Digital Commons Network^™

Predicting Cancer Immunotherapy Response From Gut Microbiomes Using Machine Learning Models, Hai Liang, Jay-Hyun Jo, Zhiwei Zhang, Margaret A Macgibeny, Jungmin Han, Diana M Proctor, Monica E Taylor, You Che, Paul Juneau, Andrea B Apolo, John A Mcculloch, Diwakar Davar, Hassane M Zarour, Amiran K Dzutsev, Isaac Brownell, Giorgio Trinchieri, James L Gulley, Heidi H Kong

Faculty, Staff and Student Publications

Cancer immunotherapy has significantly improved patient survival. Yet, half of patients do not respond to immunotherapy. Gut microbiomes have been linked to clinical responsiveness of melanoma patients on immunotherapies; however, different taxa have been associated with response status with implicated taxa inconsistent between studies. We used a tumor-agnostic approach to find common gut microbiome features of response among immunotherapy patients with different advanced stage cancers. A combined meta-analysis of 16S rRNA gene sequencing data from our mixed tumor cohort and three published immunotherapy gut microbiome datasets from different melanoma patient cohorts found certain gut bacterial taxa correlated with immunotherapy response …

Characterization Of The Blood Oxygen Level Dependent Hemodynamic Response Function In Human Subcortical Regions With High Spatiotemporal Resolution, Jung Hwan Kim, Amanda J Taylor, Marc Himmelbach, Gisela E Hagberg, Klaus Scheffler, David Ress

Faculty, Staff and Student Publications

Subcortical brain regions are absolutely essential for normal human function. These phylogenetically early brain regions play critical roles in human behaviors such as the orientation of attention, arousal, and the modulation of sensory signals to cerebral cortex. Despite the critical health importance of subcortical brain regions, there has been a dearth of research on their neurovascular responses. Blood oxygen level dependent (BOLD) functional MRI (fMRI) experiments can help fill this gap in our understanding. The BOLD hemodynamic response function (HRF) evoked by brief (<4 >s) neural activation is crucial for the interpretation of fMRI results because linear analysis between neural …

Differential Gene Expression In Cord Blood Of Infants Diagnosed With Cerebral Palsy: A Pilot Analysis Of The Beam Cohort, Maria L V Dizon, Raye-Ann O Deregnier, Steven J Weiner, Michael W Varner, Dwight J Rouse, Maged M Costantine, Ronald J Wapner, John M Thorp, Sean C Blackwell, Nina K Ayala, Antonio F Saad, Steve N Caritis, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Maternal-Fetal Medicine Units Network

Faculty, Staff and Student Publications

The Beneficial Effects of Antenatal Magnesium clinical trial was conducted between 1997 and 2007, and demonstrated a significant reduction in cerebral palsy (CP) in preterm infants who were exposed to peripartum magnesium sulfate (MgSO4). However, the mechanism by which MgSO4 confers neuroprotection remains incompletely understood. Cord blood samples from this study were interrogated during an era when next-generation sequencing was not widely accessible and few gene expression differences or biomarkers were identified between treatment groups. Our goal was to use bulk RNA deep sequencing to identify differentially expressed genes comparing the following four groups: newborns who ultimately developed CP treated …

Methodologies To Unlock The Molecular Expression And Cellular Structure Of Ocular Lens Epithelial Cells, Justin Parreno, Grace Emin, Michael P Vu, Jackson T Clark, Sandeep Aryal, Shaili D Patel, Catherine Cheng

Faculty, Staff and Student Publications

The transparent ocular lens in the anterior chamber of the eye is responsible for fine focusing of light onto the retina. The lens is entirely cellular with bulk of the tissue composed of fiber cells, and the anterior hemisphere of the lens is covered by a monolayer of epithelial cells. Lens epithelial cells are important for maintaining fiber cell homeostasis and for continual growth of the lens tissue throughout life. Cataracts, defined as any opacity in the lens, remain the leading cause of blindness in the world. Following cataract surgery, lens epithelial cells can undergo a process of epithelial-to-mesenchymal transition …

