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Functional Investigation Of A Putative Calcium-Binding Site Involved In The Inhibition Of Inositol 1,4, 5-Trisphosphate Receptor Activity, Vikas Arige, Larry E Wagner, Sundeep Malik, Mariah R Baker, Guizhen Fan, Irina I Serysheva, David I Yule Mar 2025

Functional Investigation Of A Putative Calcium-Binding Site Involved In The Inhibition Of Inositol 1,4, 5-Trisphosphate Receptor Activity, Vikas Arige, Larry E Wagner, Sundeep Malik, Mariah R Baker, Guizhen Fan, Irina I Serysheva, David I Yule

Faculty, Staff and Student Publications

The regulation of inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) activity is thought to define the spatiotemporal patterns of Ca2+ signals necessary for the appropriate activation of downstream effectors. The binding of both IP3 and Ca2+ is obligatory for IP3R channel opening. Ca2+ however regulates IP3R activity in a biphasic manner. Ca2+ binding to a high-affinity pocket formed by the third armadillo repeat domain and linker domain promotes IP3R channel opening without altering the Ca2+ dependency for channel inactivation. These data suggest that a distinct low-affinity Ca2+-binding site is responsible for the reduction in IP3R activity at higher [Ca2+]. We mutated a …


Pilot Screening For Prodromal Parkinson’S Disease In Post-9/11 Veterans With Probable Rapid Eye Movement Sleep Behavior Disorder, Melissa B Jones, Dakota Broadway, Taryn White, George R Jackson, Supriya Singh, Ruosha Li, Erik K St Louis, Laura E Marsh, Ricardo E Jorge Mar 2025

Pilot Screening For Prodromal Parkinson’S Disease In Post-9/11 Veterans With Probable Rapid Eye Movement Sleep Behavior Disorder, Melissa B Jones, Dakota Broadway, Taryn White, George R Jackson, Supriya Singh, Ruosha Li, Erik K St Louis, Laura E Marsh, Ricardo E Jorge

Faculty, Staff and Students Publications

This pilot examined prodromal markers in post-9/11 Veterans with TBI and probable REM sleep behavior disorder (N = 12). RBD was confirmed in 5 of 10 (50 %) participants with polysomnography. Veterans with subthreshold parkinsonism had lower olfactory scores. Future studies should quantify REM sleep without atonia and include broader markers.


Disrupting Tymp-Mediated Pathways To Block Lymph Node Metastasis In Ovarian Cancer, Emine Bayraktar Mar 2025

Disrupting Tymp-Mediated Pathways To Block Lymph Node Metastasis In Ovarian Cancer, Emine Bayraktar

Dissertations and Theses (Open Access)

Historically, ovarian cancer (OC) was thought to metastasize by surface-to-surface spread, but recent developments have yielded a new understanding of the paths of metastatic spread. In epithelial ovarian cancer, the mechanisms driving lymph node (LN) metastasis are poorly understood, and it remains unclear whether omental metastasis occurs in parallel with LN metastasis. Utilizing comparative transcriptomic and proteomic profiling of primary tumors, LN metastases, and omental metastases, we identified significant upregulation of thymidine phosphorylase (TYMP) in LN metastases compared to primary and omental tumor sites. Functional studies in murine models demonstrated that TYMP silencing significantly suppressed LN metastasis, underscoring TYMP as …


Community Engagement Approaches And Lessons Learned: A Case Study Of The Precise Pregnancy Cohort Study In Kenya, Onesmus Wanje, Angela Koech, Maggie Woo Kinshella, Grace Mwashigadi, Alice Kombo, Grace Maitha, Nathan Barreh, Hiten D. Mistry, Marianne Vidler, Rachel Craik Mar 2025

Community Engagement Approaches And Lessons Learned: A Case Study Of The Precise Pregnancy Cohort Study In Kenya, Onesmus Wanje, Angela Koech, Maggie Woo Kinshella, Grace Mwashigadi, Alice Kombo, Grace Maitha, Nathan Barreh, Hiten D. Mistry, Marianne Vidler, Rachel Craik

Centre of Excellence in Women and Child Health

Community engagement (CE) has been recommended as an important ethical consideration for health research to enhance informed consent and exchange knowledge between researchers and community members. The purpose of this paper is to describe how CE was developed and delivered for the PRECISE prospective pregnancy cohort study in Kenya. PRECISE enrolled pregnant women in antenatal care, followed them up to the postpartum period, and collected data and biological samples to enable the study of placental disorders in sub-Saharan Africa. Initially CE was aimed at informing the community about the study, establishing communitywide acceptance of the research and addressing concerns about …


Explainable Neural Networks With Guarantee: A Sparse Estimation Approach, Antoine Ledent, Peng Liu Mar 2025

Explainable Neural Networks With Guarantee: A Sparse Estimation Approach, Antoine Ledent, Peng Liu

Research Collection School Of Computing and Information Systems

Balancing predictive power and interpretability has long been a challenging research area, particularly in powerful yet complex models like neural networks, where nonlinearity obstructs direct interpretation. This paper introduces a novel approach to constructing an explainable neural network that harmonizes predictiveness and explainability. Our model is designed as a linear combination of a sparse set of jointly learned features, each derived from a different trainable function applied to a single 1-dimensional input feature. Leveraging the ability to learn arbitrarily complex relationships, our neural network architecture enables automatic selection of a sparse set of important features, with the final prediction being …


