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Articles 24901 - 24930 of 31465
Full-Text Articles in Entire DC Network
Quality Risk Management: A Role-Based Competency Model For The Biopharmaceutical Sector, Ghada Haddad
Quality Risk Management: A Role-Based Competency Model For The Biopharmaceutical Sector, Ghada Haddad
Journal of Applied Pharmaceutical Regulatory Science
In 2005, the International Conference on Harmonisation’s (ICH’s) ‘’Q9’’, aimed at providing the biopharmaceutical sector with guidance towards a science and risk-based approach to quality management was published. The concepts outlined in ICH Q9 focused on the fact that evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient.
The purpose of ICH Q9 is to offer a systematic approach to quality risk management (QRM). It serves as a foundation or resource document that is independent of yet supports other ICH Quality documents and complements existing quality practices, requirements, …
Taking A Stand For Quality: Demonstrating Pqs Effectiveness By Operationalizing Qrm And Km, Kevin O'Donnell, Martin J. Lipa, Anne Greene (Editor)
Taking A Stand For Quality: Demonstrating Pqs Effectiveness By Operationalizing Qrm And Km, Kevin O'Donnell, Martin J. Lipa, Anne Greene (Editor)
Journal of Applied Pharmaceutical Regulatory Science
While the authors have published widely on the need to unite the twin enablers of ICH Q10 [1], quality risk management (QRM) and knowledge management (KM), how to integrate QRM and KM in practice has proven to be quite challenging. QRM and KM are wide-ranging activities that impact many elements of pharmaceutical manufacturing and regulation. Pharmaceutical manufacturers and their regulators work to apply risk-based approaches to their work and strive to use knowledge in a smart and efficient way, but so far, in the experience of the authors, it has proven difficult to get these things right.
One way to …
Towards A New Era Of Surgery Using Intelligent Robot, Ahmed Mahfouz, Hassan A. El Gamal, T. Awad, M.B. Badawi
Towards A New Era Of Surgery Using Intelligent Robot, Ahmed Mahfouz, Hassan A. El Gamal, T. Awad, M.B. Badawi
Journal of Engineering Research
This research aims to overcome the difficulties of surgical tumor removal, especially in brain tumors that needs precision and time saving of the operations. The traditional surgical approach often is slow and targeting accurate manual cutting of the tumor, which is time-consuming and increase the risk to the patient. The error in cutting the deep layers of the tumor can occur, which increase the cost and dangerous for the patient.
To overcome these challenges, a proposed solution involves designing a robot that can quickly and accurately remove tumors by following their contours as it comes from the medical imaging data, …
A Non-Standard Finite Difference Approach For Optimizing The Thermal Behaviour Of Photovoltaic Panel With Hybrid Cooling Techniques, E.F. El-Gazar, A.A Hawwash, Hamdy Hassan, Shinsuke Mori, Ayman Refat Abd Elbar
A Non-Standard Finite Difference Approach For Optimizing The Thermal Behaviour Of Photovoltaic Panel With Hybrid Cooling Techniques, E.F. El-Gazar, A.A Hawwash, Hamdy Hassan, Shinsuke Mori, Ayman Refat Abd Elbar
Journal of Engineering Research
A finite difference model is developed to simulate the thermal behaviour of the PV system with an innovative cooling system. The proposed cooling system combines an aluminium heat spreader (AHS) with phase change material (PCM) placed at the backside of the solar panel. The new non-standard model is solved using MATLAB software and is validated with real experimental data collected under hot climate conditions. The new nonlocal model is found to be more effective in analyzing heat transfer processes throughout the entirety of the PV system compared to conventional PV models. Additionally, the new cooling PV system has been compared …
Assessment Of Physical And Ergonomic Hazards And Their Compliance With National Standards. A Case Study, Amira Abdelraheem
Assessment Of Physical And Ergonomic Hazards And Their Compliance With National Standards. A Case Study, Amira Abdelraheem
Journal of Engineering Research
