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Full-Text Articles in Medical Specialties

Recombinant Protein Micelles To Block Transduction By Sars-Cov-2 Pseudovirus, Rajarshi Chattaraj, Christina Y Kim, Daeyeon Lee, Daniel A Hammer Oct 2022

Recombinant Protein Micelles To Block Transduction By Sars-Cov-2 Pseudovirus, Rajarshi Chattaraj, Christina Y Kim, Daeyeon Lee, Daniel A Hammer

Faculty, Staff and Student Publications

The continuing emergence of variants of the SARS-CoV-2 virus requires the development of modular molecular therapies. Here, we engineered a recombinant amphiphilic protein, oleosin, to spontaneously self-assemble into multivalent micellar nanostructures which can block the Spike S1 protein of SARS-CoV-2 pseudoviruses (PVs). Short recombinant proteins like oleosin can be formulated more easily than antibodies and can be functionalized with precision through genetic engineering. We cloned S1-binding mini-protein genes called LCB


Biomarkers Beyond Brca: Promising Combinatorial Treatment Strategies In Overcoming Resistance To Parp Inhibitors, Yu-Yi Chu, Clinton Yam, Hirohito Yamaguchi, Mien-Chie Hung Oct 2022

Biomarkers Beyond Brca: Promising Combinatorial Treatment Strategies In Overcoming Resistance To Parp Inhibitors, Yu-Yi Chu, Clinton Yam, Hirohito Yamaguchi, Mien-Chie Hung

Faculty, Staff and Student Publications

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) exploit the concept of synthetic lethality and offer great promise in the treatment of tumors with deficiencies in homologous recombination (HR) repair. PARPi exert antitumor activity by blocking Poly(ADP-ribosyl)ation (PARylation) and trapping PARP1 on damaged DNA. To date, the U.S. Food and Drug Administration (FDA) has approved four PARPi for the treatment of several cancer types including ovarian, breast, pancreatic and prostate cancer. Although patients with HR-deficient tumors benefit from PARPi, majority of tumors ultimately develop acquired resistance to PARPi. Furthermore, even though BRCA1/2 mutations are commonly used as markers of PARPi sensitivity in …


Summit: An Integrative Approach For Better Transcriptomic Data Imputation Improves Causal Gene Identification, Zichen Zhang, Ye Eun Bae, Jonathan R Bradley, Lang Wu, Chong Wu Oct 2022

Summit: An Integrative Approach For Better Transcriptomic Data Imputation Improves Causal Gene Identification, Zichen Zhang, Ye Eun Bae, Jonathan R Bradley, Lang Wu, Chong Wu

Faculty, Staff and Student Publications

Genes with moderate to low expression heritability may explain a large proportion of complex trait etiology, but such genes cannot be sufficiently captured in conventional transcriptome-wide association studies (TWASs), partly due to the relatively small available reference datasets for developing expression genetic prediction models to capture the moderate to low genetically regulated components of gene expression. Here, we introduce a method, the Summary-level Unified Method for Modeling Integrated Transcriptome (SUMMIT), to improve the expression prediction model accuracy and the power of TWAS by using a large expression quantitative trait loci (eQTL) summary-level dataset. We apply SUMMIT to the eQTL summary-level …


Prevalence Of Prediabetes And Diabetes Vary By Ethnicity Among Us Asian Adults At Healthy Weight, Overweight, And Obesity Ranges: An Electronic Health Record Study, William S Vicks, Joan C Lo, Lynn Guo, Jamal S Rana, Sherry Zhang, Nirmala D Ramalingam, Nancy P Gordon Oct 2022

Prevalence Of Prediabetes And Diabetes Vary By Ethnicity Among Us Asian Adults At Healthy Weight, Overweight, And Obesity Ranges: An Electronic Health Record Study, William S Vicks, Joan C Lo, Lynn Guo, Jamal S Rana, Sherry Zhang, Nirmala D Ramalingam, Nancy P Gordon

Faculty, Staff and Student Publications

BACKGROUND: Asian adults develop Type 2 diabetes at a lower body mass index (BMI) compared to other racial/ethnic groups. We examined the variation in prevalence of prediabetes and diabetes among Asian ethnic groups within weight strata by comparing middle-aged Chinese, Filipino, South Asian, and White adults receiving care in the same integrated healthcare delivery system.

METHODS: Our retrospective cross-sectional U.S. study examined data from 283,110 (non-Hispanic) White, 33,263 Chinese, 38,766 Filipino, and 17,959 South Asian adults aged 45-64 years who were members of a Northern California health plan in 2016 and had measured height and weight. Prediabetes and diabetes were …


Growth Differentiation Factor 15 Is Not Associated With Glycemic Control In Patients With Type 2 Diabetes Mellitus Treated With Metformin: A Post-Hoc Analysis Of Aim Study, Fei Gao, Cheng Li, Yufei Wang, Jingyi Lu, Wei Lu, Jian Zhou, Jun Yin, Xiaojing Ma Oct 2022

Growth Differentiation Factor 15 Is Not Associated With Glycemic Control In Patients With Type 2 Diabetes Mellitus Treated With Metformin: A Post-Hoc Analysis Of Aim Study, Fei Gao, Cheng Li, Yufei Wang, Jingyi Lu, Wei Lu, Jian Zhou, Jun Yin, Xiaojing Ma

Faculty, Staff and Student Publications

BACKGROUND: Growth differentiation factor 15 (GDF15) was newly discovered to be a promising target of metformin. The study was aimed to investigate the relationship between GDF15 and glycemic control after metformin treatment in patients with type 2 diabetes mellitus.