Dr. Tongue: Sign-Oriented Multi-Label Detection For Remote Tongue Diagnosis, Yiliang Chen, Steven S. C. Ho, Cheng Xu, Yao Jie Xie, Wing Fai Yeung, Shengfeng He, Jing Qin Mar 2025

Dr. Tongue: Sign-Oriented Multi-Label Detection For Remote Tongue Diagnosis, Yiliang Chen, Steven S. C. Ho, Cheng Xu, Yao Jie Xie, Wing Fai Yeung, Shengfeng He, Jing Qin

Research Collection School Of Computing and Information Systems

Tongue diagnosis is a vital tool in Western and Traditional Chinese Medicine, providing key insights into a patient's health by analyzing tongue attributes. The COVID-19 pandemic has heightened the need for accurate remote medical assessments, emphasizing the importance of precise tongue attribute recognition via telehealth. To address this, we propose a Sign-Oriented multi-label Attributes Detection framework. Our approach begins with an adaptive tongue feature extraction module that standardizes tongue images and mitigates environmental factors. This is followed by a Sign-oriented Network (SignNet) that identifies specific tongue attributes, emulating the diagnostic process of experienced practitioners and enabling comprehensive health evaluations. To …


Safety And Efficacy Of Dtx401, An Aav8-Mediated Liver-Directed Gene Therapy, In Adults With Glycogen Storage Disease Type I A (Gsdia), David A Weinstein, Terry G Derks, David F Rodriguez-Buritica, Ayesha Ahmad, María-Luz Couce, John J Mitchell, Rebecca Riba-Wolman, Malaya Mount, Julieta Bonvin Sallago, Katalin M Ross, Melanie M Van Der Klauw, Foekje De Boer, Caroline Van Der Schaaf, Heather Saavedra, Miguel Martínez-Olmos, Elvis Atanga, Asad Hosseini, Deepali Mitragotri, Eric Crombez Mar 2025

Safety And Efficacy Of Dtx401, An Aav8-Mediated Liver-Directed Gene Therapy, In Adults With Glycogen Storage Disease Type I A (Gsdia), David A Weinstein, Terry G Derks, David F Rodriguez-Buritica, Ayesha Ahmad, María-Luz Couce, John J Mitchell, Rebecca Riba-Wolman, Malaya Mount, Julieta Bonvin Sallago, Katalin M Ross, Melanie M Van Der Klauw, Foekje De Boer, Caroline Van Der Schaaf, Heather Saavedra, Miguel Martínez-Olmos, Elvis Atanga, Asad Hosseini, Deepali Mitragotri, Eric Crombez

Faculty, Staff and Student Publications

Glycogen storage disease type Ia (GSDIa) is a rare, life‐threatening, inherited carbohydrate metabolism disorder caused by glucose‐6‐phosphatase (G6Pase) deficiency, which is essential for glycogenolysis and gluconeogenesis. GSDIa management includes a strict medically prescribed diet that typically includes daily uncooked cornstarch doses, including overnight, to maintain euglycemia. DTX401 is an investigational adeno‐associated virus serotype 8 vector expressing the human G6PC1 gene that encodes G6Pase. This open‐label, phase 1/2, dose‐escalation, 52‐week gene therapy trial evaluated the safety and efficacy of a single DTX401 infusion in 12 adults with GSDIa (ClinicalTrials.gov Identifier: NCT03517085). Three participants in Cohort 1 received DTX401 2.0 × …


Caloric Restriction And Telomere Preservation In Tert Knockout Adipocyte Progenitors Does Not Rescue Mice From Metabolic Dysfunction Due To A Tert Function In Adipocyte Mitochondria, Zhanguo Gao, Yongmei Yu, Kristin Eckel-Mahan, Mikhail G Kolonin Mar 2025

Caloric Restriction And Telomere Preservation In Tert Knockout Adipocyte Progenitors Does Not Rescue Mice From Metabolic Dysfunction Due To A Tert Function In Adipocyte Mitochondria, Zhanguo Gao, Yongmei Yu, Kristin Eckel-Mahan, Mikhail G Kolonin

The Brown Foundation: Institute of Molecular Medicine

Inactivation of telomerase (TERT) in adipocyte progenitor cells (APC) expedites telomere attrition, and the onset of diabetes in mice fed high-fat diet (HFD), which promotes APC over-proliferation and replicative senescence. Here, we show that time-restricted feeding or caloric restriction in the postnatal development of mice subsequently subjected to HFD prevents telomere attrition but not glucose intolerance. This metabolic effect of dietary intervention was not observed for mice with TERT KO in endothelial or myeloid cells. To characterize the telomere-independent effects of TERT in the APC lineage, we analyzed mice with TERT knockout in mature adipocytes (AD-TERT-KO), which do not proliferate …


Reevaluating Anti-Inflammatory Therapy: Targeting Senescence To Balance Anti-Cancer Efficacy And Vascular Disease, Bernardo Casso-Chapa, Norma Alicia Vazquez González, Nhat-Tu Le, Nicolas L Palaskas, Kevin T Nead, Lydia P Eutsey, Venkata S K Samanthapudi, Abigail M Osborn, Jonghae Lee, Gilbert Mejia, Oanh Hoang, Steven H Lin, Anita Deswal, Joerg Herrmann, Guangyu Wang, James L Kirkland, Sunil Krishnan, Xander H T Wehrens, Eduardo N Chini, Syed Wamique Yusuf, Cezar A Iliescu, Abhishek Jain, Jared K Burks, Erin Seeley, Philip L Lorenzi, Khanh M Chau, Keila C Ostos-Mendoza, Isabella M Grumbach, Paul S Brookes, Nordin M J Hanssen, Menno P J De Winther, Laurent Yvan-Charvet, Sivareddy Kotla, Keri Schadler, Jun-Ichi Abe Mar 2025

