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Relationship Between C-Reactive Protein/Albumin Ratio And Mucocutaneous Symptom Frequency And Disease Severity In Behçet’S Disease, Erdal Pala, Mustafa Bayraktar Apr 2024

Relationship Between C-Reactive Protein/Albumin Ratio And Mucocutaneous Symptom Frequency And Disease Severity In Behçet’S Disease, Erdal Pala, Mustafa Bayraktar

Turkish Journal of Medical Sciences

Background/aim: There is no specific marker that can be applied to determine the severity of Behçet’s disease. The aim of this study is to investigate the potential of C-reactive protein (CRP)/albumin (CAR) ratio as a tool for assessing the severity of Behçet’s disease.Materials and methods: A retrospective crosssectional study was conducted by examining hospital archives. The CRP and albumin levels of Behçet’s disease patients who presented to our dermatology clinic over a three-year period from February 2020 to February 2022 were included, along with the identical laboratory parameters in the control group. The CAR ratio was calculated and statistically compared …


Swine Influenza A Virus: Challenges And Novel Vaccine Strategies, Erika M. Petro-Turnquist, Matthew J. Pekarek, Eric A. Weaver Apr 2024

Swine Influenza A Virus: Challenges And Novel Vaccine Strategies, Erika M. Petro-Turnquist, Matthew J. Pekarek, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Swine Influenza A Virus (IAV-S) imposes a significant impact on the pork industry and has been deemed a significant threat to global public health due to its zoonotic potential. The most effective method of preventing IAV-S is vaccination. While there are tremendous efforts to control and prevent IAV-S in vulnerable swine populations, there are considerable challenges in developing a broadly protective vaccine against IAV-S. These challenges include the consistent diversification of IAV-S, increasing the strength and breadth of adaptive immune responses elicited by vaccination, interfering maternal antibody responses, and the induction of vaccine-associated enhanced respiratory disease after vaccination. Current vaccination …


Antibody-Mediated Targeting Of Human Microglial Leukocyte Ig-Like Receptor B4 Attenuates Amyloid Pathology In A Mouse Model, Jinchao Hou, Yun Chen, Zhangying Cai, Gyu Seong Heo, Carla M Yuede, Zuoxu Wang, Kent Lin, Fareeha Saadi, Tihana Trsan, Aivi T Nguyen, Eleni Constantopoulos, Rachel A Larsen, Yiyang Zhu, Nicole D Wagner, Nolan Mclaughlin, Xinyi Cynthia Kuang, Alexander D Barrow, Dian Li, Yingyue Zhou, Shoutang Wang, Susan Gilfillan, Michael L Gross, Simone Brioschi, Yongjian Liu, David M Holtzman, Marco Colonna Apr 2024

Antibody-Mediated Targeting Of Human Microglial Leukocyte Ig-Like Receptor B4 Attenuates Amyloid Pathology In A Mouse Model, Jinchao Hou, Yun Chen, Zhangying Cai, Gyu Seong Heo, Carla M Yuede, Zuoxu Wang, Kent Lin, Fareeha Saadi, Tihana Trsan, Aivi T Nguyen, Eleni Constantopoulos, Rachel A Larsen, Yiyang Zhu, Nicole D Wagner, Nolan Mclaughlin, Xinyi Cynthia Kuang, Alexander D Barrow, Dian Li, Yingyue Zhou, Shoutang Wang, Susan Gilfillan, Michael L Gross, Simone Brioschi, Yongjian Liu, David M Holtzman, Marco Colonna

The Brown Foundation: Institute of Molecular Medicine

Microglia help limit the progression of Alzheimer’s disease (AD) by constraining amyloid-β (Aβ) pathology, effected through a balance of activating and inhibitory intracellular signals delivered by distinct cell surface receptors. Human leukocyte Ig-like receptor B4 (LILRB4) is an inhibitory receptor of the immunoglobulin (Ig) superfamily that is expressed on myeloid cells and recognizes apolipoprotein E (ApoE) among other ligands. Here, we find that LILRB4 is highly expressed in microglia of patients with AD. Using mice that accumulate Aβ and carry a transgene encompassing a portion of the LILR region that includes LILRB4, we corroborated abundant LILRB4 expression in microglia …


Oncogenic Oral Human Papillomavirus Clearance Patterns Over 10 Years, Gypsyamber D'Souza, Sakshi R Tewari, Tanya Troy, Jennifer Webster-Cyriaque, Dorothy J Wiley, Cecile Delille Lahiri, Frank Joseph Palella, Maura L Gillison, Howard D Strickler, Linda Struijk, Tim Waterboer, Ken Ho, Jennafer Kwait, Jason Lazar, Kathleen M Weber, Carole Fakhry Apr 2024