METHODS: The study was a post-hoc analysis of AIM (the effect of Acarbose on glycemic variability in patients with type 2 diabetes mellitus using premixed Insulin compared to Metformin) study. The participants were randomly assigned to 12 weeks of metformin (MET) or acarbose (ACA) treatment combined with insulin. Serum GDF15 levels of 51 subjects from MET group and 53 subjects from …


Interactions Between Environmental Factors And Glutathione S-Transferase (Gst) Genes With Respect To Detectable Blood Aluminum Concentrations In Jamaican Children, Mohammad H Rahbar, Maureen Samms-Vaughan, Yuansong Zhao, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare-Pellington, Katherine A Loveland Oct 2022

Interactions Between Environmental Factors And Glutathione S-Transferase (Gst) Genes With Respect To Detectable Blood Aluminum Concentrations In Jamaican Children, Mohammad H Rahbar, Maureen Samms-Vaughan, Yuansong Zhao, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare-Pellington, Katherine A Loveland

Faculty, Staff and Student Publications

Aluminum (Al) is a metallic toxicant at high concentrations following natural or unnatural exposures. Dietary intake is considered as the main source of aluminum exposure in children. We used data from 366 typically developing (TD) children (ages 2−8 years) who participated as controls in an age- and sex-matched case−control study in Jamaica. We investigated additive and interactive associations among environmental factors and children’s genotypes for glutathione S-transferase (GST) genes (GSTT1, GSTM1, GSTP1), in relation to having a detectable blood aluminum concentration (BAlC) of >5.0 μg/L, using multivariable logistic regression models. Findings from interactive models revealed that the odds of having …


Lenalidomide Promotes The Development Of Tp53-Mutated Therapy-Related Myeloid Neoplasms, Adam S Sperling, Veronica A Guerra, James A Kennedy, Yuanqing Yan, Joanne I Hsu, Feng Wang, Andrew T Nguyen, Peter G Miller, Marie E Mcconkey, Vanessa A Quevedo Barrios, Ken Furudate, Linda Zhang, Rashmi Kanagal-Shamanna, Jianhua Zhang, Latasha Little, Curtis Gumbs, Naval Daver, Courtney D Dinardo, Tapan Kadia, Farhad Ravandi, Hagop Kantarjian, Guillermo Garcia-Manero, P Andrew Futreal, Benjamin L Ebert, Koichi Takahashi Oct 2022

Lenalidomide Promotes The Development Of Tp53-Mutated Therapy-Related Myeloid Neoplasms, Adam S Sperling, Veronica A Guerra, James A Kennedy, Yuanqing Yan, Joanne I Hsu, Feng Wang, Andrew T Nguyen, Peter G Miller, Marie E Mcconkey, Vanessa A Quevedo Barrios, Ken Furudate, Linda Zhang, Rashmi Kanagal-Shamanna, Jianhua Zhang, Latasha Little, Curtis Gumbs, Naval Daver, Courtney D Dinardo, Tapan Kadia, Farhad Ravandi, Hagop Kantarjian, Guillermo Garcia-Manero, P Andrew Futreal, Benjamin L Ebert, Koichi Takahashi

Faculty, Staff and Student Publications

There is a growing body of evidence that therapy-related myeloid neoplasms (t-MNs) with driver gene mutations arise in the background of clonal hematopoiesis (CH) under the positive selective pressure of chemo- and radiation therapies. Uncovering the exposure relationships that provide selective advantage to specific CH mutations is critical to understanding the pathogenesis and etiology of t-MNs. In a systematic analysis of 416 patients with t-MN and detailed prior exposure history, we found that TP53 mutations were significantly associated with prior treatment with thalidomide analogs, specifically lenalidomide. We demonstrated experimentally that lenalidomide treatment provides a selective advantage to Trp53-mutant hematopoietic stem …


Detection Of Fibular Rotational Changes In Cone Beam Ct: Experimental Study In A Specimen Model, Nils Beisemann, Antonella M Tilk, Jula Gierse, Paul A Grützner, Jochen Franke, Jeffrey H Siewerdsen, Sven Y Vetter Oct 2022

Detection Of Fibular Rotational Changes In Cone Beam Ct: Experimental Study In A Specimen Model, Nils Beisemann, Antonella M Tilk, Jula Gierse, Paul A Grützner, Jochen Franke, Jeffrey H Siewerdsen, Sven Y Vetter

Faculty, Staff and Student Publications

BACKGROUND: In syndesmotic injuries, incorrect reduction leads to early arthrosis of the ankle joint. Being able to analyze the reduction result is therefore crucial for obtaining an anatomical reduction. Several studies that assess fibular rotation in the incisura have already been published. The aim of the study was to validate measurement methods that use cone beam computed tomography imaging to detect rotational malpositions of the fibula in a standardized specimen model.