Occupational hazards are a significant concern in high-risk environments such as petroleum operating companies, where workers are exposed to various risks, including chemical, physical, mechanical, ergonomic, and psychosocial factors. Effective management of these hazards is essential to protect the health and safety of employees and maintain operational efficiency. This study aims to assess physical hazards including a-weighted equivalent noise levels, heat stress, Lightning and Ergonomics in a petroleum operating company in Egypt, and to check its conformity with national standards. Physical environment (Noise, heat stress and illumination) in different worksites were assessed using calibrated direct reading instruments to evaluate the …
Lessons Learned From The Covid-19 Pandemic Crisis Management In The Gaza Strip: A Qualitative Study., Belal Aljamal
Lessons Learned From The Covid-19 Pandemic Crisis Management In The Gaza Strip: A Qualitative Study., Belal Aljamal
Journal of the Arab American University مجلة الجامعة العربية الامريكية للبحوث
Aims of the study: The main aim of this study was to discover the lessons learned from the COVID-19 pandemic crisis management from health policymakers' perspective in the Gaza Strip. Methods: The researcher used a qualitative design, targeting 25health policymakers using a purposeful sampling technique and face-to-face semi-structured interviews to collect data. To analyze the interview data, the directed qualitative content analysis approach was used.
Results: All interviewees agreed that the Palestinian Ministry of Health (MoH) managed the COVID-19pandemic well despite the insufficient resources and lack of experience. More specifically, the average of most participants’ assessments of Palestinian MoH “Preparedness” …
The Impact Of Adopting Unicef Growth And Development Modules In Enhancing Nursing Students' Knowledge: A Qualitative Study, Yousef Eljeesh, Mahmoud Ayash
The Impact Of Adopting Unicef Growth And Development Modules In Enhancing Nursing Students' Knowledge: A Qualitative Study, Yousef Eljeesh, Mahmoud Ayash
Journal of the Arab American University مجلة الجامعة العربية الامريكية للبحوث
Background: The growth and development phase are an essential and critical period of human life, especially in the early stages. It was defined by most professionals as the interval from conception to eight years of age. This interval is vital for brain growth. In addition, these developmental years have a significant and lifelong impact on children. Thus, almost all children in these years need to be well cared. Aim: The study aimed to assess the impact of adopting UNICEF modules on nursing students' knowledge about growth and development concepts. Design: A qualitative study design was used to conduct the study. …
Unlocking Nature’S Ice-Binders, Nicholas Gosling
Unlocking Nature’S Ice-Binders, Nicholas Gosling
UNH Today Archive
No abstract provided.
Species Differences In The Biotransformation Of Aflatoxin B1: Primary Determinants Of Relative Carcinogenic Potency In Different Animal Species, David L. Eaton, David E. Williams, Roger A. Coulombe
Species Differences In The Biotransformation Of Aflatoxin B1: Primary Determinants Of Relative Carcinogenic Potency In Different Animal Species, David L. Eaton, David E. Williams, Roger A. Coulombe
Animal, Dairy, and Veterinary Science Faculty Publications
It has been known since the early days of the discovery of aflatoxin B1 (AFB1) that there were large species differences in susceptibility to AFB1. It was also evident early on that AFB1 itself was not toxic but required bioactivation to a reactive form. Over the past 60 years there have been thousands of studies to delineate the role of ~10 specific biotransformation pathways of AFB1, both phase I (oxidation, reduction) and phase II (hydrolysis, conjugation, secondary oxidations, and reductions of phase I metabolites). This review provides a historical context and substantive analysis of each of these pathways as contributors …
Elementary Teachers’ Experiences Supporting The Academic Growth And Development Of Students On The Autism Spectrum In Inclusion Classrooms, Erica Williams Harryman
Elementary Teachers’ Experiences Supporting The Academic Growth And Development Of Students On The Autism Spectrum In Inclusion Classrooms, Erica Williams Harryman
Walden Dissertations and Doctoral Studies