Oncogenic Oral Human Papillomavirus Clearance Patterns Over 10 Years, Gypsyamber D'Souza, Sakshi R Tewari, Tanya Troy, Jennifer Webster-Cyriaque, Dorothy J Wiley, Cecile Delille Lahiri, Frank Joseph Palella, Maura L Gillison, Howard D Strickler, Linda Struijk, Tim Waterboer, Ken Ho, Jennafer Kwait, Jason Lazar, Kathleen M Weber, Carole Fakhry

Faculty, Staff and Student Publications

Background: Effective screening for oropharyngeal cancer is lacking. Four oncogenic HPV clearance definitions were explored to understand long-term natural history for persistent oncogenic oral HPV (oncHPV), the precursor of oropharyngeal cancer.

Methods: Prospective multicenter cohort of participants living with/at-risk for HIV, with oral rinse and gargle samples collected every 6 to 12 months for up to 10 years and tested for oncHPV. HPV clearance definitions included 1 (clear1), 2 (clear2), 3 (clear3) consecutive negatives, or being negative at last two visits (clearlast).

Results: Median time to clearance of oncHPV exceeded 2 years for conservative definitions (clear3: 2.38, clearlast: 2.43), but …


Serum And Urine Interferon-Inducible Protein 10, Galectin-9, And Siglec-1 As Biomarkers Of Disease Activity In Systemic Lupus Erythematosus, Şafak Mi̇ri̇oğlu, Suzan Çinar, Ömer Uludağ, Erdem Gürel, Sibel Varelci̇, Yasemin Özlük, Işın Kiliçaslan, Yasemin Yalçinkaya, Halil Yazici, Ahmet Gül, Murat İnanç, Bahar Artim Esen Apr 2024

Serum And Urine Interferon-Inducible Protein 10, Galectin-9, And Siglec-1 As Biomarkers Of Disease Activity In Systemic Lupus Erythematosus, Şafak Mi̇ri̇oğlu, Suzan Çinar, Ömer Uludağ, Erdem Gürel, Sibel Varelci̇, Yasemin Özlük, Işın Kiliçaslan, Yasemin Yalçinkaya, Halil Yazici, Ahmet Gül, Murat İnanç, Bahar Artim Esen

Turkish Journal of Medical Sciences

Background/aim: In this prospective study, we aimed to investigate the association of serum (s) and urine (u) IP-10, galectin-9, and SIGLEC-1 with disease activity in patients with systemic lupus erythematosus (SLE).Materials and methods: Sixty-three patients with active SLE (31 renal, 32 extrarenal) were included. Thirty patients with inactive SLE (15 renal, 15 extrarenal), 17 with renal active AAV, and 32 healthy volunteers were selected as control groups. Serum and urine IP-10, galectin-9, and SIGLEC-1 were tested using ELISA.Results: Levels of sIP-10 (p = 0.046), uIP-10 (p < 0.001), sGalectin-9 (p = 0.03), and uSIGLEC-1 (p = 0.006) were significantly higher in active SLE group compared to the inactive SLE; however, no differences were detected in the comparison of uGalectin-9 (p = 0.18) and sSIGLEC-1 (p = 0.69) between two groups. None of the biomarkers discriminated patients with active renal SLE from active extrarenal SLE. ROC analyses revealed an AUC of 0.63 (0.52–0.73) for sIP-10, 0.78 (0.68–0.86) for uIP-10, 0.64 (0.53–0.74) for sGalectin-9, and 0.68 (0.57–0.77) for uSIGLEC-1 in discriminating disease activity in SLE, which did not outperform C3 (0.75, 0.64–0.84) and C4 (0.72, 0.61–0.82). sIP-10 (p = 0.001), uIP-10 (p = 0.042), and uGalectin-9 (p = 0.009) were significantly increased in patients with active renal SLE compared to active renal AAV. sGalectin-9 (p < 0.001) and sIP-10 levels (p = 0.06) were decreased after 8 (5–22.5) months of treatment.Conclusion: sIP-10, uIP-10, sGalectin-9, and uSIGLEC-1 reflect global disease activity in SLE but do not outperform C3 and C4. sIP-10 and uIP-10 may be specific for active SLE compared to active AAV. sIP-10 and sGalectin-9 might be valuable in monitoring response after treatment.