Reevaluating Anti-Inflammatory Therapy: Targeting Senescence To Balance Anti-Cancer Efficacy And Vascular Disease, Bernardo Casso-Chapa, Norma Alicia Vazquez González, Nhat-Tu Le, Nicolas L Palaskas, Kevin T Nead, Lydia P Eutsey, Venkata S K Samanthapudi, Abigail M Osborn, Jonghae Lee, Gilbert Mejia, Oanh Hoang, Steven H Lin, Anita Deswal, Joerg Herrmann, Guangyu Wang, James L Kirkland, Sunil Krishnan, Xander H T Wehrens, Eduardo N Chini, Syed Wamique Yusuf, Cezar A Iliescu, Abhishek Jain, Jared K Burks, Erin Seeley, Philip L Lorenzi, Khanh M Chau, Keila C Ostos-Mendoza, Isabella M Grumbach, Paul S Brookes, Nordin M J Hanssen, Menno P J De Winther, Laurent Yvan-Charvet, Sivareddy Kotla, Keri Schadler, Jun-Ichi Abe

The Brown Foundation: Institute of Molecular Medicine

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression. Anti-inflammatory therapy, therefore, presents a unique dilemma for cancer survivors: while it may decrease cardiovascular risk, it might also promote cancer growth and metastasis by suppressing the immune response. Senescence presents a potentially targetable solution to this challenge; senescence increases the risk of both cancer therapy resistance and vascular disease. Exercise, notably, shows promise in delaying this premature senescence, potentially …


2025 March, Morehead State University. Office Of Communications & Marketing. Mar 2025

2025 March, Morehead State University. Office Of Communications & Marketing.

Morehead State Press Release Archive, 1961 to the Present

Press releases for March of 2025.


Sources Of Well-Being And Cardiovascular Health: A Mixed Methods Investigation From The Midus Study, Julia K. Boehm, Monica Adams, Jennifer Morozink Boylan Mar 2025

Sources Of Well-Being And Cardiovascular Health: A Mixed Methods Investigation From The Midus Study, Julia K. Boehm, Monica Adams, Jennifer Morozink Boylan

Psychology Faculty Articles and Research

Objective

Using mixed methods, we investigated whether different sources of well-being were associated with better cardiovascular health.

Methods

Data came from adults (55% women; 19% Black, 75% White) with biomarker data from the Midlife in the United States (MIDUS) Study. At the second wave and in a refresher cohort, participants answered the question “What do you do to make your life go well?” Judges evaluated each response for the presence of 12 sources of well-being (e.g., positive relationships, faith, health maintenance). Participants were also assessed on 8 components of cardiovascular health at two waves, an average of 12 years apart. …


Brain-Type Natriuretic Peptide Is A Useful Biomarker Of Cardiovascular Disease And Predictor Of Cardiac-Related Mortality In Chimpanzees (Pan Troglodytes), Angela M. Achorn, Carolyn L. Hodo, Martha E. Hensel, Elizabeth R. Magden, Stephanie J. Buchl Mar 2025

Brain-Type Natriuretic Peptide Is A Useful Biomarker Of Cardiovascular Disease And Predictor Of Cardiac-Related Mortality In Chimpanzees (Pan Troglodytes), Angela M. Achorn, Carolyn L. Hodo, Martha E. Hensel, Elizabeth R. Magden, Stephanie J. Buchl

Anthropology Faculty Publications

OBJECTIVE

To validate the use of brain-type natriuretic peptide (BNP) for detecting and monitoring cardiac dysfunction in captive chimpanzees (Pan troglodytes).

METHODS

We analyzed cross-sectional (N = 175) and longitudinal (N = 76) BNP, echocardiogram, ECG, and pathology data from living and deceased captive chimpanzees to examine age and sex effects and to assess the usefulness of BNP for detecting cardiovascular disease and predicting mortality. The study period was from July 2010 through October 2024.

RESULTS

Brain-type natriuretic peptide values were significantly associated with age, and males exhibited significantly higher BNP values than females. Brain-type natriuretic peptide values …


Leveraging Artificial Intelligence And Machine Learning To Accelerate Discovery Of Disease-Modifying Therapies In Type 1 Diabetes., Melanie R. Shapiro, Erin M. Tallon, Matthew E. Brown, Amanda L. Posgai, Mark A. Clements, Todd M. Brusko Mar 2025

Leveraging Artificial Intelligence And Machine Learning To Accelerate Discovery Of Disease-Modifying Therapies In Type 1 Diabetes., Melanie R. Shapiro, Erin M. Tallon, Matthew E. Brown, Amanda L. Posgai, Mark A. Clements, Todd M. Brusko