The problem addressed in this study is that elementary inclusion teachers in urban school districts in a northeastern state in the United States struggle to support the academic growth and development of their students with autism spectrum disorder (ASD). The purpose of this study was to explore the experiences of these teachers and identify the institutional conditions they perceive as necessary to foster positive academic outcomes for students with ASD, informing the study's two research questions. Framed by Bandura’s social cognitive theory, particularly its principle of triadic reciprocality, the study employed a basic qualitative design. Twelve elementary inclusion teachers participated …
Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada
Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a by-product of TDP43 autoregulation and cleared by nonsense-mediated RNA decay (NMD). sTDP43-encoding transcripts that escape NMD are rapidly degraded post-translationally via the proteasome …
Extensive Admixture Among Karst-Obligate Salamanders Reveals Evidence Of Recent Divergence And Gene Exchange Through Aquifers, Chris C. Nice, Katherine L. Bell, Zachariah Gompert, Lauren K. Lucas, James R. Ott, Ruben U. Tovar, Paul Crump, Peter H. Diaz
Extensive Admixture Among Karst-Obligate Salamanders Reveals Evidence Of Recent Divergence And Gene Exchange Through Aquifers, Chris C. Nice, Katherine L. Bell, Zachariah Gompert, Lauren K. Lucas, James R. Ott, Ruben U. Tovar, Paul Crump, Peter H. Diaz
Biology Faculty Publications
Karst ecosystems often contain extraordinary biodiversity, but the complex underground aquifers of karst regions present challenges for assessing and conserving stygobiont diversity and investigating their evolutionary history. We examined the karst-obligate salamanders of the Eurycea neotenes species complex in the Edwards Plateau region of central Texas using population genomics data to address questions about population connectivity and the potential for gene exchange within the underlying aquifer system. The E. neotenes species complex has historically been divided into three nominal species, but their status, and spatial extent of species ranges, have remained uncertain. We discovered evidence of extensive admixture among species …
Effects Of Pericarp Removal And Different Germination Conditions On Seed Germination And Saline-Alkali Tolerance Of Amorpha Fruticosa, Zhan-Wu Gao, Yong-Guang Mu, Feng Chen, Li-Jie He, Xin-Ning Li, Jia-Tong Li, Ke-Jia Ding, Yan-Hui Cu, Chun-Sheng Mu, Adnan Rasheed
Effects Of Pericarp Removal And Different Germination Conditions On Seed Germination And Saline-Alkali Tolerance Of Amorpha Fruticosa, Zhan-Wu Gao, Yong-Guang Mu, Feng Chen, Li-Jie He, Xin-Ning Li, Jia-Tong Li, Ke-Jia Ding, Yan-Hui Cu, Chun-Sheng Mu, Adnan Rasheed
Turkish Journal of Botany
In this paper, neutral salt NaCl and basic salt Na2CO3 were used to simulate salt stress and alkali stress respectively, and the effects of salt stress and alkali stress on seed germination and growth changes in natural saline-alkali soil were studied, in order to provide theoretical basis for making full use of plant resources and improving production efficiency. The fruit peel of Amorpha fruticosa contains a lot of lipids, which has a significant effect on seed germination. Under salt stress, removal of pericarp significantly increased germination rate, germination potential and germination index (P< 0.05), and significantly shortened germination time of seeds (p< 0.05), which accelerated the establishment of seedlings, reduced the stress time during germination, and advanced the transition from heterotrophic to autotrophic, accumulating more anions and organic solutes to adapt to salt stress. Therefore, when planting in neutral salt soil, it can be used to remove the peel for sowing to improve the planting effect. However, under alkali stress, the growth is inhibited by the absorption of a large amount of Na+ and high pH value, so it is not suitable for removing the peel for sowing. Different germination conditions had significant effects on seed germination. The length and biomass of radicle and germ in sand culture were significantly higher than those in paper culture (P< 0.05). Under the condition of sand culture, the concentration of the treatment solution can be well maintained, which is conducive to fixing the seedlings and reducing the interference of other mineral elements. Therefore, sand culture method is recommended for seed germination experiments under stress, especially for plants with developed roots.