METHODS: An artificial Maisonneuve injury was created on 16 pairs of fresh-frozen lower legs. Using a stable instrument, rotational malpositions of 5, 10, and 15° internal and external rotation …


Recent Advances In Rapid Detection Techniques For Pesticide Residue: A Review, Lingyuan Xu, A M Abd El-Aty, Jong-Bang Eun, Jae-Han Shim, Jing Zhao, Xingmei Lei, Song Gao, Yongxin She, Fen Jin, Jing Wang, Maojun Jin, Bruce D Hammock Oct 2022

Recent Advances In Rapid Detection Techniques For Pesticide Residue: A Review, Lingyuan Xu, A M Abd El-Aty, Jong-Bang Eun, Jae-Han Shim, Jing Zhao, Xingmei Lei, Song Gao, Yongxin She, Fen Jin, Jing Wang, Maojun Jin, Bruce D Hammock

Faculty, Staff and Student Publications

As an important chemical pollutant affecting the safety of agricultural products, the on-site and efficient detection of pesticide residues has become a global trend and hotspot in research. These methodologies were developed for simplicity, high sensitivity, and multiresidue detection. This review introduces the currently available technologies based on electrochemistry, optical analysis, biotechnology, and some innovative and novel technologies for the rapid detection of pesticide residues, focusing on the characteristics, research status, and application of the most innovative and novel technologies in the past 10 years, and analyzes challenges and future development prospects. The current review could be a good reference …


Hdac6 Inhibition Reverses Cisplatin-Induced Mechanical Hypersensitivity Via Tonic Delta Opioid Receptor Signaling, Jixiang Zhang, Jazzmine M Junigan, Ronnie Trinh, Annemieke Kavelaars, Cobi J Heijnen, Peter M Grace Oct 2022

Hdac6 Inhibition Reverses Cisplatin-Induced Mechanical Hypersensitivity Via Tonic Delta Opioid Receptor Signaling, Jixiang Zhang, Jazzmine M Junigan, Ronnie Trinh, Annemieke Kavelaars, Cobi J Heijnen, Peter M Grace

Faculty, Staff and Student Publications

Peripheral neuropathic pain induced by the chemotherapeutic cisplatin can persist for months to years after treatment. Histone deacetylase 6 (HDAC6) inhibitors have therapeutic potential for cisplatin-induced neuropathic pain since they persistently reverse mechanical hypersensitivity and spontaneous pain in rodent models. Here, we investigated the mechanisms underlying reversal of mechanical hypersensitivity in male and female mice by a 2 week treatment with an HDAC6 inhibitor, administered 3 d after the last dose of cisplatin. Mechanical hypersensitivity in animals of both sexes treated with the HDAC6 inhibitor was temporarily reinstated by a single injection of the neutral opioid receptor antagonist 6β-naltrexol or …


Anterior Connectivity Critical For Recovery Of Connected Speech After Stroke, Junhua Ding, Tatiana T Schnur Oct 2022

Anterior Connectivity Critical For Recovery Of Connected Speech After Stroke, Junhua Ding, Tatiana T Schnur

Faculty, Staff and Student Publications

Connected speech recovers to different degrees across people after left hemisphere stroke, but white matter predictors of differential recovery from the acute stage of stroke are unknown. We assessed changes in lexical-syntactic aspects of connected speech in a longitudinal analysis of 40 individuals (18 females) from the acute stage of left hemisphere stroke (within an average of 4 days post-stroke) to subacute (within 2 months) and chronic stages (early: 6 months, late: 1 year) while measuring the extent of acute lesions on white matter tracts to identify tracts predictive of recovery. We found that acute damage to the frontal aslant …


Mapping The Universe Of Eph Receptor And Ephrin Ligand Transcripts In Epithelial And Fiber Cells Of The Eye Lens, Michael P Vu, Catherine Cheng Oct 2022

Mapping The Universe Of Eph Receptor And Ephrin Ligand Transcripts In Epithelial And Fiber Cells Of The Eye Lens, Michael P Vu, Catherine Cheng

Faculty, Staff and Student Publications

The eye lens is a transparent, ellipsoid organ in the anterior chamber of the eye that is required for fine focusing of light onto the retina to transmit a clear image. Cataracts, defined as any opacity in the lens, remains the leading cause of blindness in the world. Recent studies in humans and mice indicate that Eph-ephrin bidirectional signaling is important for maintaining lens transparency. Specifically, mutations and polymorphisms in the EphA2 receptor and the ephrin-A5 ligand have been linked to congenital and age-related cataracts. It is unclear what other variants of Ephs and ephrins are expressed in the lens …


Estimating The Optimal Linear Combination Of Predictors Using Spherically Constrained Optimization, Priyam Das, Debsurya De, Raju Maiti, Mona Kamal, Katherine A Hutcheson, Clifton D Fuller, Bibhas Chakraborty, Christine B Peterson Oct 2022

Estimating The Optimal Linear Combination Of Predictors Using Spherically Constrained Optimization, Priyam Das, Debsurya De, Raju Maiti, Mona Kamal, Katherine A Hutcheson, Clifton D Fuller, Bibhas Chakraborty, Christine B Peterson

Faculty, Staff and Student Publications

Background: In the context of a binary classification problem, the optimal linear combination of continuous predictors can be estimated by maximizing the area under the receiver operating characteristic curve. For ordinal responses, the optimal predictor combination can similarly be obtained by maximization of the hypervolume under the manifold (HUM). Since the empirical HUM is discontinuous, non-differentiable, and possibly multi-modal, solving this maximization problem requires a global optimization technique. Estimation of the optimal coefficient vector using existing global optimization techniques is computationally expensive, becoming prohibitive as the number of predictors and the number of outcome categories increases.