Manuscripts, Articles, Book Chapters and Other Papers

Progress in developing therapies for the maintenance of endogenous insulin secretion in, or the prevention of, type 1 diabetes has been hindered by limited animal models, the length and cost of clinical trials, difficulties in identifying individuals who will progress faster to a clinical diagnosis of type 1 diabetes, and heterogeneous clinical responses in intervention trials. Classic placebo-controlled intervention trials often include monotherapies, broad participant populations and extended follow-up periods focused on clinical endpoints. While this approach remains the 'gold standard' of clinical research, efforts are underway to implement new approaches harnessing the power of artificial intelligence and machine learning …


Can Oral Caffeine Decrease Postoperative Opioid Consumption Following Posterior Spinal Fusion In Adolescent Idiopathic Scoliosis? A Randomized Placebo-Controlled Trial., Anne E. Stuedemann, Richard M. Schwend, K Aaron Shaw, Nicolette Saddler, Michon Huston, Michael Benvenuti, Julia Leamon, Ashley K. Sherman, John Anderson Mar 2025

Can Oral Caffeine Decrease Postoperative Opioid Consumption Following Posterior Spinal Fusion In Adolescent Idiopathic Scoliosis? A Randomized Placebo-Controlled Trial., Anne E. Stuedemann, Richard M. Schwend, K Aaron Shaw, Nicolette Saddler, Michon Huston, Michael Benvenuti, Julia Leamon, Ashley K. Sherman, John Anderson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Current studies have examined the efficacy of opioid-sparing analgesics primarily in adult surgical populations, while fewer guide pediatric postoperative pain treatment. Caffeine exerts most of its biological effects by binding to adenosine receptors, which are important for modifying pain and inflammation. Caffeine's ability to modulate pain following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) has not been previously assessed.

METHODS: The hospital investigational drug study (IDS) pharmacy provided either a treatment dose or placebo dose of caffeine to be given to the patient and was also in charge of randomization for the study.

RESULTS: There were 24 …


Genetic Characterization Of A Large Cohort Of Individuals With A Clinical Suspicion Of Hypophosphatasia In The United States., Eric T. Rush, Guillermo Del Angel, Juan Dong, Toby Bates, Robert D. Steiner, Allison Cox Mar 2025

Genetic Characterization Of A Large Cohort Of Individuals With A Clinical Suspicion Of Hypophosphatasia In The United States., Eric T. Rush, Guillermo Del Angel, Juan Dong, Toby Bates, Robert D. Steiner, Allison Cox

Manuscripts, Articles, Book Chapters and Other Papers

Hypophosphatasia (HPP) is a rare metabolic disease resulting from variants in ALPL, inherited in an either autosomal recessive or autosomal dominant manner. Sponsored clinical ALPL testing was offered in the US for individuals with a clinical suspicion of HPP. Gene variants were assessed to determine the likelihood of identifying disease-causing variants, uncover genotype-phenotype relationships, and for further understanding of ALPL variants in the US HPP population. Variants were detected by Sanger sequencing and classified as pathogenic or likely pathogenic (P/LP; positive test result), variant(s) of uncertain significance (indeterminate test result), benign or likely benign (negative test result), or no variants …


The Anchor: March 2025, Issue Three, Hope College Mar 2025

The Anchor: March 2025, Issue Three, Hope College

The Anchor: 2025

The Anchor began in 1887 and was first issued weekly in 1914. Covering national and campus news alike, Hope College’s student-run newspaper has grown over the years to encompass over two-dozen editors, reporters, and staff. For much of The Anchor's history, the latest issue was distributed across campus each Wednesday throughout the academic school year (with few exceptions). In recent years The Anchor moved to monthly print issues and a more frequently updated website. The Anchor is now published in print twice per academic semester. Occasionally, the volume and/or issue numbering is irregular.


Protective Effects Of Nerolidol On Thrombotic Events, Systemic Inflammation, Oxidative Stress, And Dna Damage Following Pulmonary Exposure To Diesel Exhaust Particles, Naserddine Hamadi, Sumaya Beegam, Nur Elena Zaaba, Ozaz Elzaki, Alreem Alderei, Maha Alfalahi, Shamma Alhefeiti, Dana Alnaqbi, Salama Alshamsi, Abderrahim Nemmar Mar 2025

Protective Effects Of Nerolidol On Thrombotic Events, Systemic Inflammation, Oxidative Stress, And Dna Damage Following Pulmonary Exposure To Diesel Exhaust Particles, Naserddine Hamadi, Sumaya Beegam, Nur Elena Zaaba, Ozaz Elzaki, Alreem Alderei, Maha Alfalahi, Shamma Alhefeiti, Dana Alnaqbi, Salama Alshamsi, Abderrahim Nemmar

All Works

Background/Objectives: Inhalation of environmental particulate air pollution has been reported to cause pulmonary and systemic events including coagulation disturbances, systemic inflammation, and oxidative stress. Nerolidol, a naturally occurring sesquiterpene alcohol, has effective antioxidant and anti-inflammatory effects. Hence, the aim in the present investigation was to evaluate the potential ameliorative effects of nerolidol on the coagulation and systemic actions induced by pulmonary exposure to diesel exhaust particles (DEPs). Methods: Nerolidol (100 mg/kg) was given to mice by oral gavage one hour before the intratracheal instillation of DEPs (0.5 mg/kg), and 24 h later various markers of coagulation and systemic toxicity were …