Impact Of Anoxygenic Phototrophic Bacteria On The Growth Of Arabidopsis Thaliana Under Salt Stress, Behi̇ye Nur Aksoy, Hamza Ettadili, Caner Vural
Impact Of Anoxygenic Phototrophic Bacteria On The Growth Of Arabidopsis Thaliana Under Salt Stress, Behi̇ye Nur Aksoy, Hamza Ettadili, Caner Vural
Turkish Journal of Botany
The effect of a microbial mixture containing anoxygenic phototrophic bacteria (APB) on the growth of Arabidopsis thaliana ecotype Col-0 under salt stress was investigated. To induce salt stress, 150 mM NaCl was applied to A. thaliana. Four treatments were employed to assess the impact of APB: (1) control plants, (2) plants inoculated with a mixture of enriched photosynthetic bacteria, (3) plants inoculated with a mixture of enriched photosynthetic bacteria and irrigated with 150 mM NaCl solution, and (4) plants irrigated with 150 mM NaCl solution. The analysis demonstrated that the inoculated plants exhibited increased leaf formation and leafsize. Furthermore, an …
Microrna 133a Regulates Squalene Epoxidase Expression In Colorectal Cancer Cells To Control Cell Proliferation And Cholesterol Production, Ji Su Mo, Santosh Lamichhane, Grinsun Sharma, Soo Cheon Chae
Microrna 133a Regulates Squalene Epoxidase Expression In Colorectal Cancer Cells To Control Cell Proliferation And Cholesterol Production, Ji Su Mo, Santosh Lamichhane, Grinsun Sharma, Soo Cheon Chae
School of Medicine Faculty Publications
Background/Objectives: Colorectal cancer (CRC) is one of the most common cancers worldwide, with high incidence and mortality rates. MicroRNAs are endogenous and non-coding RNAs that play a pivotal role in the development and progression of various cancers by targeting specific genes. Previously, we identified MIR133A to be significantly decreased in human CRC tissues. This study aims to identify the relationship with SQLE, one of the candidate target genes of MIR133A, and study their interaction in CRC cells. Methods: Through the luciferase reporter assay, quantitative RT-PCR (qRT-PCR), and Western blot analysis. Results: We identified SQLE as a direct target gene of …
Molecular Identification And Functional Characterization Of A Stilbene Synthase Gene In Rheum Officinale, Gaoxin Hao, Mengmeng Liu, Qiao Du, Xia Zhao, Feng Yan, Xiaochen Hu, Jing Gao, Liang Peng, Yimin Li, Gang Zhang
Molecular Identification And Functional Characterization Of A Stilbene Synthase Gene In Rheum Officinale, Gaoxin Hao, Mengmeng Liu, Qiao Du, Xia Zhao, Feng Yan, Xiaochen Hu, Jing Gao, Liang Peng, Yimin Li, Gang Zhang
Turkish Journal of Botany
Stilbene synthase (STS), is a pivotal gene involved in the biosynthesis and regulation of stilbenes compounds, playing a crucial role in plant growth, development and stress adaptation. Meantime, stilbene compounds hold promising prospects of the wide-ranging clinical applications. Rheum officinale contains abundant stilbene compounds, yet the precise regulatory genes governing their biosynthesis remain elusive. In this study, the ORF of RoSTS gene was amplified, yielding a length of 1,140 bp and encoding a protein consisting of 379 amino acids with a relative molecular mass of 41 640.25 Da. The RoSTS protein contained the conserved residues (Cys 164, His 303, and …
Acetylcholine Treatments Enhance Growth, Photosynthesis Efficiency And Stress Resilience In Maize Seedlings Exposed To Arsenic, Büşra Arikan-Abdulveli
Acetylcholine Treatments Enhance Growth, Photosynthesis Efficiency And Stress Resilience In Maize Seedlings Exposed To Arsenic, Büşra Arikan-Abdulveli
Turkish Journal of Botany
