Life Sciences Commons^™

Population Screening For High-Risk Patient Identification Partnership With Care-Comprehensive Assessment, Risk, And Education., Ora K Gordon, Brad Bott, Nanor Parseghian, Kimberly K Childers, Sandra Brown

Articles, Abstracts, and Reports

No abstract provided.

Multi-Cancer Early Detection Testing (Mced), Ora K Gordon, Brad Bott, Nanor Parseghian, Paul Psychogios, Kimberly K Childers, Sandra Brown

Articles, Abstracts, and Reports

No abstract provided.

Neoadjuvant Anti-Ox40 (Medi6469) Therapy In Patients With Head And Neck Squamous Cell Carcinoma Activates And Expands Antigen-Specific Tumor-Infiltrating T Cells., Rebekka Duhen, Carmen Ballesteros-Merino, Alexandra K Frye, Eric Tran, Venkatesh Rajamanickam, Shu-Ching Chang, Yoshinobu Koguchi, Carlo Bifulco, Brady Bernard, Rom Leidner, Brendan Curti, Bernard A Fox, Walter Urba, Richard Bryan Bell, Andrew D Weinberg

Articles, Abstracts, and Reports

Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. The primary endpoint was to determine safety and feasibility of the anti-OX40 neoadjuvant treatment. The secondary objective was to assess the effect of …

Immune Checkpoint Inhibitor Therapy In Hiv-Associated Merkel Cell Carcinoma: A Case Series Of 3 Patients., Song Y Park, Candice Church, Nora A Alexander, Michi M Shinohara, Kelly G Paulson, Karl D Lewis, Nancy S Lee, Paul Nghiem

Articles, Abstracts, and Reports

No abstract provided.

Prognostic Gene Expression Signatures Of Breast Cancer Are Lacking A Sensible Biological Meaning., Kalifa Manjang, Shailesh Tripathi, Olli Yli-Harja, Matthias Dehmer, Galina Glazko, Frank Emmert-Streib

Articles, Abstracts, and Reports

The identification of prognostic biomarkers for predicting cancer progression is an important problem for two reasons. First, such biomarkers find practical application in a clinical context for the treatment of patients. Second, interrogation of the biomarkers themselves is assumed to lead to novel insights of disease mechanisms and the underlying molecular processes that cause the pathological behavior. For breast cancer, many signatures based on gene expression values have been reported to be associated with overall survival. Consequently, such signatures have been used for suggesting biological explanations of breast cancer and drug mechanisms. In this paper, we demonstrate for a large …

Partial Inhibition Of Mitochondrial Complex I Ameliorates Alzheimer's Disease Pathology And Cognition In App/Ps1 Female Mice., Andrea Stojakovic, Sergey Trushin, Anthony Sheu, Layla Khalili, Su-Youne Chang, Xing Li, Trace Christensen, Jeffrey L Salisbury, Rachel E Geroux, Benjamin Gateno, Padraig J Flannery, Mrunal Dehankar, Cory C Funk, Jordan Wilkins, Anna Stepanova, Tara O'Hagan, Alexander Galkin, Jarred Nesbitt, Xiujuan Zhu, Utkarsh Tripathi, Slobodan Macura, Tamar Tchkonia, Tamar Pirtskhalava, James L Kirkland, Rachel A Kudgus, Renee A Schoon, Joel M Reid, Yu Yamazaki, Takahisa Kanekiyo, Song Zhang, Emirhan Nemutlu, Petras Dzeja, Adam Jaspersen, Ye In Christopher Kwon, Michael K Lee, Eugenia Trushina

Articles, Abstracts, and Reports

Alzheimer's Disease (AD) is a devastating neurodegenerative disorder without a cure. Here we show that mitochondrial respiratory chain complex I is an important small molecule druggable target in AD. Partial inhibition of complex I triggers the AMP-activated protein kinase-dependent signaling network leading to neuroprotection in symptomatic APP/PS1 female mice, a translational model of AD. Treatment of symptomatic APP/PS1 mice with complex I inhibitor improved energy homeostasis, synaptic activity, long-term potentiation, dendritic spine maturation, cognitive function and proteostasis, and reduced oxidative stress and inflammation in brain and periphery, ultimately blocking the ongoing neurodegeneration. Therapeutic efficacy in vivo was monitored using translational …