Results: We propose an …


Therapeutic Efficacy Of The Humanized Jaa-F11 Anti-Thomsen-Friedenreich Antibody Constructs H2al2a And H3l3 In Human Breast And Lung Cancer Xenograft Models, Diala Ghazal, Fatma Zalzala, John C Fisk, Swetha Tati, Loukia G Karacosta, Susan Morey, James R Olson, Sally Quataert, Grace K Dy, Kate Rittenhouse-Olson Oct 2022

Therapeutic Efficacy Of The Humanized Jaa-F11 Anti-Thomsen-Friedenreich Antibody Constructs H2al2a And H3l3 In Human Breast And Lung Cancer Xenograft Models, Diala Ghazal, Fatma Zalzala, John C Fisk, Swetha Tati, Loukia G Karacosta, Susan Morey, James R Olson, Sally Quataert, Grace K Dy, Kate Rittenhouse-Olson

Faculty, Staff and Student Publications

The Thomsen-Friedenreich antigen (TF-Ag-α) is found on ~85% of human carcinomas but is cryptic on normal tissue. The humanized highly specific hJAA-F11-H2aL2a and -H3L3 antibodies target TF-Ag-α without binding to TF-Ag-beta (found on surface glycolipids of some normal cells). The relative affinity of H3L3 is 17 times that of H2aL2a, which would seem to favor superior efficacy, however, increased affinity can result in less tumor penetration. To assess the potential therapeutic efficacy of these antibodies, four human cancer- mouse xenograft models were treated with H2aL2a and H3L3. The tumor xenograft models used were human non-small cell lung cancer, H520, and …


Daphnia As A Sentinel Species For Environmental Health Protection: A Perspective On Biomonitoring And Bioremediation Of Chemical Pollution, Muhammad Abdullahi, Xiaojing Li, Mohamed Abou-Elwafa Abdallah, William Stubbings, Norman Yan, Marianne Barnard, Liang-Hong Guo, John K Colbourne, Luisa Orsini Oct 2022

Daphnia As A Sentinel Species For Environmental Health Protection: A Perspective On Biomonitoring And Bioremediation Of Chemical Pollution, Muhammad Abdullahi, Xiaojing Li, Mohamed Abou-Elwafa Abdallah, William Stubbings, Norman Yan, Marianne Barnard, Liang-Hong Guo, John K Colbourne, Luisa Orsini

Faculty, Staff and Student Publications

Despite available technology and the knowledge that chemical pollution damages human and ecosystem health, chemical pollution remains rampant, ineffectively monitored, rarely prevented, and only occasionally mitigated. We present a framework that helps address current major challenges in the monitoring and assessment of chemical pollution by broadening the use of the sentinel species Daphnia as a diagnostic agent of water pollution. And where prevention has failed, we propose the application of Daphnia as a bioremediation agent to help reduce hazards from chemical mixtures in the environment. By applying “omics” technologies to Daphnia exposed to real-world ambient chemical mixtures, we show improvements …


Association Of Mrna Vaccination With Clinical And Virologic Features Of Covid-19 Among Us Essential And Frontline Workers, The Heroes-Recover Network, Mark G Thompson, Sarang K Yoon, Allison L Naleway, Jennifer Meece, Thomas P Fabrizio, Alberto J Caban-Martinez, Jefferey L Burgess, Manjusha Gaglani, Lauren E W Olsho, Allen Bateman, Jessica Lundgren, Lauren Grant, Andrew L Phillips, Holly C Groom, Elisha Stefanski, Natasha Schaefer Solle, Katherine Ellingson, Karen Lutrick, Kayan Dunnigan, Meredith G Wesley, Kyley Guenther, Angela Hunt, Josephine Mak, Kurt T Hegmann, Jennifer L Kuntz, Adam Bissonnette, James Hollister, Spencer Rose, Tyler C Morrill, Karley Respet, Ashley L Fowlkes, Matthew S Thiese, Patrick Rivers, Meghan K Herring, Marilyn J Odean, Young M Yoo, Matthew Brunner, Edward J Bedrick, Deanna E Fleary, John T Jones, Jenna Praggastis, James Romine, Monica Dickerson, Sana M Khan, Julie Mayo Lamberte, Shawn Beitel, Richard J Webby, Harmony L Tyner Oct 2022