Arsenic (As) is a widespread and highly toxic metalloid that adversely affects plant health, leading to reduced yields, impaired photosynthesis, and compromised root structures. Although acetylcholine (ACh), a neurotransmitter implicated in plant growth and stress responses, has shown potential in mitigating heavy metal stress, its effects on As stress in maize (Zea mays L.) remain largely unexplored. This study investigated the impact of ACh treatments on maize seedlings exposed to As stress (100 µM), focusing on physiological responses, growth rates, photosynthesis, and the antioxidant system. Our findings revealed that ACh treatments conferred differential protective effects against As stress. The lowest …
Ghost Fishing Due To Derelict Crab Traps In Louisiana’S Barataria Basin, Emma C. Villemarette
Ghost Fishing Due To Derelict Crab Traps In Louisiana’S Barataria Basin, Emma C. Villemarette
LSU Master's Theses
Ghost fishing, the unintentional entrapment of sea life by derelict fishing gear, is an ecologic and socioeconomic concern in Louisiana's crabbing industry (blue crab, Callinectes sapidus). These ghost fishing traps cause unknown and unaccounted for mortality in blue crab and bycatch species. I aimed to track changes to derelict crab trap catch and trap deterioration over seasons and between habitats. I set and monitored 33 simulated derelict crab traps over 367 soak days in three varying habitats along Barataria Bay, Louisiana. Traps were checked once every two weeks and an additional daily check for five days per season. Blue …
Novel Synthetic Circuits For Cellular Theranostic Applications, Leah Nicole Davis
Novel Synthetic Circuits For Cellular Theranostic Applications, Leah Nicole Davis
Theses and Dissertations
Cancer is a complex disease that leads to over 600,000 deaths in the United States each year. Immunoengineering, the process of harnessing a patient's immune system to treat disease, has proven to be a promising therapeutic approach for cancer. For example, the FDA has approved seven chimeric antigen receptor T-cell (CAR-T) therapies. However, these therapies address less than 11% of cancers diagnosed in the United States. In this work, we develop innovative tools to enhance immunoengineering and the efficacy of cell therapies like CAR-T. We introduce and validate synthetic phosphorylation networks with fluorescent and luminescent extension (SPN-FLUX), a synthetic receptor …
Global Estimates Of The Storage And Transit Time Of Water Through Vegetation, Andrew Felton, Joshua B. Fisher, Koen Hufkens, Adam J. Purdy, Seth A. Spawn-Lee, Lou F. Duloisy, Gregory R. Goldsmith
Global Estimates Of The Storage And Transit Time Of Water Through Vegetation, Andrew Felton, Joshua B. Fisher, Koen Hufkens, Adam J. Purdy, Seth A. Spawn-Lee, Lou F. Duloisy, Gregory R. Goldsmith
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
The time it takes for water to transit from the ground back to the atmosphere affects weather, climate, biogeochemistry and ecosystem function. The transit time of water through vegetation, defined as the age of water transpiring from vegetation since time of entry, is a particularly understudied aspect of the terrestrial hydrologic cycle. Here we use a synergy of satellite remote sensing measurements over a five-year period to estimate global aboveground vegetation water storage to be on average 484 km3, roughly half of which is stored in Earth’s water-limited savannah, grassland and shrubland ecosystems. We then combine these storage …
Elementary Teachers’ Experiences Supporting The Academic Growth And Development Of Students On The Autism Spectrum In Inclusion Classrooms, Erica Williams Harryman
Elementary Teachers’ Experiences Supporting The Academic Growth And Development Of Students On The Autism Spectrum In Inclusion Classrooms, Erica Williams Harryman
Walden Dissertations and Doctoral Studies