Integrated Genetic And Metabolic Landscapes Predict Vulnerabilities Of Temozolomide Resistant Glioblastoma Cells., Selva Rupa Christinal Immanuel, Avinash D Ghanate, Dharmeshkumar S Parmar, Ritu Yadav, Riya Uthup, Venkateswarlu Panchagnula, Anu Raghunathan

Articles, Abstracts, and Reports

Metabolic reprogramming and its molecular underpinnings are critical to unravel the duality of cancer cell function and chemo-resistance. Here, we use a constraints-based integrated approach to delineate the interplay between metabolism and epigenetics, hardwired in the genome, to shape temozolomide (TMZ) resistance. Differential metabolism was identified in response to TMZ at varying concentrations in both the resistant neurospheroidal (NSP) and the susceptible (U87MG) glioblastoma cell-lines. The genetic basis of this metabolic adaptation was characterized by whole exome sequencing that identified mutations in signaling pathway regulators of growth and energy metabolism. Remarkably, our integrated approach identified rewiring in glycolysis, TCA cycle, …

Circulating Exosomal Microrna Expression Patterns Distinguish Cardiac Sarcoidosis From Myocardial Ischemia., Elliott D Crouser, Mark W Julian, Sabahattin Bicer, Vikas Ghai, Taek-Kyun Kim, Lisa A Maier, May Gillespie, Nabeel Y Hamzeh, Kai Wang

Articles, Abstracts, and Reports

OBJECTIVE: Cardiac sarcoidosis is difficult to diagnose, often requiring expensive and inconvenient advanced imaging techniques. Circulating exosomes contain genetic material, such as microRNA (miRNA), that are derived from diseased tissues and may serve as potential disease-specific biomarkers. We thus sought to determine whether circulating exosome-derived miRNA expression patterns would distinguish cardiac sarcoidosis (CS) from acute myocardial infarction (AMI).

METHODS: Plasma and serum samples conforming to CS, AMI or disease-free controls were procured from the Biologic Specimen and Data Repository Information Coordinating Center repository and National Jewish Health. Next generation sequencing (NGS) was performed on exosome-derived total RNA (n = 10 …

Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon

Articles, Abstracts, and Reports

Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (pilot cohort; n = 92), AJCC stage III patients given adjuvant BCG (verification cohort; n = 269), and …

A Pilot Study Comparing The Efficacy Of Lactate Dehydrogenase Levels Versus Circulating Cell-Free Micrornas In Monitoring Responses To Checkpoint Inhibitor Immunotherapy In Metastatic Melanoma Patients., Matias A Bustos, Rebecca Gross, Negin Rahimzadeh, Hunter Cole, Linh T Tran, Kevin Tran, Ling Takeshima, Stacey L Stern, Steven O'Day, Dave Hoon

Articles, Abstracts, and Reports

Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients' disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients' responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA; 2083 …

An Exploratory Pilot Study With Plasma Protein Signatures Associated With Response Of Patients With Depression To Antidepressant Treatment For 10 Weeks., Eun Young Kim, Hee-Sung Ahn, Min Young Lee, Jiyoung Yu, Jeonghun Yeom, Hwangkyo Jeong, Hophil Min, Hyun Jeong Lee, Kyunggon Kim, Yong Min Ahn

Articles, Abstracts, and Reports

Major depressive disorder (MDD) is a leading cause of global disability with a chronic and recurrent course. Recognition of biological markers that could predict and monitor response to drug treatment could personalize clinical decision-making, minimize unnecessary drug exposure, and achieve better outcomes. Four longitudinal plasma samples were collected from each of ten patients with MDD treated with antidepressants for 10 weeks. Plasma proteins were analyzed qualitatively and quantitatively with a nanoflow LC-MS/MS technique. Of 1153 proteins identified in the 40 longitudinal plasma samples, 37 proteins were significantly associated with response/time and clustered into six according to time and response by …

Society For Immunotherapy Of Cancer Clinical And Biomarkers Data Sharing Resource Document: Volume I-Conceptual Challenges., Sergio Rutella, Michael A Cannarile, Sacha Gnjatic, Bruno Gomes, Justin Guinney, Vaios Karanikas, Mohan Karkada, John M Kirkwood, Beatrix Kotlan, Giuseppe V Masucci, Els Meeusen, Anne Monette, Aung Naing, Vésteinn Thorsson, Nicholas Tschernia, Ena Wang, Daniel K Wells, Timothy L Wyant, Alessandra Cesano