Antiobesity And Antidyslipidemic Properties Of Clitoria Ternatea Petals Aqueous Extract Against Rats Induced By High-Fat Diet, I Gede Aswin Parisya Sasmana, Desak Made Wihandani, I Gede Krisna Arim Sadeva, Wilson Halim, Putu Putri Agustini, Lalita Samala, I Gusti Ngurah Agung Surya Pratama, Lidiya Nuraliza Rachmawati, Aizar Vesa Prasetyo, Ni Komang Ayu Amanda Setiari Jaya Apr 2024

Antiobesity And Antidyslipidemic Properties Of Clitoria Ternatea Petals Aqueous Extract Against Rats Induced By High-Fat Diet, I Gede Aswin Parisya Sasmana, Desak Made Wihandani, I Gede Krisna Arim Sadeva, Wilson Halim, Putu Putri Agustini, Lalita Samala, I Gusti Ngurah Agung Surya Pratama, Lidiya Nuraliza Rachmawati, Aizar Vesa Prasetyo, Ni Komang Ayu Amanda Setiari Jaya

Turkish Journal of Medical Sciences

Background/aim: Obesity is a chronic metabolic disease involving dysregulation of fat metabolism that affects 13% of the world’s population. Obesity has been linked to dyslipidemia with a lot of complication, including stroke, chronic kidney disease, fatty liver disease, and so on. One of the natural resources that have several potential effects including anticholesterol, antiobesity, and antidyslipidemia is the butterfly pea (Clitoria ternatea/CT). CT’s petal has been found to contain high levels of anthocyanins and tannins that can inhibit the biosynthesis of cholesterol and lipid. This study aims to investigate the antiobesity and antidyslipidemic effects of Clitoria ternatea extract (CTE).Materials and …


Small Airway Resistance In Obese And Nonobese Patients With Obstructive Sleep Apnea Syndrome Using Impulse Oscillometry, Nejdiye Güngördü, Aytan İsmayi̇lova, Nigar Ali̇yeva, Tamer A M Alhelou, Ayşenur Özdi̇l Eser, Ilgım Vardaloğlu Koyuncu, Nihal Enşen, Ersan Atahan, Şermin Börekçi̇, Bilun Gemi̇ci̇oğlu Apr 2024

Small Airway Resistance In Obese And Nonobese Patients With Obstructive Sleep Apnea Syndrome Using Impulse Oscillometry, Nejdiye Güngördü, Aytan İsmayi̇lova, Nigar Ali̇yeva, Tamer A M Alhelou, Ayşenur Özdi̇l Eser, Ilgım Vardaloğlu Koyuncu, Nihal Enşen, Ersan Atahan, Şermin Börekçi̇, Bilun Gemi̇ci̇oğlu

Turkish Journal of Medical Sciences

Background/aim: There is limited information on the pathologic changes in the small airways among obese and nonobese patients with obstructive sleep apnea syndrome (OSAS). Impulse oscillometry (IOS) measures airway resistance and reactance independently of patient effort. This study aimed to compare airway resistance in small airways using IOS between obese and nonobese patients with OSAS.Materials and methods: In this real-life cross-sectional study, demographic information was collected from obese and nonobese subjects diagnosed with moderate and severe OSAS without any other underlying diseases. Spirometry and IOS measurements were conducted, and the values of both groups were statistically analyzed.Results: The nonobese group …


The Effect Of Human Recombinant Epidermal Growth Factor On Neovascularization And Pedicle Division Time In A Rat Interpolation Flap Model, Aziz Parspanci, Yavuz Keçeci̇, Peyker Temi̇z Apr 2024

The Effect Of Human Recombinant Epidermal Growth Factor On Neovascularization And Pedicle Division Time In A Rat Interpolation Flap Model, Aziz Parspanci, Yavuz Keçeci̇, Peyker Temi̇z

Turkish Journal of Medical Sciences

Background/aim: In practice, waiting 2–3 weeks for interpolation flaps pedicle division result in certain morbidities and discomfort for patient. The division time of flap pedicle depends on neovascularization from the recipient bed and includes wound healing stages. We aimed to investigate the effect of recombinant human epidermal growth factor (rhEGF) on the flap viability during early pedicle division.Materials and methods: Thirty-six rats were allocated to two main groups as control and study. A cranial based flap measuring 5 × 5 cm was elevated from the back, including all layers of the skin. While the cranial half of the defect was …


Artificial Intelligence Predictive Analytics In Heart Failure: Results Of The Pilot Phase Of A Pragmatic Randomized Clinical Trial, Konstantinos Sideris, Charlene R Weir, Carsten Schmalfuss, Heather Hanson, Matt Pipke, Po-He Tseng, Neil Lewis, Karim Sallam, Biykem Bozkurt, Thomas Hanff, Richard Schofield, Karen Larimer, Christos P Kyriakopoulos, Iosif Taleb, Lina Brinker, Tempa Curry, Cheri Knecht, Jorie M Butler, Josef Stehlik Apr 2024