Association Of Mrna Vaccination With Clinical And Virologic Features Of Covid-19 Among Us Essential And Frontline Workers, The Heroes-Recover Network, Mark G Thompson, Sarang K Yoon, Allison L Naleway, Jennifer Meece, Thomas P Fabrizio, Alberto J Caban-Martinez, Jefferey L Burgess, Manjusha Gaglani, Lauren E W Olsho, Allen Bateman, Jessica Lundgren, Lauren Grant, Andrew L Phillips, Holly C Groom, Elisha Stefanski, Natasha Schaefer Solle, Katherine Ellingson, Karen Lutrick, Kayan Dunnigan, Meredith G Wesley, Kyley Guenther, Angela Hunt, Josephine Mak, Kurt T Hegmann, Jennifer L Kuntz, Adam Bissonnette, James Hollister, Spencer Rose, Tyler C Morrill, Karley Respet, Ashley L Fowlkes, Matthew S Thiese, Patrick Rivers, Meghan K Herring, Marilyn J Odean, Young M Yoo, Matthew Brunner, Edward J Bedrick, Deanna E Fleary, John T Jones, Jenna Praggastis, James Romine, Monica Dickerson, Sana M Khan, Julie Mayo Lamberte, Shawn Beitel, Richard J Webby, Harmony L Tyner

Faculty, Staff and Student Publications

IMPORTANCE: Data on the epidemiology of mild to moderately severe COVID-19 are needed to inform public health guidance.

OBJECTIVE: To evaluate associations between 2 or 3 doses of mRNA COVID-19 vaccine and attenuation of symptoms and viral RNA load across SARS-CoV-2 viral lineages.

DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of essential and frontline workers in Arizona, Florida, Minnesota, Oregon, Texas, and Utah with COVID-19 infection confirmed by reverse transcriptase-polymerase chain reaction testing and lineage classified by whole genome sequencing of specimens self-collected weekly and at COVID-19 illness symptom onset. This analysis was conducted among 1199 participants with SARS-CoV-2 …


Hospital Change To Mixed Lipid Emulsion From Soybean Oil-Based Lipid Emulsion For Parenteral Nutrition In Hospitalized And Critically Ill Adults Improves Outcomes: A Pre–Post-Comparative Study, Krista L Haines, Tetsu Ohnuma, Charles Trujillo, Obanor Osamudiamen, Vijay Krishnamoorthy, Karthik Raghunathan, Paul E Wischmeyer Oct 2022

Hospital Change To Mixed Lipid Emulsion From Soybean Oil-Based Lipid Emulsion For Parenteral Nutrition In Hospitalized And Critically Ill Adults Improves Outcomes: A Pre–Post-Comparative Study, Krista L Haines, Tetsu Ohnuma, Charles Trujillo, Obanor Osamudiamen, Vijay Krishnamoorthy, Karthik Raghunathan, Paul E Wischmeyer

Faculty, Staff and Student Publications

INTRODUCTION: Early data suggest use of a mixed lipid emulsion (LE) with a soybean oil reduction strategy in parenteral nutrition (PN) may improve clinical outcomes. Duke University Hospital made a full switch to a Soybean oil/MCT/Olive/Fish Oil lipid (4-OLE) from pure soybean oil-based LE (Intralipid, Baxter Inc) in May 2017. Since 4-OLE has limited evidence related to its effects on clinical outcome parameters in US hospitals, evidence for clinical benefits of switching to 4-OLE is needed. Therefore, we examined the clinical utility of a hospital-wide switch to 4-OLE and its effect on patient outcomes.

METHODS: We conducted a single-center retrospective …


The Mechanisms Of Action Of Tumor Treating Fields, Justin C Moser, Ellaine Salvador, Karina Deniz, Kenneth Swanson, Jack Tuszynski, Kristen W Carlson, Narasimha Kumar Karanam, Chirag B Patel, Michael Story, Emil Lou, Carsten Hagemann Oct 2022

The Mechanisms Of Action Of Tumor Treating Fields, Justin C Moser, Ellaine Salvador, Karina Deniz, Kenneth Swanson, Jack Tuszynski, Kristen W Carlson, Narasimha Kumar Karanam, Chirag B Patel, Michael Story, Emil Lou, Carsten Hagemann

Faculty, Staff and Student Publications

Tumor treating fields (TTFields), a new modality of cancer treatment, are electric fields transmitted transdermally to tumors. The FDA has approved TTFields for the treatment of glioblastoma multiforme and mesothelioma, and they are currently under study in many other cancer types. While antimitotic effects were the first recognized biological anticancer activity of TTFields, data have shown that tumor treating fields achieve their anticancer effects through multiple mechanisms of action. TTFields therefore have the ability to be useful for many cancer types in combination with many different treatment modalities. Here, we review the current understanding of TTFields and their mechanisms of …


Serological Evidence Of Severe Fever With Thrombocytopenia Syndrome Virus And Igm Positivity Were Identified In Healthy Residents In Vietnam, Xuan Chuong Tran, Sung Hye Kim, Jeong-Eun Lee, So-Hee Kim, Su Yeon Kang, Nguyen D Binh, Pham V Duc, Phan T K Phuong, Nguyen T P Thao, Wonwoo Lee, Joon-Yong Bae, Man-Seong Park, Misun Kim, Jeong Rae Yoo, Sang Taek Heo, Kyeong Ho An, Jung Mogg Kim, Nam-Hyuk Cho, Sun-Ho Kee, Keun Hwa Lee Oct 2022