Articles, Abstracts, and Reports

The sharing of clinical trial data and biomarker data sets among the scientific community, whether the data originates from pharmaceutical companies or academic institutions, is of critical importance to enable the development of new and improved cancer immunotherapy modalities. Through data sharing, a better understanding of current therapies in terms of their efficacy, safety and biomarker data profiles can be achieved. However, the sharing of these data sets involves a number of stakeholder groups including patients, researchers, private industry, scientific journals and professional societies. Each of these stakeholder groups has differing interests in the use and sharing of clinical trial …

Neoantigen-Specific Cd4(+) T-Cell Response Is Critical For The Therapeutic Efficacy Of Cryo-Thermal Therapy, Peng Peng, Hong-Ming Hu, Ping Liu, Lisa X Xu

Articles, Abstracts, and Reports

Background: Traditional tumor thermal ablations, such as radiofrequency ablation (RFA) and cryoablation, can result in good local control of tumor, but traditional tumor thermal ablations are limited by poor long-term survival due to the failure of control of distal metastasis. Our previous studies developed a novel cryo-thermal therapy to treat the B16F10 melanoma mouse model. Long-term survival and T-cell-mediated durable antitumor immunity were achieved after cryo-thermal therapy, but whether tumor antigen-specific T-cells were augmented by cryo-thermal therapy was not determined.

Methods: The long-term antitumor therapeutic efficacy of cryo-thermal therapy was performed in B16F10 murine melanoma models. Splenocytes derived from mice …

Defining The Proteolytic Landscape During Enterovirus Infection., Mohsan Saeed, Sebastian Kapell, Nicholas T Hertz, Xianfang Wu, Kierstin Bell, Alison W Ashbrook, Milica Tesic Mark, Henry A Zebroski, Maxwell L Neal, Malin Flodström-Tullberg, Margaret R Macdonald, John D Aitchison, Henrik Molina, Charles M Rice

Articles, Abstracts, and Reports

Viruses cleave cellular proteins to remodel the host proteome. The study of these cleavages has revealed mechanisms of immune evasion, resource exploitation, and pathogenesis. However, the full extent of virus-induced proteolysis in infected cells is unknown, mainly because until recently the technology for a global view of proteolysis within cells was lacking. Here, we report the first comprehensive catalog of proteins cleaved upon enterovirus infection and identify the sites within proteins where the cleavages occur. We employed multiple strategies to confirm protein cleavages and assigned them to one of the two enteroviral proteases. Detailed characterization of one substrate, LSM14A, a …

Efficacy And Safety Of First-Line Avelumab In Patients With Advanced Non-Small Cell Lung Cancer: Results From A Phase Ib Cohort Of The Javelin Solid Tumor Study., Claire F Verschraegen, Guy Jerusalem, Edward F Mcclay, Nicholas Iannotti, Charles H Redfern, Jaafar Bennouna, Franklin L Chen, Karen Kelly, Janice Mehnert, John C Morris, Matthew H Taylor, David Spigel, Ding Wang, Hans Juergen Grote, Dongli Zhou, Neru Munshi, Marcis Bajars, James L Gulley

Articles, Abstracts, and Reports

INTRODUCTION: Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC).

METHODS: In a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

RESULTS: Overall, 156 patients were enrolled …

Brainstem Ischemic Syndrome In Juvenile Nf2., John W Henson, Tara Benkers, Connor Mccormick

Articles, Abstracts, and Reports

Objective: A new case of brainstem ischemic necrosis in a young woman with de novo neurofibromatosis type 2 (NF2) is reported, and given notable similarities to 7 prior cases of brainstem stroke in the literature, features defining a possible syndrome were sought.

Methods: Case review including detailed clinical assessment, neuroimaging analysis, genetic testing, and brain biopsy, followed by a multicase analysis.

