda Micheli, Sheryl O Hughes

Faculty, Staff and Students Publications

Researchers are increasingly using web-based technologies to deliver family-based, prevention programming. Few studies have examined the success of such approaches for families with low incomes. The purpose of this study was to describe the level of in-class and online engagement in a childhood obesity prevention program for parents with low incomes, to examine the demographic correlates of parent engagement, and to examine dosage effects on parental feeding outcomes as a function of online exposure. All participants attended in-class nutrition education classes (Eating Smart · Being Active) as part of the Expanded Food and Nutrition Education Program (EFNEP) in Colorado and …


Matr3 Pathogenic Variants Differentially Impair Its Cryptic Splicing Repression Function, Mashiat Khan, Xiao Xiao Lily Chen, Michelle Dias, Jhune Rizsan Santos, Sukhleen Kour, Justin You, Rebekah Van Bruggen, Mohieldin M M Youssef, Ying-Wooi Wan, Zhandong Liu, Jill A Rosenfeld, Qiumin Tan, Udai Bhan Pandey, Hari Krishna Yalamanchili, Jeehye Park Feb 2024

Matr3 Pathogenic Variants Differentially Impair Its Cryptic Splicing Repression Function, Mashiat Khan, Xiao Xiao Lily Chen, Michelle Dias, Jhune Rizsan Santos, Sukhleen Kour, Justin You, Rebekah Van Bruggen, Mohieldin M M Youssef, Ying-Wooi Wan, Zhandong Liu, Jill A Rosenfeld, Qiumin Tan, Udai Bhan Pandey, Hari Krishna Yalamanchili, Jeehye Park

Duncan NRI Faculty and Staff Publications

Matrin-3 (MATR3) is an RNA-binding protein implicated in neurodegenerative and neurodevelopmental diseases. However, little is known regarding the role of MATR3 in cryptic splicing within the context of functional genes and how disease-associated variants impact this function. We show that loss of MATR3 leads to cryptic exon inclusion in many transcripts. We reveal that ALS-linked S85C pathogenic variant reduces MATR3 solubility but does not impair RNA binding. In parallel, we report a novel neurodevelopmental disease-associated M548T variant, located in the RRM2 domain, which reduces protein solubility and impairs RNA binding and cryptic splicing repression functions of MATR3. Altogether, our research …


Adverse Metabolic Phenotypes In Parenterally Fed Neonatal Pigs Do Not Persist Into Adolescence, Sarah K Elefson, Barbara Stoll, Teresa A Davis, Marta L Fiorotto, Samer W El-Kadi, Kenneth Genovese, Thomas Thymann, Per T Sangild, Douglas G Burrin Feb 2024

Adverse Metabolic Phenotypes In Parenterally Fed Neonatal Pigs Do Not Persist Into Adolescence, Sarah K Elefson, Barbara Stoll, Teresa A Davis, Marta L Fiorotto, Samer W El-Kadi, Kenneth Genovese, Thomas Thymann, Per T Sangild, Douglas G Burrin

Faculty, Staff and Students Publications

BACKGROUND: Nutrition during fetal and neonatal life is an important determinant for the risk of adult-onset diseases, especially type 2 diabetes and obesity.

OBJECTIVES: We aimed to determine whether total parenteral nutrition (TPN) compared with enteral formula feeding [enteral nutrition (EN)] in term piglets during the first 2 wk after birth would increase the long-term (5-mo) development of metabolic syndrome phenotypes with adverse glucose homeostasis, fatty liver disease, and obesity.