Artificial Intelligence Predictive Analytics In Heart Failure: Results Of The Pilot Phase Of A Pragmatic Randomized Clinical Trial, Konstantinos Sideris, Charlene R Weir, Carsten Schmalfuss, Heather Hanson, Matt Pipke, Po-He Tseng, Neil Lewis, Karim Sallam, Biykem Bozkurt, Thomas Hanff, Richard Schofield, Karen Larimer, Christos P Kyriakopoulos, Iosif Taleb, Lina Brinker, Tempa Curry, Cheri Knecht, Jorie M Butler, Josef Stehlik

Faculty, Staff and Students Publications

OBJECTIVES: We conducted an implementation planning process during the pilot phase of a pragmatic trial, which tests an intervention guided by artificial intelligence (AI) analytics sourced from noninvasive monitoring data in heart failure patients (LINK-HF2).

MATERIALS AND METHODS: A mixed-method analysis was conducted at 2 pilot sites. Interviews were conducted with 12 of 27 enrolled patients and with 13 participating clinicians. iPARIHS constructs were used for interview construction to identify workflow, communication patterns, and clinician's beliefs. Interviews were transcribed and analyzed using inductive coding protocols to identify key themes. Behavioral response data from the AI-generated notifications were collected.

RESULTS: Clinicians …


Gabaergic/Glycinergic And Glutamatergic Neurons Mediate Distinct Neurodevelopmental Phenotypes Of Stxbp1 Encephalopathy, Joo Hyun Kim, Wu Chen, Eugene S Chao, Armando Rivera, Heet Naresh Kaku, Kevin Jiang, Dongwon Lee, Hongmei Chen, Jaimie M Vega, Teresa V Chin, Kevin Jin, Kelly T Nguyen, Sheldon S Zou, Zain Moin, Shawn Nguyen, Mingshan Xue 薛名杉 Apr 2024

Gabaergic/Glycinergic And Glutamatergic Neurons Mediate Distinct Neurodevelopmental Phenotypes Of Stxbp1 Encephalopathy, Joo Hyun Kim, Wu Chen, Eugene S Chao, Armando Rivera, Heet Naresh Kaku, Kevin Jiang, Dongwon Lee, Hongmei Chen, Jaimie M Vega, Teresa V Chin, Kevin Jin, Kelly T Nguyen, Sheldon S Zou, Zain Moin, Shawn Nguyen, Mingshan Xue 薛名杉

Faculty, Staff and Students Publications

An increasing number of pathogenic variants in presynaptic proteins involved in the synaptic vesicle cycle are being discovered in neurodevelopmental disorders. The clinical features of these synaptic vesicle cycle disorders are diverse, but the most prevalent phenotypes include intellectual disability, epilepsy, movement disorders, cerebral visual impairment, and psychiatric symptoms ( Verhage and Sørensen, 2020; Bonnycastle et al., 2021; John et al., 2021; Melland et al., 2021). Among this growing list of synaptic vesicle cycle disorders, the most frequent is STXBP1 encephalopathy caused by de novo heterozygous pathogenic variants in syntaxin-binding protein 1 (STXBP1, also known as …


Ai Is A Viable Alternative To High Throughput Screening: A 318-Target Study, Izhar Wallach, Denzil Bernard, Kong Nguyen, Gregory Ho, Adrian Morrison, Adrian Stecula, Andreana Rosnik, Ann Marie O’Sullivan, Aram Davtyan, Ben Samudio, Bill Thomas, Brad Worley, Brittany Butler, Christian Laggner, Desiree Thayer, Ehsan Moharreri, Greg Friedland, Ha Truong, Henry Van Den Bedem, Ho Leung Ng, Kate Stafford, Krishna Sarangapani, Kyle Giesler, Lien Ngo, Michael Mysinger, Mostafa Ahmed, Nicholas J. Anthis, Niel Henriksen, Arthur L. Haas, Et Al Apr 2024

Ai Is A Viable Alternative To High Throughput Screening: A 318-Target Study, Izhar Wallach, Denzil Bernard, Kong Nguyen, Gregory Ho, Adrian Morrison, Adrian Stecula, Andreana Rosnik, Ann Marie O’Sullivan, Aram Davtyan, Ben Samudio, Bill Thomas, Brad Worley, Brittany Butler, Christian Laggner, Desiree Thayer, Ehsan Moharreri, Greg Friedland, Ha Truong, Henry Van Den Bedem, Ho Leung Ng, Kate Stafford, Krishna Sarangapani, Kyle Giesler, Lien Ngo, Michael Mysinger, Mostafa Ahmed, Nicholas J. Anthis, Niel Henriksen, Arthur L. Haas, Et Al