Serological Evidence Of Severe Fever With Thrombocytopenia Syndrome Virus And Igm Positivity Were Identified In Healthy Residents In Vietnam, Xuan Chuong Tran, Sung Hye Kim, Jeong-Eun Lee, So-Hee Kim, Su Yeon Kang, Nguyen D Binh, Pham V Duc, Phan T K Phuong, Nguyen T P Thao, Wonwoo Lee, Joon-Yong Bae, Man-Seong Park, Misun Kim, Jeong Rae Yoo, Sang Taek Heo, Kyeong Ho An, Jung Mogg Kim, Nam-Hyuk Cho, Sun-Ho Kee, Keun Hwa Lee

Faculty, Staff and Student Publications

Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne viral disease, is prevalent in East Asia and has also been reported in Southeast Asia since 2019. SFTS patients in Vietnam were first reported in 2019. However, the seroprevalence of severe fever with thrombocytopenia syndrome virus (SFTSV) in Vietnam has not been reported. To investigate the seroprevalence of SFTSV in Vietnam, we collected serum samples from 714 healthy residents in Thua Thien Hue and Quang Nam Province, Vietnam, and the seroprevalence of SFTSV was assessed using immunofluorescence antibody assay (IFA), Enzyme-Linked Immunosorbent Assays (ELISAs) and the 50% focus reduction neutralization test …


Tumor Microenvironment: Barrier Or Opportunity Towards Effective Cancer Therapy, Aadhya Tiwari, Rakesh Trivedi, Shiaw-Yih Lin Oct 2022

Tumor Microenvironment: Barrier Or Opportunity Towards Effective Cancer Therapy, Aadhya Tiwari, Rakesh Trivedi, Shiaw-Yih Lin

Faculty, Staff and Student Publications

Tumor microenvironment (TME) is a specialized ecosystem of host components, designed by tumor cells for successful development and metastasis of tumor. With the advent of 3D culture and advanced bioinformatic methodologies, it is now possible to study TME's individual components and their interplay at higher resolution. Deeper understanding of the immune cell's diversity, stromal constituents, repertoire profiling, neoantigen prediction of TMEs has provided the opportunity to explore the spatial and temporal regulation of immune therapeutic interventions. The variation of TME composition among patients plays an important role in determining responders and non-responders towards cancer immunotherapy. Therefore, there could be a …


Central Nervous System (Cns) Inflammatory Demyelinating Diseases (Idds) Associated With Covid-19: A Case Series And Review, Parissa Feizi, Kanika Sharma, Shreya R Pasham, Lalit Nirwan, Joe Joseph, Shruti Jaiswal, Shitiz Sriwastava Oct 2022

Central Nervous System (Cns) Inflammatory Demyelinating Diseases (Idds) Associated With Covid-19: A Case Series And Review, Parissa Feizi, Kanika Sharma, Shreya R Pasham, Lalit Nirwan, Joe Joseph, Shruti Jaiswal, Shitiz Sriwastava

Faculty, Staff and Student Publications

BACKGROUND: Over the past two years, SARS-CoV-2 has frequently been documented with various post and para-infectious complications, including cerebrovascular, neuromuscular, and some demyelinating conditions such as acute disseminated encephalomyelitis (ADEM). We report two rare neurological manifestations post-COVID-19 infection; multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Further, we reviewed other CNS inflammatory demyelinating diseases (IDDs) associated with SARS-CoV-2, including optic neuritis (ON) and neuromyelitis optica spectrum disorders (NMOSD).

METHODS: A descriptive analysis and literature search of Google Scholar and PubMed was conducted by two independent reviewers from December 1st, 2019, to March 30th, 2022, and included all the …


Machine Learning On Syngeneic Mouse Tumor Profiles To Model Clinical Immunotherapy Response, Zexian Zeng, Shengqing Stan Gu, Cheryl J Wong, Lin Yang, Nofal Ouardaoui, Dian Li, Wubing Zhang, Myles Brown, X Shirley Liu Oct 2022

Machine Learning On Syngeneic Mouse Tumor Profiles To Model Clinical Immunotherapy Response, Zexian Zeng, Shengqing Stan Gu, Cheryl J Wong, Lin Yang, Nofal Ouardaoui, Dian Li, Wubing Zhang, Myles Brown, X Shirley Liu

Faculty, Staff and Student Publications

Most patients with cancer are refractory to immune checkpoint blockade (ICB) therapy, and proper patient stratification remains an open question. Primary patient data suffer from high heterogeneity, low accessibility, and lack of proper controls. In contrast, syngeneic mouse tumor models enable controlled experiments with ICB treatments. Using transcriptomic and experimental variables from >700 ICB-treated/control syngeneic mouse tumors, we developed a machine learning framework to model tumor immunity and identify factors influencing ICB response. Projected on human immunotherapy trial data, we found that the model can predict clinical ICB response. We further applied the model to predicting ICB-responsive/resistant cancer types in …


Combined Trip13 And Aurora Kinase Inhibition Induces Apoptosis In Human Papillomavirus-Driven Cancers, Soma Ghosh, Tuhina Mazumdar, Wei Xu, Reid T Powell, Clifford Stephan, Li Shen, Pooja A Shah, Curtis R Pickering, Jeffery N Myers, Jing Wang, Mitchell J Frederick, Faye M Johnson Oct 2022

Combined Trip13 And Aurora Kinase Inhibition Induces Apoptosis In Human Papillomavirus-Driven Cancers, Soma Ghosh, Tuhina Mazumdar, Wei Xu, Reid T Powell, Clifford Stephan, Li Shen, Pooja A Shah, Curtis R Pickering, Jeffery N Myers, Jing Wang, Mitchell J Frederick, Faye M Johnson

Faculty, Staff and Student Publications

PURPOSE: Human papillomavirus (HPV) causes >5% of cancers, but no therapies uniquely target HPV-driven cancers.