Ret Signaling Pathway And Ret Inhibitors In Human Cancer, Angelina T Regua, Mariana Najjar, Hui-Wen Lo

Faculty, Staff and Student Publications

Rearranged during transfection (RET) receptor tyrosine kinase was first identified over thirty years ago as a novel transforming gene. Since its discovery and subsequent pathway characterization, RET alterations have been identified in numerous cancer types and are most prevalent in thyroid carcinomas and non-small cell lung cancer (NSCLC). In other tumor types such as breast cancer and salivary gland carcinomas, RET alterations can be found at lower frequencies. Aberrant RET activity is associated with poor prognosis of thyroid and lung carcinoma patients, and is strongly correlated with increased risk of distant metastases. RET aberrations encompass a variety of genomic or …

Dat3m: A Data Tracker For Multi-Faceted Management Of Multi-Site Clinical Research Data Submission, Curation, Master Inventorying, And Sharing, Shiqiang Tao, Licong Cui, Wei-Chun Chou, Samden Lhatoo, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Managing research data is an important and challenging aspect of clinical studies, especially for multi-site collaboratives. To address this challenge, we designed, developed and deployed a multi-faceted, multi-level interactive data tracker (DaT3M) for multi-site clinical research data submission, curation, master inventorying, and sharing. Components of DaT3M include data overview, data portal, data status panel, data query engine, and data downloader. DaT3M managed clinical research data for the Center for SUDEP Research (CSR). The CSR instance of DaT3M includes 2,743 subjects from seven data contributing institutions, 7 data modalities and 10,678 data components: 3,398 Epilepsy Monitoring Unit reports, 3,440 electroencephalography recordings, …

Deep Graph Convolutional Network For Us Birth Data Harmonization, Lishan Yu, Hamisu M Salihu, Deepa Dongarwar, Luyao Chen, Xiaoqian Jiang

Faculty, Staff and Student Publications

In this paper, we developed a feasible and efficient deep-learning-based framework to combine the United States (US) natality data for the last five decades, with changing variables and factors, into a consistent database. We constructed a graph based on the property and elements of databases, including variables, and conducted a graph convolutional network (GCN) to learn the embeddings of variables on the constructed graph, where the learned embeddings implied the similarity of variables. Specifically, we devised a loss function with a slack margin and a banlist mechanism (for a random walk) to learn the desired structure (two nodes sharing more …

Apaview: A Web-Based Platform For Alternative Polyadenylation Analyses In Hematological Cancers, Xi Hu, Jialin Song, Jacqueline Chyr, Jinping Wan, Xiaoyan Wang, Jianqiang Du, Junbo Duan, Huqin Zhang, Xiaobo Zhou, Xiaoming Wu

Faculty, Staff and Student Publications

Background: Hematologic malignancies, such as acute promyelocytic leukemia (APL) and acute myeloid leukemia (AML), are cancers that start in blood-forming tissues and can affect the blood, bone marrow, and lymph nodes. They are often caused by genetic and molecular alterations such as mutations and gene expression changes. Alternative polyadenylation (APA) is a post-transcriptional process that regulates gene expression, and dysregulation of APA contributes to hematological malignancies. RNA-sequencing-based bioinformatic methods can identify APA sites and quantify APA usages as molecular indexes to study APA roles in disease development, diagnosis, and treatment. Unfortunately, APA data pre-processing, analysis, and visualization are time-consuming, inconsistent, …

Improving Pharmacovigilance Signal Detection From Clinical Notes With Locality Sensitive Neural Concept Embeddings, Justin Mower, Elmer Bernstam, Hua Xu, Sahiti Myneni, Devika Subramanian, Trevor Cohen