The problem addressed in this study is that elementary inclusion teachers in urban school districts in a northeastern state in the United States struggle to support the academic growth and development of their students with autism spectrum disorder (ASD). The purpose of this study was to explore the experiences of these teachers and identify the institutional conditions they perceive as necessary to foster positive academic outcomes for students with ASD, informing the study's two research questions. Framed by Bandura’s social cognitive theory, particularly its principle of triadic reciprocality, the study employed a basic qualitative design. Twelve elementary inclusion teachers participated …
On Translating Adelina Gurrea’S “La Doncella Que Vivió Tres Vidas”, Jonathan Chua, Ma. Luisa Young
On Translating Adelina Gurrea’S “La Doncella Que Vivió Tres Vidas”, Jonathan Chua, Ma. Luisa Young
Perspectives in the Arts and Humanities Asia
This is an account of the translation process that went into the English translation of the story “La doncella que vivió tres vidas” (1943) by Adelina Gurrea, a writer of Spanish and Filipino descent. Gurrea’s Cuentos de Juana, from which the story is taken, occupies a liminal space in the literary history of the Philippines, as it was published in Spain for a Spanish-reading audience, yet it is borne of her childhood in Negros, in the Philippines. The story illustrates Maria Tymoczko’s observation that postcolonial writing and interlingual translation are similar. Both are acts of representing the “foreign,” a linguistic …
The Impact Of Intellectual Capital On Earnings Management Across The Firm Life Cycle: A Study Of Manufacturing Companies Listed On The Idx From 2020 To 2023, Ashila Taqiyya Ruzami, Nanny Dewi Tanzil
The Impact Of Intellectual Capital On Earnings Management Across The Firm Life Cycle: A Study Of Manufacturing Companies Listed On The Idx From 2020 To 2023, Ashila Taqiyya Ruzami, Nanny Dewi Tanzil
Journal of Accounting Auditing and Business
This study aims to determine how each element of intellectual capital affects earnings management based on the business life cycle. The data used for this study come from manufacturing companies listed on the IDX from 2020 to 2023. Overall, the research sample consists of 121 companies. The criteria for classifying a company's life cycle are based on the company's average sales growth. This study uses panel data regression analysis through the EViews 12 application. The results conclude that all intellectual capital components negatively influence earnings management, regardless of the company's life cycle. Meanwhile, HCE has a significant negative effect at …
A Review And Meta-Analysis Of The Efficacy Of Arbuscular Mycorrhizal Fungi In Remediating Toxic Metals In Mine-Affected Soil, Sonali Banerjee, Jajati Mandal, Dibyendu Sarkar, Rupali Datta, Pradip Bhattacharyya
A Review And Meta-Analysis Of The Efficacy Of Arbuscular Mycorrhizal Fungi In Remediating Toxic Metals In Mine-Affected Soil, Sonali Banerjee, Jajati Mandal, Dibyendu Sarkar, Rupali Datta, Pradip Bhattacharyya
Michigan Tech Publications
Mines are natural reservoirs of various minerals, metals, and metalloids. Several heavy metals (HMs), such as Pb, Cd, Cr, Cu, and Ni, are major anthropogenic pollutants that cause severe environmental pollution. The accumulation of these toxic HMs in soils has raised several concerns for crop growth, food safety, and marketing. Physiological and biochemical processes in plants are severely impacted by HMs, disrupting normal metabolic activities and reducing biomass production. Phytoremediation plays a pivotal role in addressing HM contamination by offering an eco-friendly, economical, and holistic solution. Similarly, arbuscular mycorrhizal fungi (AMF) play a significant role by forming a symbiotic relationship …