METHODS: Neonatal female pigs were administered TPN (n = 12) or fed enterally with a liquid enteral milk-replacer formula (EN, n = 12) for 14 d. After transitioning TPN pigs …


Faster Discharge With Lactated Ringers Than Normal Saline In First 72 H Of Acute Pancreatitis: A Multicenter Randomized Trial, Peter R Farrell, Angelica W Despain, Peter Farmer, Leslie M Farrell, Bryan Greenfield, Michael E Rogers, Lindsey Hornung, Esther Kim, Ryan Pearman, Beemnet Neway, Tyler Thompson, James E Heubi, Sona Sehgal, Rana Amoury, Maisam Abu-El-Haija Feb 2024

Faster Discharge With Lactated Ringers Than Normal Saline In First 72 H Of Acute Pancreatitis: A Multicenter Randomized Trial, Peter R Farrell, Angelica W Despain, Peter Farmer, Leslie M Farrell, Bryan Greenfield, Michael E Rogers, Lindsey Hornung, Esther Kim, Ryan Pearman, Beemnet Neway, Tyler Thompson, James E Heubi, Sona Sehgal, Rana Amoury, Maisam Abu-El-Haija

Faculty, Staff and Students Publications

OBJECTIVES: Data driven strategies for acute pancreatitis (AP) in pediatrics are limited; adult data suggests lactated ringers (LR) compared to normal saline (NS) resulted in favorable outcomes, but has not been studied in pediatrics. Our objective was to evaluate the efficacy of LR during the first 48 h of an AP episode compared with NS.

STUDY DESIGN: A multi-site randomized controlled clinical trial, from 2015 to 2020 (Clinical Trials.gov NCT03242473). Patients were randomized to exclusively LR or NS for the first 48 hours. Primary outcomes were C-Reactive Protein (CRP) values on admission, 24 and 48 hours. Secondary outcomes …


2024 4-H Volunteer Leader Conference Workshop Descriptions, Nh 4h Unh Cooperative Extension Feb 2024

2024 4-H Volunteer Leader Conference Workshop Descriptions, Nh 4h Unh Cooperative Extension

UNH Cooperative Extension

No abstract provided.


Ubiquitous Filter Feeders Shape Open Ocean Microbial Community Structure And Function, Anne W. Thompson, Györgyi Nyerges, Kylee M. Brevick, Kelly Sutherland Feb 2024

Ubiquitous Filter Feeders Shape Open Ocean Microbial Community Structure And Function, Anne W. Thompson, Györgyi Nyerges, Kylee M. Brevick, Kelly Sutherland

Biology Faculty Publications and Presentations

The mechanism of mortality plays a large role in how microorganisms in the open ocean contribute to global energy and nutrient cycling. Salps are ubiquitous pelagic tunicates that are a well-known mortality source for large phototrophic microorganisms in coastal and high-latitude systems, but their impact on the immense populations of smaller prokaryotes in the tropical and subtropical open ocean gyres is not well quantified. We used robustly quantitative techniques to measure salp clearance and enrichment of specific microbial functional groups in the North Pacific Subtropical Gyre, one of the largest ecosystems on Earth. We discovered that salps are a previously …


The Ddhd2-Stxbp1 Interaction Mediates Long-Term Memory Via Generation Of Saturated Free Fatty Acids, Isaac O Akefe, Saber H Saber, Benjamin Matthews, Bharat G Venkatesh, Rachel S Gormal, Daniel G Blackmore, Suzy Alexander, Emma Sieriecki, Yann Gambin, Jesus Bertran-Gonzalez, Nicolas Vitale, Yann Humeau, Arnaud Gaudin, Sevannah A Ellis, Alysee A Michaels, Mingshan Xue, Benjamin Cravatt, Merja Joensuu, Tristan P Wallis, Frédéric A Meunier Feb 2024

The Ddhd2-Stxbp1 Interaction Mediates Long-Term Memory Via Generation Of Saturated Free Fatty Acids, Isaac O Akefe, Saber H Saber, Benjamin Matthews, Bharat G Venkatesh, Rachel S Gormal, Daniel G Blackmore, Suzy Alexander, Emma Sieriecki, Yann Gambin, Jesus Bertran-Gonzalez, Nicolas Vitale, Yann Humeau, Arnaud Gaudin, Sevannah A Ellis, Alysee A Michaels, Mingshan Xue, Benjamin Cravatt, Merja Joensuu, Tristan P Wallis, Frédéric A Meunier