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Although pharmaceutical products undergo clinical trials to profile efficacy and safety, some adverse drug reactions (ADRs) are only discovered after release to market. Post-market drug safety surveillance - pharmacovigilance - leverages information from various sources to proactively identify such ADRs. Clinical notes are one source of observational data that could assist this process, but their inherent complexity can obfuscate possible ADR signals. In previous research, embeddings trained on observational reports have improved detection of such signals over commonly used statistical measures. Moreover, neural embedding methods which further encode juxtapositional information have shown promise on analogical retrieval tasks, suggesting proximity-based alternatives …

Brain Antigens Stimulate Proliferation Of T Lymphocytes With A Pathogenic Phenotype In Multiple Sclerosis Patients, Assaf Gottlieb, Hoai Phuong T Pham, John William Lindsey

Faculty, Staff and Student Publications

A method to stimulate T lymphocytes with a broad range of brain antigens would facilitate identification of the autoantigens for multiple sclerosis and enable definition of the pathogenic mechanisms important for multiple sclerosis. In a previous work, we found that the obvious approach of culturing leukocytes with homogenized brain tissue does not work because the brain homogenate suppresses antigen-specific lymphocyte proliferation. We now report a method that substantially reduces the suppressive activity. We used this non-suppressive brain homogenate to stimulate leukocytes from multiple sclerosis patients and controls. We also stimulated with common viruses for comparison. We measured proliferation, selected the …

A Multimodal Clinical Data Resource For Personalized Risk Assessment Of Sudden Unexpected Death In Epilepsy, Xiaojin Li, Shiqiang Tao, Samden D Lhatoo, Licong Cui, Yan Huang, Johnson P Hampson, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Epilepsy affects ~2–3 million individuals in the United States, a third of whom have uncontrolled seizures. Sudden unexpected death in epilepsy (SUDEP) is a catastrophic and fatal complication of poorly controlled epilepsy and is the primary cause of mortality in such patients. Despite its huge public health impact, with a ~1/1,000 incidence rate in persons with epilepsy, it is an uncommon enough phenomenon to require multi-center efforts for well-powered studies. We developed the Multimodal SUDEP Data Resource (MSDR), a comprehensive system for sharing multimodal epilepsy data in the NIH funded Center for SUDEP Research. The MSDR aims at accelerating research …

Dose Accumulation For Mr-Guided Adaptive Radiotherapy: From Practical Considerations To State-Of-The-Art Clinical Implementation, Brigid A Mcdonald, Cornel Zachiu, John Christodouleas, Mohamed A Naser, Mark Ruschin, Jan-Jakob Sonke, Daniela Thorwarth, Daniel Létourneau, Neelam Tyagi, Tony Tadic, Jinzhong Yang, X Allen Li, Uffe Bernchou, Daniel E Hyer, Jeffrey E Snyder, Edyta Bubula-Rehm, Clifton D Fuller, Kristy K Brock

Faculty, Staff and Student Publications

MRI-linear accelerator (MR-linac) devices have been introduced into clinical practice in recent years and have enabled MR-guided adaptive radiation therapy (MRgART). However, by accounting for anatomical changes throughout radiation therapy (RT) and delivering different treatment plans at each fraction, adaptive radiation therapy (ART) highlights several challenges in terms of calculating the total delivered dose. Dose accumulation strategies-which typically involve deformable image registration between planning images, deformable dose mapping, and voxel-wise dose summation-can be employed for ART to estimate the delivered dose. In MRgART, plan adaptation on MRI instead of CT necessitates additional considerations in the dose accumulation process because MRI …

Temporal Cohort Logic, Guo-Qiang Zhang, Xiaojin Li, Yan Huang, Licong Cui

Faculty, Staff and Student Publications

We introduce a new logic, called Temporal Cohort Logic (TCL), for cohort specification and discovery in clinical and population health research. TCL is created to fill a conceptual gap in formalizing temporal reasoning in biomedicine, in a similar role that temporal logics play for computer science and its applications. We provide formal syntax and semantics for TCL and illustrate the various logical constructs using examples related to human health. Relationships and distinctions with existing temporal logical frameworks are discussed. Applications in electronic health record (EHR) and in neurophysiological data resource are provided. Our approach differs from existing temporal logics, in …