School of Medicine Faculty Publications

High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, …


Identification Of Colorectal Cancer Cell Stemness From Single-Cell Rna Sequencing, Kangyu Lin, Saikat Chowdhury, Mohammad A Zeineddine, Fadl A Zeineddine, Nicholas J Hornstein, Oscar E Villarreal, Dipen M Maru, Cara L Haymaker, Jean-Nicolas Vauthey, George J Chang, Elena Bogatenkova, David Menter, Scott Kopetz, John Paul Shen Apr 2024

Identification Of Colorectal Cancer Cell Stemness From Single-Cell Rna Sequencing, Kangyu Lin, Saikat Chowdhury, Mohammad A Zeineddine, Fadl A Zeineddine, Nicholas J Hornstein, Oscar E Villarreal, Dipen M Maru, Cara L Haymaker, Jean-Nicolas Vauthey, George J Chang, Elena Bogatenkova, David Menter, Scott Kopetz, John Paul Shen

Faculty, Staff and Student Publications

UNLABELLED: Cancer stem cells (CSC) play a critical role in metastasis, relapse, and therapy resistance in colorectal cancer. While characterization of the normal lineage of cell development in the intestine has led to the identification of many genes involved in the induction and maintenance of pluripotency, recent studies suggest significant heterogeneity in CSC populations. Moreover, while many canonical colorectal cancer CSC marker genes have been identified, the ability to use these classical markers to annotate stemness at the single-cell level is limited. In this study, we performed single-cell RNA sequencing on a cohort of 6 primary colon, 9 liver metastatic …


Neutrophil Elastase Remodels Mammary Tumors To Facilitate Lung Metastasis, Amriti R Lulla, Said Akli, Cansu Karakas, Joseph A Caruso, Lucas D Warma, Natalie W Fowlkes, Xiayu Rao, Jing Wang, Kelly K Hunt, Stephanie S Watowich, Khandan Keyomarsi Apr 2024

Neutrophil Elastase Remodels Mammary Tumors To Facilitate Lung Metastasis, Amriti R Lulla, Said Akli, Cansu Karakas, Joseph A Caruso, Lucas D Warma, Natalie W Fowlkes, Xiayu Rao, Jing Wang, Kelly K Hunt, Stephanie S Watowich, Khandan Keyomarsi

Faculty, Staff and Student Publications

Metastatic disease remains the leading cause of death due to cancer, yet the mechanism(s) of metastasis and its timely detection remain to be elucidated. Neutrophil elastase (NE), a serine protease secreted by neutrophils, is a crucial mediator of chronic inflammation and tumor progression. In this study, we used the PyMT model (NE+/+ and NE-/-) of breast cancer to interrogate the tumor-intrinsic and -extrinsic mechanisms by which NE can promote metastasis. Our results showed that genetic ablation of NE significantly reduced lung metastasis and improved metastasis-free survival. RNA-sequencing analysis of primary tumors indicated differential regulation of tumor-intrinsic actin cytoskeleton signaling pathways …


Genetic Ancestry And Radical Prostatectomy Findings In Hispanic/Latino Patients, Natalia L. Acosta-Vega, Rodolfo Varela, Jorge Andrés Mesa, Jone Garai, Alberto Gómez-Gutiérrez, Silvia J. Serrano-Gómez, Jovanny Zabaleta, María Carolina Sanabria-Salas, Alba L. Combita Apr 2024

Genetic Ancestry And Radical Prostatectomy Findings In Hispanic/Latino Patients, Natalia L. Acosta-Vega, Rodolfo Varela, Jorge Andrés Mesa, Jone Garai, Alberto Gómez-Gutiérrez, Silvia J. Serrano-Gómez, Jovanny Zabaleta, María Carolina Sanabria-Salas, Alba L. Combita

School of Medicine Faculty Publications

Background: African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia. Patients and methods: We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry …


Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission By Promoting B/Cd 4 T Cell Crosstalk, Chengyi Li, Ryan Clauson, Luke F Bugada, Fang Ke, Bing He, Zhixin Yu, Hongwei Chen, Binyamin Jacobovitz, Hongxiang Hu, Polina Chuikov, Brett Dallas Hill, Syed M Rizvi, Yudong Song, Kai Sun, Pasieka Axenov, Daniel Huynh, Xinyi Wang, Lana Garmire, Yu Leo Lei, Irina Grigorova, Fei Wen, Marilia Cascalho, Wei Gao, Duxin Sun Apr 2024

Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission By Promoting B/Cd 4 T Cell Crosstalk, Chengyi Li, Ryan Clauson, Luke F Bugada, Fang Ke, Bing He, Zhixin Yu, Hongwei Chen, Binyamin Jacobovitz, Hongxiang Hu, Polina Chuikov, Brett Dallas Hill, Syed M Rizvi, Yudong Song, Kai Sun, Pasieka Axenov, Daniel Huynh, Xinyi Wang, Lana Garmire, Yu Leo Lei, Irina Grigorova, Fei Wen, Marilia Cascalho, Wei Gao, Duxin Sun

Faculty, Staff and Student Publications

Current cancer vaccines using T cell epitopes activate antitumor T cell immunity through dendritic cell/macrophage-mediated antigen presentation, but they lack the ability to promote B/CD4 T cell crosstalk, limiting their anticancer efficacy. We developed antigen-clustered nanovaccine (ACNVax) to achieve long-term tumor remission by promoting B/CD4 T cell crosstalk. The topographic features of ACNVax were achieved using an iron nanoparticle core attached with an optimal number of gold nanoparticles, where the clusters of HER2 B/CD4 T cell epitopes were conjugated on the gold surface with an optimal intercluster distance of 5-10 nm. ACNVax effectively trafficked to lymph nodes and cross-linked with …


Targeting Branched N-Glycans And Fucosylation Sensitizes Ovarian Tumors To Immune Checkpoint Blockade, Hao Nie, Pratima Saini, Taito Miyamoto, Liping Liao, Rafal J Zielinski, Heng Liu, Wei Zhou, Chen Wang, Brennah Murphy, Martina Towers, Tyler Yang, Yuan Qi, Toshitha Kannan, Andrew Kossenkov, Hiroaki Tateno, Daniel T Claiborne, Nan Zhang, Mohamed Abdel-Mohsen, Rugang Zhang Apr 2024

Targeting Branched N-Glycans And Fucosylation Sensitizes Ovarian Tumors To Immune Checkpoint Blockade, Hao Nie, Pratima Saini, Taito Miyamoto, Liping Liao, Rafal J Zielinski, Heng Liu, Wei Zhou, Chen Wang, Brennah Murphy, Martina Towers, Tyler Yang, Yuan Qi, Toshitha Kannan, Andrew Kossenkov, Hiroaki Tateno, Daniel T Claiborne, Nan Zhang, Mohamed Abdel-Mohsen, Rugang Zhang

Faculty, Staff and Student Publications

Aberrant glycosylation is a crucial strategy employed by cancer cells to evade cellular immunity. However, it's unclear whether homologous recombination (HR) status-dependent glycosylation can be therapeutically explored. Here, we show that the inhibition of branched N-glycans sensitizes HR-proficient, but not HR-deficient, epithelial ovarian cancers (EOCs) to immune checkpoint blockade (ICB). In contrast to fucosylation whose inhibition sensitizes EOCs to anti-PD-L1 immunotherapy regardless of HR-status, we observe an enrichment of branched N-glycans on HR-proficient compared to HR-deficient EOCs. Mechanistically, BRCA1/2 transcriptionally promotes the expression of MGAT5, the enzyme responsible for catalyzing branched N-glycans. The branched N-glycans on HR-proficient tumors augment their …


Ai Is A Viable Alternative To High Throughput Screening: A 318-Target Study, The Atomwise Aims Program Apr 2024

Ai Is A Viable Alternative To High Throughput Screening: A 318-Target Study, The Atomwise Aims Program

Faculty, Staff and Student Publications

High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, …


Early Screening Of Colorectal Cancer Using Feature Engineering With Artificial Intelligence-Enhanced Analysis Of Nanoscale Chromatin Modifications, Andrew Chang, Sravya Prabhala, Ali Daneshkhah, Jianan Lin, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman Apr 2024

Early Screening Of Colorectal Cancer Using Feature Engineering With Artificial Intelligence-Enhanced Analysis Of Nanoscale Chromatin Modifications, Andrew Chang, Sravya Prabhala, Ali Daneshkhah, Jianan Lin, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman

Faculty, Staff and Students Publications

Colonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~ 7 to 8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~ 5 to 20 nm, ~1 kbp) fold into chromatin packing domains (~ 100 to 200 nm, ~ 100 to 1000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity …


Hedgehog Signaling And Congenital Disorders; The Case Of Anencephaly And Polydactyly, Joshua Towery Apr 2024

Hedgehog Signaling And Congenital Disorders; The Case Of Anencephaly And Polydactyly, Joshua Towery

First-Year Research Immersion (FRI) Scholarship

The Hedgehog pathway is a fundamental signaling pathway in the human body; involved in carcinogenesis, stem cell maintenance, as well as limb patterning in embryonic development. Originally discovered in drosophila, their initial discovery, and subsequent analysis revealed many novel pieces of information about the mechanisms inside the human body, as many core components of the signaling pathway are carried over from fruit flies to humans. Because of the key roles hedgehog signaling plays in human development, dysfunction and mutations in the pathway can be detrimental. This review will focus on two congenital birth defects thought to be caused by hedgehog …