Multi-Omics Delineate Growth Factor Network Underlying Exercise Effects In An Alzheimer’S Mouse Model, Xin Li, Chaozhong Liu, Wenbo Li, Guantong Qi, Yanwan Dai, Chaohao Gu, Yuxiang Sun, Wenjun Zhou, Veronica C Ciliberto, Jing Liang, Udhaya Kumar S, Dongyin Guan, Zhaoyong Hu, Hui Zheng, Zhandong Liu, Hu Chen, Ying-Wooi Wan, Zheng Sun Mar 2025

Multi-Omics Delineate Growth Factor Network Underlying Exercise Effects In An Alzheimer’S Mouse Model, Xin Li, Chaozhong Liu, Wenbo Li, Guantong Qi, Yanwan Dai, Chaohao Gu, Yuxiang Sun, Wenjun Zhou, Veronica C Ciliberto, Jing Liang, Udhaya Kumar S, Dongyin Guan, Zhaoyong Hu, Hui Zheng, Zhandong Liu, Hu Chen, Ying-Wooi Wan, Zheng Sun

Duncan NRI Faculty and Staff Publications

Introduction: Physical exercise is a primary defense against age-related cognitive decline and Alzheimer's disease (AD).

Methods: We conducted single-nucleus transcriptomic and chromatin accessibility analyses (snRNA-seq and snATAC-seq) on the hippocampus of mice carrying mutations in the amyloid precursor protein gene (APPNL-G-F) following prolonged voluntary wheel-running exercise.

Results: Exercise mitigates amyloid-induced changes in transcriptome and chromatin accessibility through cell type-specific regulatory networks converging on growth factor signaling, particularly the epidermal growth factor receptor (EGFR) signaling. The beneficial effects of exercise on neurocognition can be blocked by pharmacological inhibition of EGFR and its downstream PI3K signaling. Exercise leads to elevated levels of …


Btx Photodegradation Using Synthetic Nano Photocatalysts, Firdos Abdulla, Zainab Shnain, Asawer Alwaisit, Mohammad Abid Mar 2025

Btx Photodegradation Using Synthetic Nano Photocatalysts, Firdos Abdulla, Zainab Shnain, Asawer Alwaisit, Mohammad Abid

Journal of Applied Sciences and Nanotechnology

A photocatalytic tapered bubble column reactor was utilized to extract benzene, toluene, and xylene (BTX) organic pollutants from petroleum effluent. The reactor had an internal diameter that increased from 0.07 meters at the bottom to 0.17 meters at the top, a tapered angle of 1.6 degrees, a length of 1.8 meters, and a capacity of approximately 20 liters. Additionally, the reactor was equipped with a Fe-doped TiO2 catalyst. Different air flow rates (0-3 L/min), contact periods (0-120 min), and liquid flow rates (160-600 L/hr) were used in the photocatalyst with four submerged LED lamps (wavelength of 200–550 nm). Each of …


Phage-Antibiotic Synergy: Enhancing Efficacy Against Multidrug-Resistant Bacteria, Anwer Faisal, Bassam Mahmood, Baraa Saeed Mar 2025

Phage-Antibiotic Synergy: Enhancing Efficacy Against Multidrug-Resistant Bacteria, Anwer Faisal, Bassam Mahmood, Baraa Saeed

Journal of Applied Sciences and Nanotechnology

The increasing number of bacteria that are resistant to antibiotics poses a major challenge to public health. Therefore, research into new treatment methods is essential to overcome these challenges. Phage treatment is a promising technique to increase the efficacy of antimicrobials against resistant microbes. This review documents the ability of bacteriophages to interact with conventional antibiotics due to their specificity and adaptability to target and control bacterial populations, especially when used in combination with antibiotics. Combination therapy can deliver the lowest effective concentration of antibiotics while reducing toxicity. Research has confirmed that the synergy of phages and antibiotics can disrupt …


Social Media In Advancing Equity And Collaboration In Rheumatology: The Cordiality Review, Ihsane Hmamouchi, Nelly Ziade, Adewale Adebajo, Latika Gupta, Puja Mehta, Angela Migowa, Elena Nikiphorou, Noelle A. Rolle, Didem Saygin, Namrata Singh Mar 2025

Social Media In Advancing Equity And Collaboration In Rheumatology: The Cordiality Review, Ihsane Hmamouchi, Nelly Ziade, Adewale Adebajo, Latika Gupta, Puja Mehta, Angela Migowa, Elena Nikiphorou, Noelle A. Rolle, Didem Saygin, Namrata Singh

Pathology, East Africa

Social media has transformed communication in academia and medicine, offering stakeholders innovative avenues for knowledge exchange and collaboration. The CORDIALITY review (soCial media fOR aDvancing equIty And coLlaboration In rheumaTologY) examines the impact of social media on education and information dissemination, patient education and empowerment, networking and mentorship, and research collaboration within rheumatology, when effectively used. In this narrative review, we consider the opportunities as well as the challenges related to each of these facets of social media use. With a focus on inequities faced globally, we give particular consideration to disparities by gender as they relate to the rheumatology …


Diet-Enhanced Lrg1 Expression Promotes Insulin Hypersecretion And Er Stress In Pancreatic Beta Cells, Desirae D Morales, Jiyoon Ryu, Cong Wei, Jason T Hadley, Maia R Smith, Juli Bai, Juan C Lopez-Alvarenga, Srinivas Mummidi, Ravindranath Duggirala, Jane L Lynch, Feng Liu, Lily Q Dong Mar 2025

Diet-Enhanced Lrg1 Expression Promotes Insulin Hypersecretion And Er Stress In Pancreatic Beta Cells, Desirae D Morales, Jiyoon Ryu, Cong Wei, Jason T Hadley, Maia R Smith, Juli Bai, Juan C Lopez-Alvarenga, Srinivas Mummidi, Ravindranath Duggirala, Jane L Lynch, Feng Liu, Lily Q Dong

Faculty, Staff and Student Publications

Aims/hypothesis: Upregulation of serum leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in diet-induced obesity and metabolic disorders. However, its specific hormonal actions remain unclear. This study aimed to determine whether diet-enhanced serum LRG1 levels promote hyperinsulinaemia by directly stimulating insulin secretion from pancreatic beta cells.