Causal Inference Of Genetic Variants And Genes In Amyotrophic Lateral Sclerosis, Siyu Pan, Xinxuan Liu, Tianzi Liu, Zhongming Zhao, Yulin Dai, Yin-Ying Wang, Peilin Jia, Fan Liu

Faculty, Staff and Student Publications

Amyotrophic lateral sclerosis (ALS) is a fatal progressive multisystem disorder with limited therapeutic options. Although genome-wide association studies (GWASs) have revealed multiple ALS susceptibility loci, the exact identities of causal variants, genes, cell types, tissues, and their functional roles in the development of ALS remain largely unknown. Here, we reported a comprehensive post-GWAS analysis of the recent large ALS GWAS (n = 80,610), including functional mapping and annotation (FUMA), transcriptome-wide association study (TWAS), colocalization (COLOC), and summary data-based Mendelian randomization analyses (SMR) in extensive multi-omics datasets. Gene property analysis highlighted inhibitory neuron 6, oligodendrocytes, and GABAergic neurons (Gad1/Gad2) as …

Cross-Talk Between Histone Methyltransferases And Demethylases Regulate Rest Transcription During Neurogenesis, Jyothishmathi Swaminathan, Shinji Maegawa, Shavali Shaik, Ajay Sharma, Javiera Bravo-Alegria, Lei Guo, Lin Xu, Arif Harmanci, Vidya Gopalakrishnan

Faculty, Staff and Student Publications

The RE1 Silencing Transcription Factor (REST) is a major regulator of neurogenesis and brain development. Medulloblastoma (MB) is a pediatric brain cancer characterized by a blockade of neuronal specification. REST gene expression is aberrantly elevated in a subset of MBs that are driven by constitutive activation of sonic hedgehog (SHH) signaling in cerebellar granular progenitor cells (CGNPs), the cells of origin of this subgroup of tumors. To understand its transcriptional deregulation in MBs, we first studied control of Rest gene expression during neuronal differentiation of normal mouse CGNPs. Higher Rest expression was observed in proliferating CGNPs compared to differentiating neurons. …

Racial And Socioeconomic Disparities In Patients With Meningioma: A Retrospective Cohort Study, Hudin N Jackson, Caroline C Hadley, A Basit Khan, Ron Gadot, James C Bayley, Arya Shetty, Jacob Mandel, Ali Jalali, K Kelly Gallagher, Alex D Sweeney, Arif O Harmanci, Akdes S Harmanci, Tiemo Klisch, Shankar P Gopinath, Ganesh Rao, Daniel Yoshor, Akash J Patel

Faculty, Staff and Student Publications

BACKGROUND: Meningiomas are the most common intracranial neoplasms. Although genomic analysis has helped elucidate differences in survival, there is evidence that racial disparities may influence outcomes. African Americans have a higher incidence of meningiomas and poorer survival outcomes. The etiology of these disparities remains unclear, but may include a combination of pathophysiology and other factors.

OBJECTIVE: To determine factors that contribute to different clinical outcomes in racial populations.

METHODS: We retrospectively reviewed 305 patients who underwent resection for meningiomas at a single tertiary care facility. We used descriptive statistics and univariate, multivariable, and Kaplan-Meier analyses to study clinical, radiographical, and …

Facilitating Federated Genomic Data Analysis By Identifying Record Correlations While Ensuring Privacy, Leonard Dervishi, Xinyue Wang, Wentao Li, Anisa Halimi, Jaideep Vaidya, Xiaoqian Jiang, Erman Ayday

Faculty, Staff and Student Publications

With the reduction of sequencing costs and the pervasiveness of computing devices, genomic data collection is continually growing. However, data collection is highly fragmented and the data is still siloed across different repositories. Analyzing all of this data would be transformative for genomics research. However, the data is sensitive, and therefore cannot be easily centralized. Furthermore, there may be correlations in the data, which if not detected, can impact the analysis. In this paper, we take the first step towards identifying correlated records across multiple data repositories in a privacy-preserving manner. The proposed framework, based on random shuffling, synthetic record …

