Author: "Jaime Rodriguez" - Searchworks@Jio Institute Digital Library Search Results

880 results on '"Jaime Rodriguez"'

1. Molecular classification and biomarkers of outcome with immunotherapy in extensive-stage small-cell lung cancer: analyses of the CASPIAN phase 3 study

Author: Mingchao Xie, Miljenka Vuko, Jaime Rodriguez-Canales, Johannes Zimmermann, Markus Schick, Cathy O’Brien, Luis Paz-Ares, Jonathan W. Goldman, Marina Chiara Garassino, Carl M. Gay, John V. Heymach, Haiyi Jiang, J. Carl Barrett, Ross A. Stewart, Zhongwu Lai, Lauren A. Byers, Charles M. Rudin, and Yashaswi Shrestha
Subjects: Antigen presentation machinery, Biomarkers, CTLA-4, Gene expression profiling, Molecular subtyping, PD-L1, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background We explored potential predictive biomarkers of immunotherapy response in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with durvalumab (D) + tremelimumab (T) + etoposide-platinum (EP), D + EP, or EP in the randomized phase 3 CASPIAN trial. Methods 805 treatment-naïve patients with ES-SCLC were randomized (1:1:1) to receive D + T + EP, D + EP, or EP. The primary endpoint was overall survival (OS). Patients were required to provide an archived tumor tissue block (or ≥ 15 newly cut unstained slides) at screening, if these samples existed. After assessment for programmed cell death ligand-1 expression and tissue tumor mutational burden, residual tissue was used for additional molecular profiling including by RNA sequencing and immunohistochemistry. Results In 182 patients with transcriptional molecular subtyping, OS with D ± T + EP was numerically highest in the SCLC-inflamed subtype (n = 10, median 24.0 months). Patients derived benefit from immunotherapy across subtypes; thus, additional biomarkers were investigated. OS benefit with D ± T + EP versus EP was greater with high versus low CD8A expression/CD8 cell density by immunohistochemistry, but with no additional benefit with D + T + EP versus D + EP. OS benefit with D + T + EP versus D + EP was associated with high expression of CD4 (median 25.9 vs. 11.4 months) and antigen-presenting and processing machinery (25.9 vs. 14.6 months) and MHC I and II (23.6 vs. 17.3 months) gene signatures, and with higher MHC I expression by immunohistochemistry. Conclusions These findings demonstrate the tumor microenvironment is important in mediating better outcomes with D ± T + EP in ES-SCLC, with canonical immune markers associated with hypothesized immunotherapy mechanisms of action defining patient subsets that respond to D ± T. Trial registration ClinicalTrials.gov, NCT03043872.
Published: 2024
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2. 1511 Pan-tumor harmonization of pathologic response assessment for standardized data collection in neoadjuvant IO trials (PATHdata): Interim analysis of a multi-institutional reproducibility study

Author: Xiaowei Xu, Hao Wang, Michael Tetzlaff, James Ziai, Sabina Signoretti, Ashley Cimino-Mathews, Tricia Cottrell, Janis M Taube, Annikka Weissferdt, Richard A Scolyer, Pierre-Olivier Fiset, Jaime Rodriguez-Canales, Lynette M Sholl, Julie S Deutsch, Krista Chen, Carlos E de Andrea, Christine Orr, Salgado Roberto, Christian Schurch, Raja Seethala, and Alexander S Baras
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2023
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3. 1505 Spatial profiling of the SCLC tumor microenvironment defined by high MHC-I expression reveals association with functionally relevant antigen presentation

Author: Guenter Schmidt, Nicolas Brieu, Harald Hessel, Andreas Spitzmüller, Jaime Rodriguez Canales, Helen Angell, Markus Schick, Mingchao Xie, Mari Heininen-Brown, Miljenka Vuko, Monica Azqueta Gavaldon, Felix Segerer, Marco Testori, Michael Surace, Shashank Saran, Hadassah Sade, J Carl Barrett, Giulia Fabbri, and Alma Andoni
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2023
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4. Antibiotic resistance and consumption before and during the COVID-19 pandemic in Valle del Cauca, Colombia