Methods: Human serum samples were obtained from individuals (both male and female) undergoing plastic surgery. Male C57BL/6 wild-type and Lrg1 whole-body knockout (Lrg1KO) mice were fed a 45% high-fat diet, with serum samples collected every 2 weeks to monitor LRG1 and insulin levels throughout diet-induced obesity. MIN6 beta cells were used to investigate the effects …


Causes Of Mortality In The Congenital Disorders Of Glycosylation, Hana Alharbi, Seishu Horikoshi, Sabrina Malone Jenkins, Fernando Scaglia, Christina Lam, Eva Morava, Austin Larson, Andrew C Edmondson Mar 2025

Causes Of Mortality In The Congenital Disorders Of Glycosylation, Hana Alharbi, Seishu Horikoshi, Sabrina Malone Jenkins, Fernando Scaglia, Christina Lam, Eva Morava, Austin Larson, Andrew C Edmondson

Faculty, Staff and Students Publications

Congenital Disorders of Glycosylation (CDG) are a group of some 200 genetic disorders with PMM2-CDG being the most common disease. These disorders individually remain rare with poorly understood natural history (NH) and causes of mortality. We established a NH study for CDG and collected both prospective and retrospective data on CDG outcomes. In the current data set analysis on deceased patients, we describe the clinical phenotype and causes of death for thirty-seven individuals with various genetic causes of CDG. About a third of this cohort were affected with PMM2-CDG. All of the patients presented with multisystem features with involvement of …


The Glu86 Residue In Tbx4 Proves Critical For Human Lung Development, Przemyslaw Szafranski, Tomasz Gambin, Gail Deutsch, Salma A Nassef, Mary Clay Bailey, Debra L Kearney, Paweł Stankiewicz Mar 2025

The Glu86 Residue In Tbx4 Proves Critical For Human Lung Development, Przemyslaw Szafranski, Tomasz Gambin, Gail Deutsch, Salma A Nassef, Mary Clay Bailey, Debra L Kearney, Paweł Stankiewicz

Faculty, Staff and Students Publications

T-box transcription factors are a group of evolutionarily conserved T-box-containing regulators of mesoderm specification and development. Heterozygous single nucleotide variants (SNVs) or copy-number variant (CNV) deletions involving dosage-sensitive TBX4 have been associated with pulmonary arterial hypertension (PAH), ischiocoxopodopatellar syndrome with or without PAH, and lethal lung developmental disorders (LLDDs), including acinar dysplasia (AcDys), congenital alveolar dysplasia (CAD), and other unspecified primary pulmonary hypoplasias. Loss- and gain-of-function variants have been proposed to cause pediatric PAH and LLDDs, and adult forms of PAH, respectively. Of more than 50 missense SNVs scattered across the entire TBX4, only three have been reported in patients …


Predicting Chemotherapy Responsiveness In Gastric Cancer Through Machine Learning Analysis Of Genome, Immune, And Neutrophil Signatures, Shota Sasagawa, Yoshitaka Honma, Xinxin Peng, Kazuhiro Maejima, Koji Nagaoka, Yukari Kobayashi, Ayako Oosawa, Todd A Johnson, Yuki Okawa, Han Liang, Kazuhiro Kakimi, Yasuhide Yamada, Hidewaki Nakagawa Mar 2025

Predicting Chemotherapy Responsiveness In Gastric Cancer Through Machine Learning Analysis Of Genome, Immune, And Neutrophil Signatures, Shota Sasagawa, Yoshitaka Honma, Xinxin Peng, Kazuhiro Maejima, Koji Nagaoka, Yukari Kobayashi, Ayako Oosawa, Todd A Johnson, Yuki Okawa, Han Liang, Kazuhiro Kakimi, Yasuhide Yamada, Hidewaki Nakagawa

Faculty, Staff and Student Publications

Background: Gastric cancer is a major oncological challenge, ranking highly among causes of cancer-related mortality worldwide. This study was initiated to address the variability in patient responses to combination chemotherapy, highlighting the need for personalized treatment strategies based on genomic data.

Methods: We analyzed whole-genome and RNA sequences from biopsy specimens of 65 advanced gastric cancer patients before their chemotherapy treatment. Using machine learning techniques, we developed a model with 123 omics features, such as immune signatures and copy number variations, to predict their chemotherapy outcomes.