Caries Risk Documentation And Prevention: Emeasures For Dental Electronic Health Records, Suhasini Bangar, Ana Neumann, Joel M White, Alfa Yansane, Todd R Johnson, Gregory W Olson, Shwetha V Kumar, Krishna K Kookal, Aram Kim, Enihomo Obadan-Udoh, Elizabeth Mertz, Kristen Simmons, Joanna Mullins, Ryan Brandon, Muhammad F Walji, Elsbeth Kalenderian

Faculty, Staff and Student Publications

BACKGROUND: Longitudinal patient level data available in the electronic health record (EHR) allows for the development, implementation, and validations of dental quality measures (eMeasures).

OBJECTIVE: We report the feasibility and validity of implementing two eMeasures. The eMeasures determined the proportion of patients receiving a caries risk assessment (eCRA) and corresponding appropriate risk-based preventative treatments for patients at elevated risk of caries (appropriateness of care [eAoC]) in two academic institutions and one accountable care organization, in the 2019 reporting year.

METHODS: Both eMeasures define the numerator and denominator beginning at the patient level, populations' specifications, and validated the automated queries. For …

Predicting Clinical Response To Everolimus In Er+ Breast Cancers Using Machine-Learning, Aritro Nath, Patrick A Cosgrove, Jeffrey T Chang, Andrea H Bild

Faculty, Staff and Student Publications

Endocrine therapy remains the primary treatment choice for ER+ breast cancers. However, most advanced ER+ breast cancers ultimately develop resistance to endocrine. This acquired resistance to endocrine therapy is often driven by the activation of the PI3K/AKT/mTOR signaling pathway. Everolimus, a drug that targets and inhibits the mTOR complex has been shown to improve clinical outcomes in metastatic ER+ breast cancers. However, there are no biomarkers currently available to guide the use of everolimus in the clinic for progressive patients, where multiple therapeutic options are available. Here, we utilized gene expression signatures from 9 ER+ breast cancer cell lines and …

Metabolic Imaging Using Hyperpolarization For Assessment Of Premalignancy, Shivanand Pudakalakatti, Priyank Raj, Travis C Salzillo, José S Enriquez, Dontrey Bourgeois, Prasanta Dutta, Mark Titus, Shayan Shams, Priya Bhosale, Michael Kim, Florencia Mcallister, Pratip K Bhattacharya

Faculty, Staff and Student Publications

There is an unmet need for noninvasive surrogate markers that can help identify premalignant lesions across different tumor types. Here we describe the methodology and technical details of protocols employed for in vivo

Advances In Non-Invasive Biosensing Measures To Monitor Wound Healing Progression, Walker D Short, Oluyinka O Olutoye, Benjamin W Padon, Umang M Parikh, Daniel Colchado, Hima Vangapandu, Shayan Shams, Taiyun Chi, Jangwook P Jung, Swathi Balaji

Faculty, Staff and Student Publications

Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition and wound healing include lack of bacterial contamination, good tissue perfusion, and reduced mechanical injury and …

Leveraging Deep Learning-Based Segmentation And Contours-Driven Deformable Registration For Dose Accumulation In Abdominal Structures, Molly M Mcculloch, Guillaume Cazoulat, Stina Svensson, Sergii Gryshkevych, Bastien Rigaud, Brian M Anderson, Ezgi Kirimli, Brian De, Ryan T Mathew, Mohamed Zaid, Dalia Elganainy, Christine B Peterson, Peter Balter, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

PURPOSE: Discrepancies between planned and delivered dose to GI structures during radiation therapy (RT) of liver cancer may hamper the prediction of treatment outcomes. The purpose of this study is to develop a streamlined workflow for dose accumulation in a treatment planning system (TPS) during liver image-guided RT and to assess its accuracy when using different deformable image registration (DIR) algorithms.