EXPERIMENTAL DESIGN: We tested the cytotoxic effect of 864 drugs in 16 HPV-positive and 17 HPV-negative human squamous cancer cell lines. We confirmed apoptosis in vitro and in vivo using patient-derived xenografts. Mitotic pathway components were manipulated with drugs, knockdown, and overexpression.

RESULTS: Aurora kinase inhibitors were more effective in vitro and in vivo in HPV-positive than in HPV-negative models. We hypothesized that the mechanism of sensitivity involves retinoblastoma (Rb) expression because the viral oncoprotein E7 leads to Rb protein degradation, and basal Rb protein …


Human Nop2/Nsun1 Regulates Ribosome Biogenesis Through Non-Catalytic Complex Formation With Box C/D Snornps, Han Liao, Anushri Gaur, Hunter Mcconie, Amirtha Shekar, Karen Wang, Jeffrey T Chang, Ghislain Breton, Catherine Denicourt Oct 2022

Human Nop2/Nsun1 Regulates Ribosome Biogenesis Through Non-Catalytic Complex Formation With Box C/D Snornps, Han Liao, Anushri Gaur, Hunter Mcconie, Amirtha Shekar, Karen Wang, Jeffrey T Chang, Ghislain Breton, Catherine Denicourt

Faculty, Staff and Student Publications

5-Methylcytosine (m5C) is a base modification broadly found on various RNAs in the human transcriptome. In eukaryotes, m5C is catalyzed by enzymes of the NSUN family composed of seven human members (NSUN1-7). NOP2/NSUN1 has been primarily characterized in budding yeast as an essential ribosome biogenesis factor required for the deposition of m5C on the 25S ribosomal RNA (rRNA). Although human NOP2/NSUN1 has been known to be an oncogene overexpressed in several types of cancer, its functions and substrates remain poorly characterized. Here, we used a miCLIP-seq approach to identify human NOP2/NSUN1 RNA substrates. Our analysis revealed that NOP2/NSUN1 catalyzes the …


Columnar Metaplasia Of The Esophagus Presenting As Iron Deficiency Anemia In Children With Neurologic Impairment Or Congenital Esophageal Atresia, Melissa R Van Arsdall, Supriya Nair, Lindsay M Moye, Trinh T Nguyen, Zeina M Saleh, J Marc Rhoads Oct 2022

Columnar Metaplasia Of The Esophagus Presenting As Iron Deficiency Anemia In Children With Neurologic Impairment Or Congenital Esophageal Atresia, Melissa R Van Arsdall, Supriya Nair, Lindsay M Moye, Trinh T Nguyen, Zeina M Saleh, J Marc Rhoads

Faculty, Staff and Student Publications

BACKGROUND Columnar metaplasia of the lower esophagus includes both gastric and intestinal metaplasia. Children with severe neurologic impairment and congenital esophageal atresia often have gastroesophageal reflux disease, which can lead to Barrett's esophagus, a form of lower esophageal columnar metaplasia and precursor to esophageal adenocarcinoma, with some, but not all, guidelines specifically requiring the presence of intestinal metaplasia for diagnosis. This case series illustrates how iron deficiency anemia may be the primary symptom of esophageal columnar metaplasia in such children and how upper endoscopy is essential in their initial and ongoing evaluation. CASE REPORT We review 5 cases of columnar …


Columnar Metaplasia Of The Esophagus Presenting As Iron Deficiency Anemia In Children With Neurologic Impairment Or Congenital Esophageal Atresia, Melissa R Van Arsdall, Supriya Nair, Lindsay M Moye, Trinh T Nguyen, Zeina M Saleh, J Marc Rhoads Oct 2022

Columnar Metaplasia Of The Esophagus Presenting As Iron Deficiency Anemia In Children With Neurologic Impairment Or Congenital Esophageal Atresia, Melissa R Van Arsdall, Supriya Nair, Lindsay M Moye, Trinh T Nguyen, Zeina M Saleh, J Marc Rhoads

Faculty, Staff and Student Publications

BACKGROUND Columnar metaplasia of the lower esophagus includes both gastric and intestinal metaplasia. Children with severe neurologic impairment and congenital esophageal atresia often have gastroesophageal reflux disease, which can lead to Barrett's esophagus, a form of lower esophageal columnar metaplasia and precursor to esophageal adenocarcinoma, with some, but not all, guidelines specifically requiring the presence of intestinal metaplasia for diagnosis. This case series illustrates how iron deficiency anemia may be the primary symptom of esophageal columnar metaplasia in such children and how upper endoscopy is essential in their initial and ongoing evaluation. CASE REPORT We review 5 cases of columnar …