Results: Brainstem ischemia in juvenile NF2 typically occurs in teenagers without previously known NF2 as an acute, monophasic presentation with restricted diffusion in the midbrain or pons following a recent hypoperfusion event, normal vascular imaging, obvious intracranial imaging features …

Meta-Analysis Of The Alzheimer's Disease Human Brain Transcriptome And Functional Dissection In Mouse Models., Ying-Wooi Wan, Rami Al-Ouran, Carl G Mangleburg, Thanneer M Perumal, Tom V Lee, Katherine Allison, Vivek Swarup, Cory C Funk, Chris Gaiteri, Mariet Allen, Minghui Wang, Sarah M Neuner, Catherine C Kaczorowski, Vivek M Philip, Gareth R Howell, Heidi Martini-Stoica, Hui Zheng, Hongkang Mei, Xiaoyan Zhong, Jungwoo Wren Kim, Valina L Dawson, Ted M Dawson, Ping-Chieh Pao, Li-Huei Tsai, Jean-Vianney Haure-Mirande, Michelle E Ehrlich, Paramita Chakrabarty, Yona Levites, Xue Wang, Eric B Dammer, Gyan Srivastava, Sumit Mukherjee, Solveig K Sieberts, Larsson Omberg, Kristen D Dang, James A Eddy, Phil Snyder, Yooree Chae, Sandeep Amberkar, Wenbin Wei, Winston Hide, Christoph Preuss, Ayla Ergun, Phillip J Ebert, David C Airey, Sara Mostafavi, Lei Yu, Hans-Ulrich Klein, Accelerating Medicines Partnership, Alzheimer’S Disease Consortium, Gregory W Carter, David A Collier, Todd E Golde, Allan I Levey, David A Bennett, Karol Estrada, T Matthew Townsend, Bin Zhang, Eric Schadt, Philip L De Jager, Nathan D Price, Nilüfer Ertekin-Taner, Zhandong Liu, Joshua M Shulman, Lara M Mangravite, Benjamin A Logsdon

Articles, Abstracts, and Reports

We present a consensus atlas of the human brain transcriptome in Alzheimer's disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington's disease, amyotrophic …

Inter-Tumor Heterogeneity-Melanomas Respond Differently To Gm-Csf-Mediated Activation., Adi Moshe, Sivan Izraely, Orit Sagi-Assif, Sapir Malka, Shlomit Ben-Menachem, Tsipi Meshel, Metsada Pasmanik-Chor, Dave Hoon, Isaac P Witz

Articles, Abstracts, and Reports

Granulocyte-monocyte colony stimulating factor (GM-CSF) is used as an adjuvant in various clinical and preclinical studies with contradictory results. These were attributed to opposing effects of GM-CSF on the immune or myeloid systems of the treated patients or to lack of optimal dosing regimens. The results of the present study point to inter-tumor heterogeneity as a possible mechanism accounting for the contrasting responses to GM-CSF incorporating therapies. Employing xenograft models of human melanomas in nude mice developed in our lab, we detected differential functional responses of melanomas from different patients to GM-CSF both in vitro as well as in vivo. …

A Phase Ii Single-Arm Study Of Pembrolizumab With Enzalutamide In Men With Metastatic Castration-Resistant Prostate Cancer Progressing On Enzalutamide Alone., Julie N Graff, Tomasz M Beer, Joshi J Alumkal, Rachel E Slottke, William L. Redmond, George V Thomas, Reid F Thompson, Mary A Wood, Yoshinobu Koguchi, Yiyi Chen, Emile Latour, Raymond C Bergan, Charles G Drake, Amy E Moran

Articles, Abstracts, and Reports

BACKGROUND: Checkpoint inhibitors can induce profound anticancer responses, but programmed cell death protein-1 (PD-1) inhibition monotherapy has shown minimal activity in prostate cancer. A published report showed that men with prostate cancer who were resistant to the second-generation androgen receptor inhibitor enzalutamide had increased programmed death-ligand 1 (PD-L1) expression on circulating antigen-presenting cells. We hypothesized that the addition of PD-1 inhibition in these patients could induce a meaningful cancer response.

METHODS: We evaluated enzalutamide plus the PD-1 inhibitor pembrolizumab in a single-arm phase II study of 28 men with metastatic castration-resistant prostate cancer (mprogressing on enzalutamide alone. Pembrolizumab 200 mg …

Advancing Human Health In The Decade Ahead: Pregnancy As A Key Window For Discovery: A Burroughs Wellcome Fund Pregnancy Think Tank., Yoel Sadovsky, Sam Mesiano, Graham J Burton, Michelle Lampl, Jeffrey C Murray, Rachel M Freathy, Anita Mahadevan-Jansen, Ashley Moffett, Nathan D Price, Paul H Wise, Derek E Wildman, Ralph Snyderman, Nigel Paneth, John Anthony Capra, Marcelo A Nobrega, Yaacov Barak, Louis J Muglia