Results: The model demonstrated a prediction accuracy of 70-80% in forecasting chemotherapy responses in …


Guidelines For Minimal Reporting Requirements, Design And Interpretation Of Experiments Involving The Use Of Eukaryotic Dual Gene Expression Reporters (Mindr), Gary Loughran, Dmitry E Andreev, Ilya M Terenin, Olivier Namy, Martin Mikl, Martina M Yordanova, C Joel Mcmanus, Andrew E Firth, John F Atkins, Christopher S Fraser, Zoya Ignatova, Shintaro Iwasaki, Joanna Kufel, Ola Larsson, Sebastian A Leidel, Alexander S Mankin, Marco Mariotti, Marvin E Tanenbaum, Ivan Topisirovic, Nora Vázquez-Laslop, Gabriela Viero, Neva Caliskan, Yiwen Chen, Patricia L Clark, Jonathan D Dinman, Philip J Farabaugh, Wendy V Gilbert, Pavel Ivanov, Jeffrey S Kieft, Oliver Mühlemann, Matthew S Sachs, Ivan N Shatsky, Nahum Sonenberg, Anna-Lena Steckelberg, Anne E Willis, Michael T Woodside, Leos Shivaya Valasek, Sergey E Dmitriev, Pavel V Baranov Mar 2025

Guidelines For Minimal Reporting Requirements, Design And Interpretation Of Experiments Involving The Use Of Eukaryotic Dual Gene Expression Reporters (Mindr), Gary Loughran, Dmitry E Andreev, Ilya M Terenin, Olivier Namy, Martin Mikl, Martina M Yordanova, C Joel Mcmanus, Andrew E Firth, John F Atkins, Christopher S Fraser, Zoya Ignatova, Shintaro Iwasaki, Joanna Kufel, Ola Larsson, Sebastian A Leidel, Alexander S Mankin, Marco Mariotti, Marvin E Tanenbaum, Ivan Topisirovic, Nora Vázquez-Laslop, Gabriela Viero, Neva Caliskan, Yiwen Chen, Patricia L Clark, Jonathan D Dinman, Philip J Farabaugh, Wendy V Gilbert, Pavel Ivanov, Jeffrey S Kieft, Oliver Mühlemann, Matthew S Sachs, Ivan N Shatsky, Nahum Sonenberg, Anna-Lena Steckelberg, Anne E Willis, Michael T Woodside, Leos Shivaya Valasek, Sergey E Dmitriev, Pavel V Baranov

Faculty, Staff and Student Publications

Dual reporters encoding two distinct proteins within the same mRNA have had a crucial role in identifying and characterizing unconventional mechanisms of eukaryotic translation. These mechanisms include initiation via internal ribosomal entry sites (IRESs), ribosomal frameshifting, stop codon readthrough and reinitiation. This design enables the expression of one reporter to be influenced by the specific mechanism under investigation, while the other reporter serves as an internal control. However, challenges arise when intervening test sequences are placed between these two reporters. Such sequences can inadvertently impact the expression or function of either reporter, independent of translation-related changes, potentially biasing the results. …


Monte Carlo Modeling Of An Experimental Benchtop L-Shell X-Ray Fluorescence Imaging/Ct System Adopting Two Silicone Drift Detectors, Neerajan Nepal, Amrit Kaphle, Sandun Jayarathna, Sang Hyun Cho Mar 2025

Monte Carlo Modeling Of An Experimental Benchtop L-Shell X-Ray Fluorescence Imaging/Ct System Adopting Two Silicone Drift Detectors, Neerajan Nepal, Amrit Kaphle, Sandun Jayarathna, Sang Hyun Cho

Faculty, Staff and Student Publications

L-shell x-ray fluorescence (XRF) photons induced from gold nanoparticles (GNPs) after being irradiated by an x-ray beam allow for highly sensitive XRF imaging/computed tomography (XFCT) of biological samples containing GNPs at low concentrations on the order of parts-per-million (ppm). The primary goal of this Monte Carlo (MC) study was to investigate the feasibility of upgrading an existing experimental benchtop XRF/XFCT imaging setup adopting a single silicon drift detector (SDD), developed based on the aforementioned concept (often known as L-shell XFCT), by deploying another SDD within the same setup. Specifically, an MC model of the original single SDD L-shell XFCT setup, …


Proceedings Of The National Cancer Institute Workshop On Combining Immunotherapy With Radiotherapy: Challenges And Opportunities For Clinical Translation, Zachary S Morris, Sandra Demaria, Arta M Monjazeb, Silvia C Formenti, Ralph R Weichselbaum, James Welsh, Heiko Enderling, Jonathan D Schoenfeld, Joshua D Brody, Heather M Mcgee, Michele Mondini, Michael S Kent, Kristina H Young, Lorenzo Galluzzi, Sana D Karam, Willemijn S M E Theelen, Joe Y Chang, Mai Anh Huynh, Adi Daib, Sean Pitroda, Caroline Chung, Raphael Serre, Clemens Grassberger, Jie Deng, Quaovi H Sodji, Anthony T Nguyen, Ravi B Patel, Simone Krebs, Anusha Kalbasi, Caroline Kerr, Claire Vanpouille-Box, Logan Vick, Todd A Aguilera, Irene M Ong, Fernanda Herrera, Hari Menon, Deedee Smart, Jalal Ahmed, Robyn D Gartrell, Christina L Roland, Fatemeh Fekrmandi, Binita Chakraborty, Eric H Bent, Tracy J Berg, Alan Hutson, Samir Khleif, Andrew G Sikora, Lawrence Fong Mar 2025