Storytelling Heals The Wounded Mind, Liliana Whitaker Apr 2024

Storytelling Heals The Wounded Mind, Liliana Whitaker

Classical Conversations

Humans are storytelling creatures. We use stories to communicate ideas in a memorable and engaging way, inspire people to believe in the best version of themselves, find truth in our legal system, empathize with experiences different than our own, and entertain ourselves for hours on end. Recent neuroscience proposes that the human mind thinks through stories. Narrative is the technical and broad term for story, defined as a series of actions and events that unfold over time according to proper cause and effect. Narrative practice is an emerging field comprising of storytelling treatments in therapy and medicine, usually focusing on …


Genetic Analysis Of Hereditary Gingival Fibromatosis Associated Sos1 Missense Variants Of Uncertain Significance In Caenorhabditis Elegans, Himani Patel Apr 2024

Genetic Analysis Of Hereditary Gingival Fibromatosis Associated Sos1 Missense Variants Of Uncertain Significance In Caenorhabditis Elegans, Himani Patel

Theses

Hereditary gingival fibromatosis (HGF) is a disease that can present as benign overgrowth of gingival tissue in the mouth. The overgrowth can enclose the entire mouth and teeth in severe cases or present itself in a concentrated area. Researchers have identified that mutations in the SOS1 gene can be responsible for HGF. This disease can impair basic functions related to the mouth. Eating, smiling, speaking can all be affected. Additionally, excess inflammation can cause periodontal disease because of the difficulty in maintaining proper oral health. Periodontal disease can lead to severe bone loss which can lead to complete loss of …


Analyzing Pelvic Asymmetry By Sex And Ancestry: Insights From An Osteological Collection, Bryan O Ren, Robert W Goldberg, Karen D Standefer, Jason R Teplensky, Joseph P Drain, Conor F Mccarthy, John G Birch, Raymond W Liu Apr 2024

Analyzing Pelvic Asymmetry By Sex And Ancestry: Insights From An Osteological Collection, Bryan O Ren, Robert W Goldberg, Karen D Standefer, Jason R Teplensky, Joseph P Drain, Conor F Mccarthy, John G Birch, Raymond W Liu

Faculty, Staff and Student Publications

Introduction: Pelvic asymmetry has been noted in pelvic imaging, and might influence the development of various spinal pathologies, most notably scoliosis. There is a limited understanding of the relationship between pelvic asymmetry and sex and ancestry, and limited use of 3D modeling. The purpose of this study was to identify pelvic asymmetry and morphology differences between sex and ancestry utilizing 3D modeling on young adults in an osteological collection.

Methods: Thirty-three osteological pelvic specimens aged 18-25 years (average age 21.4 ± 2.0 years) were scanned to create virtual 3D models for analysis. Pelvic asymmetry and morphology were measured and compared …


Dean's Report-Spring 2024, Marina K. Holz Apr 2024

Dean's Report-Spring 2024, Marina K. Holz

GSBMS Dean’s Report

No abstract provided.


Longitudinal Evaluation Of Vitamin D Concentrations In Relation To The Onset Of Type 2 Diabetes In American Adults: A Secondary Data Analysis, Kathryn Michelle Schurr Apr 2024

Longitudinal Evaluation Of Vitamin D Concentrations In Relation To The Onset Of Type 2 Diabetes In American Adults: A Secondary Data Analysis, Kathryn Michelle Schurr

Dissertations

Background: Prior research has suggested that low levels of Vitamin D may have negative effects on various biological functions, including Type 2 diabetes. The relationship between Vitamin D and the risk of Type 2 Diabetes has not yet been fully investigated. The objective of this research is to examine patients’ laboratory test data longitudinally to determine how vitamin D and other covariates of interest affect Type 2 diabetes status over time.

Methods: This study used retrospective data review from Quest Diagnostics from January 1, 2010, through December 31, 2022. Patients included in the study were required to have consecutive test …


Dean's Update, April 2024, Neil W. Schluger Apr 2024

Dean's Update, April 2024, Neil W. Schluger

SOM Dean's Research Newsletter

No abstract provided.