Articles, Abstracts, and Reports

Recent revolutionary advances at the intersection of medicine, omics, data sciences, computing, epidemiology, and related technologies inspire us to ponder their impact on health. Their potential impact is particularly germane to the biology of pregnancy and perinatal medicine, where limited improvement in health outcomes for women and children has remained a global challenge. We assembled a group of experts to establish a Pregnancy Think Tank to discuss a broad spectrum of major gestational disorders and adverse pregnancy outcomes that affect maternal-infant lifelong health and should serve as targets for leveraging the many recent advances. This report reflects avenues for future …

Correction To: Small Molecule Kras Agonist For Mutant Kras Cancer Therapy., Ke Xu, Dongkyoo Park, Andrew T Magis, Jun Zhang, Wei Zhou, Gabriel L Sica, Suresh S Ramalingam, Walter J Curran, Xingming Deng

Articles, Abstracts, and Reports

An amendment to this paper has been published and can be accessed via the original article.

The Society For Immunotherapy Of Cancer Perspective On Regulation Of Interleukin-6 Signaling In Covid-19-Related Systemic Inflammatory Response, Fernanda I. Arnaldez, Steven J. O'Day, Charles G. Drake, Bernard A Fox, Bingqing Fu, Walter Urba, Vincenzo Montesarchio, Jeffrey S. Weber, Haiming Wei, Jon M. Wigginton, Paolo Antonio Ascierto

Articles, Abstracts, and Reports

The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as ‘cytokine storm’. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes …

Comparative Lipidomics Of 5-Fluorouracil-Sensitive And -Resistant Colorectal Cancer Cells Reveals Altered Sphingomyelin And Ceramide Controlled By Acid Sphingomyelinase (Smpd1)., Jae Hun Jung, Kohei Taniguchi, Hyeong Min Lee, Min Young Lee, Raju Bandu, Kazumasa Komura, Kil Yeon Lee, Yukihiro Akao, Kwang Pyo Kim

Articles, Abstracts, and Reports

5-Fluorouracil (5-FU) is a chemotherapeutic drug widely used to treat colorectal cancer. 5-FU is known to gradually lose its efficacy in treating colorectal cancer following the acquisition of resistance. We investigated the mechanism of 5-FU resistance using comprehensive lipidomic approaches. We performed lipidomic analysis on 5-FU-resistant (DLD-1/5-FU) and -sensitive (DLD-1) colorectal cancer cells using MALDI-MS and LC-MRM-MS. In particular, sphingomyelin (SM) species were significantly up-regulated in 5-FU-resistant cells in MALDI-TOF analysis. Further, we quantified sphingolipids including SM and Ceramide (Cer) using Multiple Reaction Monitoring (MRM), as they play a vital role in drug resistance. We found that 5-FU resistance in …

Memote For Standardized Genome-Scale Metabolic Model Testing., Christian Lieven, Moritz E Beber, Brett G Olivier, Frank T Bergmann, Meric Ataman, Parizad Babaei, Jennifer A Bartell, Lars M Blank, Siddharth Chauhan, Kevin Correia, Christian Diener, Andreas Dräger, Birgitta E Ebert, Janaka N Edirisinghe, José P Faria, Adam M Feist, Georgios Fengos, Ronan M T Fleming, Beatriz García-Jiménez, Vassily Hatzimanikatis, Wout Van Helvoirt, Christopher S Henry, Henning Hermjakob, Markus J Herrgård, Ali Kaafarani, Hyun Uk Kim, Zachary King, Steffen Klamt, Edda Klipp, Jasper J Koehorst, Matthias König, Meiyappan Lakshmanan, Dong-Yup Lee, Sang Yup Lee, Sunjae Lee, Nathan E Lewis, Filipe Liu, Hongwu Ma, Daniel Machado, Radhakrishnan Mahadevan, Paulo Maia, Adil Mardinoglu, Gregory L Medlock, Jonathan M Monk, Jens Nielsen, Lars Keld Nielsen, Juan Nogales, Intawat Nookaew, Bernhard O Palsson, Jason A Papin, Kiran R Patil, Mark Poolman, Nathan D Price, Osbaldo Resendis-Antonio, Anne Richelle, Isabel Rocha, Benjamín J Sánchez, Peter J Schaap, Rahuman S Malik Sheriff, Saeed Shoaie, Nikolaus Sonnenschein, Bas Teusink, Paulo Vilaça, Jon Olav Vik, Judith A H Wodke, Joana C Xavier, Qianqian Yuan, Maksim Zakhartsev, Cheng Zhang

Articles, Abstracts, and Reports

No abstract provided.