Genome-Wide Association Study Reveals Shared And Distinct Genetic Architecture Of Fatty Acids And Oxylipins In The Hispanic Community Health Study/Study Of Latinos, Carolina G Downie, Heather M Highland, Mona Alotaibi, Barrett M Welch, Annie Green Howard, Susan Cheng, Nick Miller, Mohit Jain, Robert C Kaplan, Adam G Lilly, Tao Long, Tamar Sofer, Bharat Thyagarajan, Bing Yu, Kari E North, Christy L Avery
Genome-Wide Association Study Reveals Shared And Distinct Genetic Architecture Of Fatty Acids And Oxylipins In The Hispanic Community Health Study/Study Of Latinos, Carolina G Downie, Heather M Highland, Mona Alotaibi, Barrett M Welch, Annie Green Howard, Susan Cheng, Nick Miller, Mohit Jain, Robert C Kaplan, Adam G Lilly, Tao Long, Tamar Sofer, Bharat Thyagarajan, Bing Yu, Kari E North, Christy L Avery
Faculty, Staff and Student Publications
Bioactive fatty acid-derived oxylipin molecules play key roles mediating inflammation and oxidative stress. Circulating levels of fatty acids and oxylipins are influenced by environmental and genetic factors; characterizing the genetic architecture of bioactive lipids could yield new insights into underlying biology. We performed a genome-wide association study (GWAS) of 81 fatty acids and oxylipins in 11,584 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants with genetic and lipidomic data measured at study baseline (58.6% female, mean age = 46.1 years (standard deviation 13.8)). Additionally, given the effects of central obesity on inflammation, we examined interactions with waist circumference using two-degree-of-freedom …
Neoadjuvant Or Concurrent Atezolizumab With Chemoradiation For Locally Advanced Cervical Cancer: A Randomized Phase I Trial, Jyoti Mayadev, Dmitriy Zamarin, Wei Deng, Heather A. Lankes, Giulio Pesci, Hayeon Kim, Junzo P. Chino, Barbara Banbury, Ned Sherry, Elad Sharon, Sharad A. Ghamande, Catherine Ferguson, Loren Mell, Laura Holman, Cara Mathews, David O'Malley, Alexander Olawaiye, Elizabeth Hopp, Charles Leath, Larry Copeland, Robert Mannel, Roisin O'Cearbhaill, Carol Aghajanian, Russell J. Schilder
Neoadjuvant Or Concurrent Atezolizumab With Chemoradiation For Locally Advanced Cervical Cancer: A Randomized Phase I Trial, Jyoti Mayadev, Dmitriy Zamarin, Wei Deng, Heather A. Lankes, Giulio Pesci, Hayeon Kim, Junzo P. Chino, Barbara Banbury, Ned Sherry, Elad Sharon, Sharad A. Ghamande, Catherine Ferguson, Loren Mell, Laura Holman, Cara Mathews, David O'Malley, Alexander Olawaiye, Elizabeth Hopp, Charles Leath, Larry Copeland, Robert Mannel, Roisin O'Cearbhaill, Carol Aghajanian, Russell J. Schilder
Department of Medical Oncology Faculty Papers
Combined immune checkpoint blockade (ICB) and chemoradiation (CRT) is approved in patients with locally advanced cervical cancer (LACC) but optimal sequencing of CRT and ICB is unknown. NRG-GY017 (NCT03738228) was a randomized phase I trial of atezolizumab (anti-PD-L1) neoadjuvant and concurrent with CRT (Arm A) vs. concurrent with CRT (Arm B) in patients with high-risk node-positive LACC. The primary endpoint was the fraction of expanded tumor-associated T-cell receptor (TCR) clones in blood at day 21 as a surrogate measure of anti-tumor immune response. Secondary objectives were safety and feasibility, 2-year disease-free survival (DFS), and predictive value of PD-L1 expression. Forty …
Functional Characterization Of Qt Interval Associated Scn5a Enhancer Variants Identify Combined Additive Effects, Lavanya Gunamalai, Parul Singh, Brian Berg, Leilei Shi, Ernesto Sanchez, Alexa Smith, Ghislain Breton, Mark T Bedford, Darius Balciunas, Ashish Kapoor