Author: Isabel Cristina Hurtado, Sandra Valencia, Elisa Maria Pinzon, Maria Cristina Lesmes, Mauro Sanchez, Jaime Rodriguez, Brindis Ochoa, Hemant Deepak Shewade, Jeffrey K. Edwards, Katrina Hann, and Mohammed Khogali
Subjects: drug resistance, microbial, anti-bacterial agents/therapeutic use, covid-19, colombia, Medicine, Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract: Objective. To assess changes in antibiotic resistance of eight of the World Health Organization priority bug-drug combinations and consumption of six antibiotics (ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, vancomycin) before (March 2018 to July 2019) and during (March 2020 to July 2021) the COVID-19 pandemic in 31 hospitals in Valle del Cauca, Colombia. Methods. This was a before/after study using routinely collected data. For antibiotic consumption, daily defined doses (DDD) per 100 bed-days were compared. Results. There were 23 405 priority bacterial isolates with data on antibiotic resistance. The total number of isolates increased from 9 774 to 13 631 in the periods before and during the pandemic, respectively. While resistance significantly decreased for four selected bug-drug combinations (Klebsiella pneumoniae, extended spectrum beta lactamase [ESBL]-producing, 32% to 24%; K. pneumoniae, carbapenem-resistant, 4% to 2%; Pseudomonas aeruginosa, carbapenem-resistant, 12% to 8%; Acinetobacter baumannii, carbapenem-resistant, 23% to 9%), the level of resistance for Enterococcus faecium to vancomycin significantly increased (42% to 57%). There was no change in resistance for the remaining three combinations (Staphylococcus aureus, methicillin-resistant; Escherichia coli, ESBL-producing; E. coli, carbapenem-resistant). Consumption of all antibiotics increased. However, meropenem consumption decreased in intensive care unit settings (8.2 to 7.1 DDD per 100 bed-days). Conclusions. While the consumption of antibiotics increased, a decrease in antibiotic resistance of four bug-drug combinations was observed during the pandemic. This was possibly due to an increase in community-acquired infections. Increasing resistance of E. faecium to vancomycin must be monitored. The findings of this study are essential to inform stewardship programs in hospital settings of Colombia and similar contexts elsewhere.
Published: 2023
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5. Loss of ubiquitin-specific peptidase 18 destabilizes 14-3-3ζ protein and represses lung cancer metastasis

Author: Zibo Chen, Lin Zheng, Yulong Chen, Xiuxia Liu, Masanori Kawakami, Lisa Maria Mustachio, Jason Roszik, Katherine V. Ferry-Galow, Ralph E. Parchment, Xin Liu, Thorkell Andresson, Gerard Duncan, Jonathan M. Kurie, Jaime Rodriguez-Canales, Xi Liu, and Ethan Dmitrovsky
Subjects: deubiquitinase, usp18, 14-3-3ζ, lung cancer and metastasis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Cancer metastasis is a major cause of cancer-related mortality. Strategies to reduce metastases are needed especially in lung cancer, the most common cause of cancer mortality. We previously reported increased ubiquitin-specific peptidase 18 (USP18) expression in lung and other cancers. Engineered reduction of USP18 expression repressed lung cancer growth and promoted apoptosis. This deubiquitinase (DUB) stabilized targeted proteins by removing the complex interferon-stimulated gene 15 (ISG15). This study explores if the loss of USP18 reduced lung cancer metastasis. USP18 knock-down in lung cancer cells was independently achieved using small hairpin RNAs (shRNAs) and small interfering RNAs (siRNAs). USP18 knock-down reduced lung cancer growth, wound-healing, migration, and invasion versus controls (P
Published: 2022
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6. An in vivo functional genomics screen of nuclear receptors and their co-regulators identifies FOXA1 as an essential gene in lung tumorigenesis