Micom: Metagenome-Scale Modeling To Infer Metabolic Interactions In The Gut Microbiota., Christian Diener, Sean M Gibbons, Osbaldo Resendis-Antonio

Articles, Abstracts, and Reports

Compositional changes in the gut microbiota have been associated with a variety of medical conditions such as obesity, Crohn's disease, and diabetes. However, connecting microbial community composition to ecosystem function remains a challenge. Here, we introduce MICOM, a customizable metabolic model of the human gut microbiome. By using a heuristic optimization approach based on L2 regularization, we were able to obtain a unique set of realistic growth rates that corresponded well with observed replication rates. We integrated adjustable dietary and taxon abundance constraints to generate personalized metabolic models for individual metagenomic samples. We applied MICOM to a balanced cohort of …

Cri Iatlas: An Interactive Portal For Immuno-Oncology Research., James A Eddy, Vésteinn Thorsson, Andrew E Lamb, David L Gibbs, Carolina Heimann, Jia Xin Yu, Verena Chung, Yooree Chae, Kristen Dang, Benjamin G Vincent, Ilya Shmulevich, Justin Guinney

Articles, Abstracts, and Reports

The Cancer Research Institute (CRI) iAtlas is an interactive web platform for data exploration and discovery in the context of tumors and their interactions with the immune microenvironment. iAtlas allows researchers to study immune response characterizations and patterns for individual tumor types, tumor subtypes, and immune subtypes. iAtlas supports computation and visualization of correlations and statistics among features related to the tumor microenvironment, cell composition, immune expression signatures, tumor mutation burden, cancer driver mutations, adaptive cell clonality, patient survival, expression of key immunomodulators, and tumor infiltrating lymphocyte (TIL) spatial maps. iAtlas was launched to accompany the release of the TCGA …

Progressive Shifts In The Gut Microbiome Reflect Prediabetes And Diabetes Development In A Treatment-Naive Mexican Cohort., Christian Diener, María De Lourdes Reyes-Escogido, Lilia M Jimenez-Ceja, Mariana Matus, Claudia M Gomez-Navarro, Nathaniel D Chu, Vivian Zhong, M Elizabeth Tejero, Eric Alm, Osbaldo Resendis-Antonio, Rodolfo Guardado-Mendoza

Articles, Abstracts, and Reports

Type 2 diabetes (T2D) is a global epidemic that affects more than 8% of the world's population and is a leading cause of death in Mexico. Diet and lifestyle are known to contribute to the onset of T2D. However, the role of the gut microbiome in T2D progression remains uncertain. Associations between microbiome composition and diabetes are confounded by medication use, diet, and obesity. Here we present data on a treatment-naive cohort of 405 Mexican individuals across varying stages of T2D severity. Associations between gut bacteria and more than 200 clinical variables revealed a defined set of bacterial genera that …

Impact Of Prevnar (Pcv13) Vaccine Recommendations In Pediatric And Immunocompetent Adults 65 Years And Older: What Are The Benefits And Risks?, James E. Watkins, Anne Marie Thibodeaux, John C. Darnell

Articles, Abstracts, and Reports

Background:

2000: PCV7 becomes the first FDA approved pneumococcal vaccine for pediatrics
2010: PCV13 recommended in pediatrics
2014: PCV13 recommended in immunocompetent adults 65+
2018: CDC looked at data since 2014 recommendation
2019: PCV13 now shared clinical decision-making

Cancer Cell Population Growth Kinetics At Low Densities Deviate From The Exponential Growth Model And Suggest An Allee Effect., Kaitlyn E Johnson, Grant Howard, William Mo, Michael K Strasser, Ernesto A B F Lima, Sui Huang, Amy Brock

Articles, Abstracts, and Reports

Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models, however, tumor growth data are limited by the …

Cancer Cell Population Growth Kinetics At Low Densities Deviate From The Exponential Growth Model And Suggest An Allee Effect., Kaitlyn E Johnson, Grant Howard, William Mo, Michael K Strasser, Ernesto A B F Lima, Sui Huang, Amy Brock

Articles, Abstracts, and Reports

Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models, however, tumor growth data are limited by the …