Functional Characterization Of Qt Interval Associated Scn5a Enhancer Variants Identify Combined Additive Effects, Lavanya Gunamalai, Parul Singh, Brian Berg, Leilei Shi, Ernesto Sanchez, Alexa Smith, Ghislain Breton, Mark T Bedford, Darius Balciunas, Ashish Kapoor
Faculty, Staff and Student Publications
Several empirical and theoretical studies suggest the presence of multiple enhancers per gene that collectively regulate gene expression, and that common sequence variation impacting on the activities of these enhancers is a major source of inter-individual gene expression variability. However, for the vast majority of genes, enhancers and the underlying regulatory variation remains unknown. Even for the genes with well-characterized enhancers, the nature of the combined effects from multiple enhancers and their variants, when known, on gene expression regulation remains unexplored. Here, we have evaluated the combined effects from five SCN5A enhancers and their regulatory variants that are known to …
A Phase Ia Study Of A Novel Anti-Her2 Antibody-Drug Conjugate Gq1001 In Patients With Previously Treated Her2 Positive Advanced Solid Tumors, Chenfei Zhou, Bin Wang, Christina Teng, Hui Yang, Sarina A Piha-Paul, Gary Richardson, Ashanya Malalasekera, Yajun Sun, Wei Wang, Jieqiong Liu, Yan Shi, Xianbao Zhan, Charlotte Lemech
A Phase Ia Study Of A Novel Anti-Her2 Antibody-Drug Conjugate Gq1001 In Patients With Previously Treated Her2 Positive Advanced Solid Tumors, Chenfei Zhou, Bin Wang, Christina Teng, Hui Yang, Sarina A Piha-Paul, Gary Richardson, Ashanya Malalasekera, Yajun Sun, Wei Wang, Jieqiong Liu, Yan Shi, Xianbao Zhan, Charlotte Lemech
Faculty, Staff and Student Publications
Background: A novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate (ADC) GQ1001 was assessed in patients with previously treated HER2 positive advanced solid tumors in a global multi-center phase Ia dose escalation trial.
Methods: In this phase Ia trial, a modified 3 + 3 study design was adopted during dose escalation phase. Eligible patients were enrolled, and GQ1001 monotherapy was administered intravenously every 3 weeks. The starting dose was 1.2 mg/kg, followed by 2.4, 3.6, 4.8, 6.0, 7.2 and 8.4 mg/kg. Extra patients were enrolled into 6.0, 7.2, and 8.4 mg/kg cohorts as dose expansion phase. The primary …
Alleviation Of Liver Fibrosis By Inhibiting A Non-Canonical Atf4-Regulated Enhancer Program In Hepatic Stellate Cells, Li-Xian Yang, Chuangye Qi, Si Lu, Xiang-Shi Ye, Parnaz Merikhian, Du-Yu Zhang, Tao Yao, Jiang-Sha Zhao, Ying Wu, Yongshi Jia, Bo Shan, Jinghai Chen, Xiaozhou Mou, Jia You, Wenbo Li, Yu-Xiong Feng
Alleviation Of Liver Fibrosis By Inhibiting A Non-Canonical Atf4-Regulated Enhancer Program In Hepatic Stellate Cells, Li-Xian Yang, Chuangye Qi, Si Lu, Xiang-Shi Ye, Parnaz Merikhian, Du-Yu Zhang, Tao Yao, Jiang-Sha Zhao, Ying Wu, Yongshi Jia, Bo Shan, Jinghai Chen, Xiaozhou Mou, Jia You, Wenbo Li, Yu-Xiong Feng
Faculty, Staff and Student Publications
Liver fibrosis is a critical liver disease that can progress to more severe manifestations, such as cirrhosis, yet no effective targeted therapies are available. Here, we identify that ATF4, a master transcription factor in ER stress response, promotes liver fibrosis by facilitating a stress response-independent epigenetic program in hepatic stellate cells (HSCs). Unlike its canonical role in regulating UPR genes during ER stress, ATF4 activates epithelial-mesenchymal transition (EMT) gene transcription under fibrogenic conditions. HSC-specific depletion of ATF4 suppresses liver fibrosis in vivo. Mechanistically, TGFβ resets ATF4 to orchestrate a unique enhancer program for the transcriptional activation of pro-fibrotic EMT genes. …