Author: Suzie K. Hight, Allison Mootz, Rahul K. Kollipara, Elizabeth McMillan, Paul Yenerall, Yoichi Otaki, Long-Shan Li, Kimberley Avila, Michael Peyton, Jaime Rodriguez-Canales, Barbara Mino, Pamela Villalobos, Luc Girard, Patrick Dospoy, Jill Larsen, Michael A. White, John V. Heymach, Ignacio I. Wistuba, Ralf Kittler, and John D. Minna
Subjects: Non-small cell lung cancer, FOXA1, NKX2-1, Pooled shRNA screens, Xenograft, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Using a mini-library of 1062 lentiviral shRNAs targeting 40 nuclear hormone receptors and 70 of their co-regulators, we searched for potential therapeutic targets that would be important during in vivo tumor growth using a parallel in vitro and in vivo shRNA screening strategy in the non-small cell lung cancer (NSCLC) line NCI-H1819. We identified 21 genes essential for in vitro growth, and nine genes specifically required for tumor survival in vivo, but not in vitro: NCOR2, FOXA1, HDAC1, RXRA, RORB, RARB, MTA2, ETV4, and NR1H2. We focused on FOXA1, since it lies within the most frequently amplified genomic region in lung adenocarcinomas. We found that 14q-amplification in NSCLC cell lines was a biomarker for FOXA1 dependency for both in vivo xenograft growth and colony formation, but not mass culture growth in vitro. FOXA1 knockdown identified genes involved in electron transport among the most differentially regulated, indicating FOXA1 loss may lead to a decrease in cellular respiration. In support of this, FOXA1 amplification was correlated with increased sensitivity to the complex I inhibitor phenformin. Integrative ChipSeq analyses reveal that FOXA1 functions in this genetic context may be at least partially independent of NKX2-1. Our findings are consistent with a neomorphic function for amplified FOXA1, driving an oncogenic transcriptional program. These data provide new insight into the functional consequences of FOXA1 amplification in lung adenocarcinomas, and identify new transcriptional networks for exploration of therapeutic vulnerabilities in this patient population.
Published: 2020
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7. ISA101 and nivolumab for HPV-16+ cancer: updated clinical efficacy and immune correlates of response

Author: Jing Wang, Lei Feng, Qi Wang, Erminia Massarelli, Renata Ferrarotto, Michael A Curran, Jack Lee, Ignacio Wistuba, Cornelis J M Melief, Bonnie S Glisson, Kimal Rajapakshe, Cristian Coarfa, William William, Luana Guimaraes de Sousa, Jaime Rodriguez Canales, Renee L Chin, Tomas Z Barrese, and Faye M Johnson
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background The combination of ISA101, a human papilloma virus (HPV) 16 peptide vaccine, and nivolumab showed a promising response rate of 33% in patients with incurable HPV-16+ cancer. Here we report long-term clinical outcomes and immune correlates of response.Methods Patients with advanced HPV-16+ cancer and less than two prior regimens for recurrence were enrolled to receive ISA101 (100 µg/peptide) on days 1, 22, and 50 and nivolumab 3 mg/kg every 2 weeks beginning day 8 for up to 1 year. Baseline tumor samples were stained with multiplex immunofluorescence for programmed death-ligand 1 (PD-L1), programmed cell death protein-1 (PD-1), CD3, CD8, CD68, and pan-cytokeratin in a single panel and scanned with the Vectra 3.0 multispectral microscope. Whole transcriptome analysis of baseline tumors was performed with Affymetrix Clariom D arrays. Differential gene expression analysis was performed on responders versus non-responders.Results Twenty-four patients were followed for a median of 46.5 months (95% CI, 46.0 months to not reached (NR)). The median duration of response was 11.2 months (95% CI, 8.51 months to NR); three out of eight (38%) patients with objective response were without progression at 3 years. The median and 3-year overall survival were 15.3 months (95% CI, 10.6 months to 27.2 months) and 12.5% (95% CI, 4.3% to 36%), respectively. The scores for activated T cells ((CD3+PD-1+)+(CD3+CD8+PD-1+)), activated cytotoxic T cells (CD3+CD8+PD-1+), and total macrophage ((CD68+PD-L1−)+(CD68+PD-L1+)) in tumor were directly correlated with clinical response (p
Published: 2022
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8. PhasIR: An Instrumentation and Analysis Software for High-throughput Phase Transition Temperature Measurements