Faculty, Staff and Students Publications

The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain. Furthermore, DDHD2 loss also decreases memory performance in reward-based learning and spatial memory …


Long-Term Non-Progression And Risk Factors For Disease Progression Among Children Living With Hiv In Botswana And Uganda: A Retrospective Cohort Study, Samuel Kyobe, Grace Kisitu, Savannah Mwesigwa, John Farirai, Eric Katagirya, Gaone Retshabile, Lesedi Williams, Angela Mirembe, Lesego Ketumile, Misaki Wayengera, John Mukisa, Gaseene Sebetso, Thabo Diphoko, Marion Amujal, Edgar Kigozi, Fred Katabazi, Ronald Oceng, Busisiwe Mlotshwa, Koketso Morapedi, Betty Nsangi, Edward Wampande, Masego Tsimako, Chester Brown, Ishmael Kasvosve, Moses Joloba, Gabriel Anabwani, Sununguko Mpoloka, Graeme Mardon, Adeodata Kekitiinwa, Neil A Hanchard, Jacqueline Kyosiimire-Lugemwa, Mogomotsi Matshaba, Dithan Kiragga Feb 2024

Long-Term Non-Progression And Risk Factors For Disease Progression Among Children Living With Hiv In Botswana And Uganda: A Retrospective Cohort Study, Samuel Kyobe, Grace Kisitu, Savannah Mwesigwa, John Farirai, Eric Katagirya, Gaone Retshabile, Lesedi Williams, Angela Mirembe, Lesego Ketumile, Misaki Wayengera, John Mukisa, Gaseene Sebetso, Thabo Diphoko, Marion Amujal, Edgar Kigozi, Fred Katabazi, Ronald Oceng, Busisiwe Mlotshwa, Koketso Morapedi, Betty Nsangi, Edward Wampande, Masego Tsimako, Chester Brown, Ishmael Kasvosve, Moses Joloba, Gabriel Anabwani, Sununguko Mpoloka, Graeme Mardon, Adeodata Kekitiinwa, Neil A Hanchard, Jacqueline Kyosiimire-Lugemwa, Mogomotsi Matshaba, Dithan Kiragga

Faculty, Staff and Students Publications

OBJECTIVES: We utilize a large retrospective study cohort derived from electronic medical records to estimate the prevalence of long-term non-progression (LTNP) and determine the factors associated with progression among children infected with HIV in Botswana and Uganda.

METHODS: Electronic medical records from large tertiary HIV clinical centers in Botswana and Uganda were queried to identify LTNP children 0-18 years enrolled between June 2003 and May 2014 and extract demographic and nutritional parameters. Multivariate subdistribution hazard analyses were used to examine demographic factors and nutritional status in progression in the pre-antiretroviral therapy era.

RESULTS: Between the two countries, 14,246 antiretroviral therapy-naïve …


The Human Vaginal Microbiota: From Clinical Medicine To Models To Mechanisms, Samantha Ottinger, Clare M Robertson, Holly Branthoover, Kathryn A Patras Feb 2024

The Human Vaginal Microbiota: From Clinical Medicine To Models To Mechanisms, Samantha Ottinger, Clare M Robertson, Holly Branthoover, Kathryn A Patras

Faculty, Staff and Students Publications

The composition of the vaginal microbiota is linked to numerous reproductive health problems, including increased susceptibility to infection, pregnancy complications, and impaired vaginal tissue repair; however, the mechanisms contributing to these adverse outcomes are not yet fully defined. In this review, we highlight recent clinical advancements associating vaginal microbiome composition and function with health outcomes. Subsequently, we provide a summary of emerging models employed to identify microbe-microbe interactions contributing to vaginal health, including metagenomic sequencing, multi-omics approaches, and advances in vaginal microbiota cultivation. Last, we review new in vitro, ex vivo, and in vivo models, such as organoids and humanized …