MATERIALS AND METHODS: Fifty-six patients with primary and metastatic liver cancer treated with external beam radiotherapy guided by daily CT-on-rails (CTOR) were retrospectively analyzed. The liver, stomach and duodenum contours were auto-segmented on all planning CTs and daily CTORs …

The Potential Of Biology-Guided Radiation Therapy In Thoracic Cancer: A Preliminary Treatment Planning Study, Steven N Seyedin, Rostem Bassalow, Osama R Mawlawi, Lehendrick M Turner, Roshal R Patel, Samuel R Mazin, Oluwaseyi M Oderinde, Yevgen Voronenko, Cody A Wages, Peter D Olcott, Joe Y Chang, Peter A Balter, James W Welsh

Faculty, Staff and Student Publications

PURPOSE: We investigated the feasibility of biology-guided radiotherapy (BgRT), a technique that utilizes real-time positron emission imaging to minimize tumor motion uncertainties, to spare nearby organs at risk.

METHODS: Volumetric modulated arc therapy (VMAT), intensity-modulated proton (IMPT) therapy, and BgRT plans were created for a paratracheal node recurrence (case 1; 60 Gy in 10 fractions) and a primary peripheral left upper lobe adenocarcinoma (case 2; 50 Gy in four fractions).

RESULTS: For case 1, BgRT produced lower bronchus V40 values compared to VMAT and IMPT. For case 2, total lung V20 was lower in the BgRT case compared to VMAT …

A Transgenic Bacterial Artificial Chromosome Approach To Identify Regulatory Regions That Direct Amhr2 And Osterix Expression In Müllerian Duct Mesenchyme, Malcolm M Moses, Rachel D Mullen, Daniel I Idowu, Peter Maye, Soazik P Jamin, Richard R Behringer

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A transgenic mouse approach using bacterial artificial chromosomes (BAC) was used to identify regulatory regions that direct Müllerian duct expression for Amhr2 and Osterix (Osx, also known as Sp7). Amhr2 encodes the receptor that mediates anti-Müllerian hormone (AMH) signaling for Müllerian duct regression in male embryos. Amhr2 is expressed in the Müllerian duct mesenchyme of both male and female embryos. A ∼147-kb BAC clone containing the Amhr2 locus was used to generate transgenic mice. The transgene was able to rescue the block in Müllerian duct regression of Amhr2-null males, suggesting that the BAC clone contains regulatory …

Genetic Variants Associated With Circulating Liver Injury Markers In Mexican Americans, A Population At Risk For Non-Alcoholic Fatty Liver Disease, Caroline M Sabotta, Suet-Ying Kwan, Lauren E Petty, Jennifer E Below, Aron Joon, Peng Wei, Susan P Fisher-Hoch, Joseph B Mccormick, Laura Beretta

Faculty, Staff and Student Publications

Objective: Mexican Americans are disproportionally affected by non-alcoholic fatty liver disease (NAFLD), liver fibrosis and hepatocellular carcinoma. Noninvasive means to identify those in this population at high risk for these diseases are urgently needed. Approach: The Cameron County Hispanic Cohort (CCHC) is a population-based cohort with high rates of obesity (51%), type 2 diabetes (28%) and NAFLD (49%). In a subgroup of 564 CCHC subjects, we evaluated 339 genetic variants previously reported to be associated with liver injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in United Kingdom and Japanese cohorts. Results: Association was confirmed for 86 variants. Among …

Automated Identification Of Missing Is-A Relations In The Human Phenotype Ontology, Maryamsadat Mohtashamian, Ran Hu, Rashmie Abeysinghe, Xubing Hao, Hua Xu, Licong Cui

Faculty, Staff and Student Publications

Auditing the Human Phenotype Ontology (HPO) is necessary to provide accurate terminology for its use in clinical research. We investigate an approach leveraging the lexical features of concepts in HPO to identify missing IS-A relations among HPO concepts. We first model the names of HPO concepts as sets of words in lower case. Then, we generate two types of concept-pairs which have at least a single common word: (1) Linked concept-pairs generated from concept-pairs having an IS-A relation; (2) Unlinked concept-pairs generated from concept-pairs without an IS- A relation. Concept-pairs generate Derived Term Pairs (DTPs) emphasizing unique lexical information of …