The Influence Of Cards Toxin In Abetting The Virulence Of Mycoplasma Pneumoniae, Layla Abdulbaki Apr 2024

The Influence Of Cards Toxin In Abetting The Virulence Of Mycoplasma Pneumoniae, Layla Abdulbaki

Posters - 2024

Mycoplasma pneumonia is a human bacterial pathogen known to induce chronic upper and lower respiratory infections. This bacterium commonly causes acute, chronic infections, such as atypical pneumonia, and spreads through droplet transmission (> 5 microns). M. pneumoniae damages cells by attacking the epithelium of the respiratory tract, resulting in epithelium shedding. Infection of the airway tract by M. pneumoniae will usually express itself in people with chronic symptoms such as coughing, dyspnea, diarrhea, and epiphora. With this being said, this bacterium is ambit, meaning that it is versatile in who it affects (children to adults), how it manifests (pneumonia, tracheobronchitis, …


Eaat4-Dependent Effects On Glutamatergic Signaling In The Cerebellar Molecular Layer, Christopher Chen Apr 2024

Eaat4-Dependent Effects On Glutamatergic Signaling In The Cerebellar Molecular Layer, Christopher Chen

Dissertations (1934 -)

Glutamatergic signaling is fundamental to human behavior and its dysfunction is implicated in a wide range of neurological and neurodegenerative disorders. Excitatory amino-acid transporters (EAATs) – of which four primary subtypes (EAAT1, EAAT2, EAAT3, and EAAT4) exist in the human brain – are primary regulators of glutamate signaling. Endogenously-expressed at either low (EAAT4-low) or high (EAAT4-high) concentration in cerebellar Purkinje cells, EAAT4 has been shown to regulate Purkinje cell activity in the cerebellar molecular layer. However, differences in glutamatergic signaling at the circuit and single-synaptic levels in EAAT4-low and EAAT4-high regions are poorly understood. To characterize EAAT4-specific effects on excitatory …


2024 Research Day Program, Lincoln Memorial University Apr 2024

2024 Research Day Program, Lincoln Memorial University

Research Day

This program contains abstracts and presentation summaries from LMU's 2024 Annual Research Day conference.


Population Coding Of Strategic Variables During Foraging In Freely Moving Macaques, Neda Shahidi, Melissa Franch, Arun Parajuli, Paul Schrater, Anthony Wright, Xaq Pitkow, Valentin Dragoi Apr 2024

Population Coding Of Strategic Variables During Foraging In Freely Moving Macaques, Neda Shahidi, Melissa Franch, Arun Parajuli, Paul Schrater, Anthony Wright, Xaq Pitkow, Valentin Dragoi

Faculty, Staff and Student Publications

Until now, it has been difficult to examine the neural bases of foraging in naturalistic environments because previous approaches have relied on restrained animals performing trial-based foraging tasks. Here we allowed unrestrained monkeys to freely interact with concurrent reward options while we wirelessly recorded population activity in the dorsolateral prefrontal cortex. The animals decided when and where to forage based on whether their prediction of reward was fulfilled or violated. This prediction was not solely based on a history of reward delivery, but also on the understanding that waiting longer improves the chance of reward. The task variables were continuously …


Comprehensive Analysis Of Transcription Factor-Based Molecular Subtypes And Their Correlation To Clinical Outcomes In Small-Cell Lung Cancer, Sehhoon Park, Tae Hee Hong, Soohyun Hwang, Simon Heeke, Carl M Gay, Jiyeon Kim, Hyun-Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Jong Ho Cho, Yong Soo Choi, Jhingook Kim, Young Mog Shim, Hong Kwan Kim, Lauren Averett Byers, John V Heymach, Yoon-La Choi, Se-Hoon Lee, Keunchil Park Apr 2024

Comprehensive Analysis Of Transcription Factor-Based Molecular Subtypes And Their Correlation To Clinical Outcomes In Small-Cell Lung Cancer, Sehhoon Park, Tae Hee Hong, Soohyun Hwang, Simon Heeke, Carl M Gay, Jiyeon Kim, Hyun-Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Jong Ho Cho, Yong Soo Choi, Jhingook Kim, Young Mog Shim, Hong Kwan Kim, Lauren Averett Byers, John V Heymach, Yoon-La Choi, Se-Hoon Lee, Keunchil Park

Faculty, Staff and Student Publications

BACKGROUND: Recent studies have reported the predictive and prognostic value of novel transcriptional factor-based molecular subtypes in small-cell lung cancer (SCLC). We conducted an in-depth analysis pairing multi-omics data with immunohistochemistry (IHC) to elucidate the underlying characteristics associated with differences in clinical outcomes between subtypes.

METHODS: IHC (n = 252), target exome sequencing (n = 422), and whole transcriptome sequencing (WTS, n = 189) data generated from 427 patients (86.4% males, 13.6% females) with SCLC were comprehensively analysed. The differences in the mutation profile, gene expression profile, and inflammed signatures were analysed according to the IHC-based molecular subtype.

FINDINGS: IHC-based …