Proceedings Of The National Cancer Institute Workshop On Combining Immunotherapy With Radiotherapy: Challenges And Opportunities For Clinical Translation, Zachary S Morris, Sandra Demaria, Arta M Monjazeb, Silvia C Formenti, Ralph R Weichselbaum, James Welsh, Heiko Enderling, Jonathan D Schoenfeld, Joshua D Brody, Heather M Mcgee, Michele Mondini, Michael S Kent, Kristina H Young, Lorenzo Galluzzi, Sana D Karam, Willemijn S M E Theelen, Joe Y Chang, Mai Anh Huynh, Adi Daib, Sean Pitroda, Caroline Chung, Raphael Serre, Clemens Grassberger, Jie Deng, Quaovi H Sodji, Anthony T Nguyen, Ravi B Patel, Simone Krebs, Anusha Kalbasi, Caroline Kerr, Claire Vanpouille-Box, Logan Vick, Todd A Aguilera, Irene M Ong, Fernanda Herrera, Hari Menon, Deedee Smart, Jalal Ahmed, Robyn D Gartrell, Christina L Roland, Fatemeh Fekrmandi, Binita Chakraborty, Eric H Bent, Tracy J Berg, Alan Hutson, Samir Khleif, Andrew G Sikora, Lawrence Fong

Faculty, Staff and Student Publications

Radiotherapy both promotes and antagonises tumour immune recognition. Some clinical studies show improved patient outcomes when immunotherapies are integrated with radiotherapy. Safe, greater than additive, clinical response to the combination is limited to a subset of patients, however, and how radiotherapy can best be combined with immunotherapies remains unclear. The National Cancer Institute-Immuno-Oncology Translational Network-Society for Immunotherapy of Cancer-American Association of Immunology Workshop on Combining Immunotherapy with Radiotherapy was convened to identify and prioritise opportunities and challenges for radiotherapy and immunotherapy combinations. Sessions examined the immune effects of radiation, barriers to anti-tumour immune response, previous clinical trial data, immunological and …


Multiethnic Growth Standards For Fetal Body Composition And Organ Volumes Derived From 3d Ultrasonography, Katherine L Grantz, Wesley Lee, Lauren M Mack, Magdalena Sanz Cortes, Luis F Goncalves, Jimmy Espinoza, Roger B Newman, William A Grobman, Ronald J Wapner, Karin Fuchs, Mary E D'Alton, Daniel W Skupski, John Owen, Anthony Sciscione, Deborah A Wing, Michael P Nageotte, Angela C Ranzini, Edward K Chien, Sabrina Craigo, Seth Sherman, Robert E Gore-Langton, Dian He, Fasil Tekola-Ayele, Cuilin Zhang, Jagteshwar Grewal, Zhen Chen Mar 2025

Multiethnic Growth Standards For Fetal Body Composition And Organ Volumes Derived From 3d Ultrasonography, Katherine L Grantz, Wesley Lee, Lauren M Mack, Magdalena Sanz Cortes, Luis F Goncalves, Jimmy Espinoza, Roger B Newman, William A Grobman, Ronald J Wapner, Karin Fuchs, Mary E D'Alton, Daniel W Skupski, John Owen, Anthony Sciscione, Deborah A Wing, Michael P Nageotte, Angela C Ranzini, Edward K Chien, Sabrina Craigo, Seth Sherman, Robert E Gore-Langton, Dian He, Fasil Tekola-Ayele, Cuilin Zhang, Jagteshwar Grewal, Zhen Chen

Faculty, Staff and Student Publications

Background: A major goal of contemporary obstetrical practice is to optimize fetal growth and development throughout pregnancy. To date, fetal growth during prenatal care is assessed by performing ultrasonographic measurement of 2-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established 2-dimensional fetal growth standards using sonographic data from a large cohort with multiple sonograms. A separate objective of that investigation involved the collection of fetal volumes from the same cohort.

Objective: The Fetal 3D Study was designed to establish standards for fetal soft tissue and organ volume measurements by 3-dimensional ultrasonography and compare growth trajectories with …


Intra- And Postoperative Complications In 4565 Vnotes Hysterectomies: International Registry Cohort Study., Andrea Stuart, Johanna Wagenius, Levon Badiglian-Filho, Jens Schnabel, Alvaro Montealegre, Sophia Ehrström, Michael Hartmann, Jona Vercammen, Daniela Huber, Anna Lingström, Jan Baekelandt Mar 2025

Intra- And Postoperative Complications In 4565 Vnotes Hysterectomies: International Registry Cohort Study., Andrea Stuart, Johanna Wagenius, Levon Badiglian-Filho, Jens Schnabel, Alvaro Montealegre, Sophia Ehrström, Michael Hartmann, Jona Vercammen, Daniela Huber, Anna Lingström, Jan Baekelandt

Faculty, Staff and Student Publications

Objective: To present the rates of intra- and postoperative complications and conversions in a large cohort of unselected vNOTES hysterectomies, performed by surgeons with different levels of expertise.

Design: International register-based cohort study.

Setting: Hysterectomies in the iNOTESs registry, 2015 to January 2024, performed by 201 surgeons from multiple countries.

Population: 4565 patients undergoing vNOTES hysterectomy.

Methods: Descriptive data are presented in frequencies (n) and percent (%).

Main outcome measure: Intra- and postoperative complications. Conversions.

Results: Intraoperative and postoperative complication rates were 3.2% (n = 144) and 2.5% (n = 115), respectively. Conversions occurred in 1.6% (n = 72), of …