Magi1 Inhibits Interferon Signaling To Promote Influenza A Infection, Yin Wang, Jun-Ichi Abe, Khanh M Chau, Yongxing Wang, Hang Thi Vu, Loka Reddy Velatooru, Fahad Gulraiz, Masaki Imanishi, Venkata S K Samanthapudi, Minh T H Nguyen, Kyung Ae Ko, Ling-Ling Lee, Tamlyn N Thomas, Elizabeth A Olmsted-Davis, Sivareddy Kotla, Keigi Fujiwara, John P Cooke, Di Zhao, Scott E Evans, Nhat-Tu Le

Faculty, Staff and Student Publications

We have shown that membrane-associated guanylate kinase with inverted domain structure-1 (MAGI1), a scaffold protein with six PSD95/DiscLarge/ZO-1 (PDZ) domains, is involved in the regulation of endothelial cell (EC) activation and atherogenesis in mice. In addition to causing acute respiratory disease, influenza A virus (IAV) infection plays an important role in atherogenesis and triggers acute coronary syndromes and fatal myocardial infarction. Therefore, the aim of this study is to investigate the function and regulation of MAGI1 in IAV-induced EC activation. Whereas, EC infection by IAV increases MAGI1 expression, MAGI1 depletion suppresses IAV infection, suggesting that the induction of MAGI1 may …

Regulation Of T Cell Function By Protein S-Acylation, Savannah J West, Darren Boehning, Askar M Akimzhanov

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S-acylation, the reversible lipidation of free cysteine residues with long-chain fatty acids, is a highly dynamic post-translational protein modification that has recently emerged as an important regulator of the T cell function. The reversible nature of S-acylation sets this modification apart from other forms of protein lipidation and allows it to play a unique role in intracellular signal transduction. In recent years, a significant number of T cell proteins, including receptors, enzymes, ion channels, and adaptor proteins, were identified as S-acylated. It has been shown that S-acylation critically contributes to their function by regulating protein localization, stability and protein-protein interactions. …

Morphological Description Of Laevicaulisstuhlmanni (Simroth, 1895) (Pulmonata, Veronicellidae) From Egypt, Reham Fathey Ali, David G Robinson, Fabio Liberto

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BACKGROUND: Terrestrial slugs and snails are increasingly becoming serious pests of agricultural, horticultural and ornamental plants in Egypt, resulting in major economic losses.

NEW INFORMATION: This paper provides a detailed morphological and anatomical description of the veronicellid slug Laevicaulisstuhlmanni (Simroth, 1895) that has been recently recorded from Egypt. This population from Egypt is compared with Laevicaulis populations recently reported and described from Libya as L.striatus (Simroth, 1896) and with available data in literature. Some notes and a distribution map of the veronicellids introduced in north-eastern Africa are provided.

Impact Of Psychosocial, Behavioral And Lifestyle Factors On Subjective Cognitive Complaints And Perceived Quality Of Life In A Large Cohort Of Italian Breast Cancer Patients, Thomas West, Corrado Cavallero, Rita Ceccherini, Silva Foladore, Daniele Generali, Francesco Versace, Bruna Scaggiante

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The impact of psychosocial and behavioral factors on Cancer Related Cognitive Impairment manifestations is still under debate. Study's purpose is to determine the prevalence rate of cancer related cognitive impairment in a cohort of Italian breast cancer patients and to evaluate the implication of specific behavioral factors. For these purposes, a total of 233 women (106 breast cancer patients and 127 age-matched controls without oncological diagnosis) completed a questionnaire investigating cognitive functionality (FACT-Cog v3.0), sociodemographic characteristics, clinical information, psychosocial and behavioral factors (cognitive reserve, sleep quality, dietary habits, physical activity). The results indicated a higher prevalence rate of subjective cognitive …