2022 Practice Recommendation Updates From The World Consensus Conference On Bia-Alcl, Fabio Santanelli Di Pompeo, Mark W Clemens, Michael Atlan, Giovanni Botti, Peter G Cordeiro, Daphne De Jong, Arianna Di Napoli, Dennis Hammond, Cara L Haymaker, Steven M Horwitz, Kelly Hunt, Peter Lennox, Patrick Mallucci, Roberto N Miranda, Alexandre M Munhoz, Eric Swanson, Suzanne D Turner, Guido Firmani, Michail Sorotos Oct 2022

2022 Practice Recommendation Updates From The World Consensus Conference On Bia-Alcl, Fabio Santanelli Di Pompeo, Mark W Clemens, Michael Atlan, Giovanni Botti, Peter G Cordeiro, Daphne De Jong, Arianna Di Napoli, Dennis Hammond, Cara L Haymaker, Steven M Horwitz, Kelly Hunt, Peter Lennox, Patrick Mallucci, Roberto N Miranda, Alexandre M Munhoz, Eric Swanson, Suzanne D Turner, Guido Firmani, Michail Sorotos

Faculty, Staff and Student Publications

BACKGROUND: Laboratory and clinical research on breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is rapidly evolving. Changes in standard of care and insights into best practice were recently presented at the 3rd World Consensus Conference on BIA-ALCL.

OBJECTIVES: The authors sought to provide practice recommendations from a consensus of experts, supplemented with a literature review regarding epidemiology, etiology, pathogenesis, diagnosis, treatment, socio-psychological aspects, and international authority guidance.

METHODS: A literature search of all manuscripts between 1997 and August 2021 for the above areas of BIA-ALCL was conducted with the PubMed database. Manuscripts in different languages, on non-human subjects, and/or discussing …


Immunotherapeutic Approaches For Treating Hepatocellular Carcinoma, Wanying Shen, Yujie Chen, Pan Lei, Marisela Sheldon, Yutong Sun, Fan Yao, Li Ma Oct 2022

Immunotherapeutic Approaches For Treating Hepatocellular Carcinoma, Wanying Shen, Yujie Chen, Pan Lei, Marisela Sheldon, Yutong Sun, Fan Yao, Li Ma

Faculty, Staff and Student Publications

Liver cancer is a life-threatening disease, and its incidence is increasing globally. The most common form of liver cancer is hepatocellular carcinoma (HCC). Approximately half of patients with HCC, especially those at advanced disease stages, receive systemic therapies, including the tyrosine kinase inhibitors sorafenib and lenvatinib. Over the past few years, immune checkpoint inhibitors (ICIs) have changed the landscape of HCC treatment. In particular, the combination therapy with atezolizumab (an anti-PD-L1 antibody) and bevacizumab (an anti-VEGF antibody) significantly improved survival benefits compared with sorafenib as a single agent, a finding that has stimulated further preclinical and clinical development of immunotherapeutic …


Public Health Burden Of Secondhand Smoking: Case Reports Of Lung Cancer And A Literature Review, Ladislav Štěpánek, Jarmila Ševčíková, Dagmar Horáková, Mihir Sanjay Patel, Radka Durďáková Oct 2022

Public Health Burden Of Secondhand Smoking: Case Reports Of Lung Cancer And A Literature Review, Ladislav Štěpánek, Jarmila Ševčíková, Dagmar Horáková, Mihir Sanjay Patel, Radka Durďáková

Faculty, Staff and Student Publications

Secondhand smoke (SHS), composed of mainstream and sidestream smoke, is a known human carcinogen. It contains a variety of harmful substances at even higher concentrations than mainstream smoke itself, which is inhaled during firsthand smoking. Exposure to SHS, affecting more than a third of the worldwide population, increases the likelihood of lung cancer by roughly 30%, with specific contributions depending on the histological type of cancer. This study aimed to present the harmful potential of SHS through case reports and describe the burden of SHS via a literature review. From a collection of lung cancer case reports occurring in never …


Deep Learning Models For Automated Assessment Of Breast Density Using Multiple Mammographic Image Types, Bastien Rigaud, Olena O Weaver, Jennifer B Dennison, Muhammad Awais, Brian M Anderson, Ting-Yu D Chiang, Wei T Yang, Jessica W T Leung, Samir M Hanash, Kristy K Brock Oct 2022

Deep Learning Models For Automated Assessment Of Breast Density Using Multiple Mammographic Image Types, Bastien Rigaud, Olena O Weaver, Jennifer B Dennison, Muhammad Awais, Brian M Anderson, Ting-Yu D Chiang, Wei T Yang, Jessica W T Leung, Samir M Hanash, Kristy K Brock

Faculty, Staff and Student Publications

Recently, convolutional neural network (CNN) models have been proposed to automate the assessment of breast density, breast cancer detection or risk stratification using single image modality. However, analysis of breast density using multiple mammographic types using clinical data has not been reported in the literature. In this study, we investigate pre-trained EfficientNetB0 deep learning (DL) models for automated assessment of breast density using multiple mammographic types with and without clinical information to improve reliability and versatility of reporting. 120,000 for-processing and for-presentation full-field digital mammograms (FFDM), digital breast tomosynthesis (DBT), and synthesized 2D images from 5032 women were retrospectively analyzed. …