Author: Jaime Rodriguez, Maria Politi, Sage Scheiwiller, Shrilakshmi Bonageri, Stuart Adler, David Beck, and Lilo D. Pozzo
Subjects: high-throughput experimentation, thermal analysis, thermal imaging, melting point determination, deep-eutectic solvents, Computer engineering. Computer hardware, TK7885-7895
Abstract: We have designed an open-source and high-throughput thermal analysis system for fast and accurate estimation of phase transition temperatures for up to 96 samples analyzed simultaneously. The results are comparable to current state of the art systems such as differential scanning calorimetry (DSC), which is costly and time-consuming. The PhasIR hardware system utilizes an infrared camera to optically record thermal processes that result from the melting/freezing and/or evaporation of samples, while the accompanying open-source software package allows for subsequent batch analysis and processing to extract phase transition temperatures. The PhasIR system showed good agreement with DSC results for both pure substances and mixtures, such as deep eutectic solvents (DES). The all-in-one hardware and software system can be easily replicated and built using relatively inexpensive components at a total estimated cost of $1,080 USD. Implementation of the PhasIR system will allow for increased throughput in material thermal characterization and broader investigation of material design spaces. Metadata Overview Main design files: https://github.com/pozzo-research-group/phasIR Target group: Scientists requiring high-throughput thermal analysis of organic samples (e.g. pharmaceuticals, polymers, food ingredients, greases, solvents). Skills required: CNC machining, 3D printing, basic electronics and programming. Replication: No builds known to the authors so far.
Published: 2021
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9. SLFN11 captures cancer-immunity interactions associated with platinum sensitivity in high-grade serous ovarian cancer

Author: Claudia Winkler, Matthew King, Julie Berthe, Domenico Ferraioli, Anna Garuti, Federica Grillo, Jaime Rodriguez-Canales, Lorenzo Ferrando, Nicolas Chopin, Isabelle Ray-Coquard, Oona Delpuech, Darawan Rinchai, Davide Bedognetti, Alberto Ballestrero, Elisabetta Leo, and Gabriele Zoppoli
Subjects: Cell biology, Oncology, Medicine
Abstract: Large independent analyses on cancer cell lines followed by functional studies have identified Schlafen 11 (SLFN11), a putative helicase, as the strongest predictor of sensitivity to DNA-damaging agents (DDAs), including platinum. However, its role as a prognostic biomarker is undefined, partially due to the lack of validated methods to score SLFN11 in human tissues. Here, we implemented a pipeline to quantify SLFN11 in human cancer samples. By analyzing a cohort of high-grade serous ovarian carcinoma (HGSOC) specimens before platinum-based chemotherapy treatment, we show, for the first time to our knowledge, that SLFN11 density in both the neoplastic and microenvironmental components was independently associated with favorable outcome. We observed SLFN11 expression in both infiltrating innate and adaptive immune cells, and analyses in a second, independent, cohort revealed that SLFN11 was associated with immune activation in HGSOC. We found that platinum treatments activated immune-related pathways in ovarian cancer cells in an SLFN11-dependent manner, representative of tumor-immune transactivation. Moreover, SLFN11 expression was induced in activated, isolated immune cell subpopulations, hinting that SLFN11 in the immune compartment may be an indicator of immune transactivation. In summary, we propose SLFN11 is a dual biomarker capturing simultaneously interconnected immunological and cancer cell–intrinsic functional dispositions associated with sensitivity to DDA treatment.
Published: 2021
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10. High OX-40 expression in the tumor immune infiltrate is a favorable prognostic factor of overall survival in non-small cell lung cancer

Author: Erminia Massarelli, Vincent K. Lam, Edwin R. Parra, Jaime Rodriguez-Canales, Carmen Behrens, Lixia Diao, Jing Wang, Jorge Blando, Lauren A. Byers, Niranjan Yanamandra, Sara Brett, Peter Morley, Padmanee Sharma, James Allison, Ignacio I. Wistuba, and John V. Heymach
Subjects: OX-40, Lung cancer, NSCLC, Immune checkpoint, immunotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Introduction OX-40 co-stimulatory signaling plays a role in mounting anti-tumor immune responses and clinical trials targeting this pathway are ongoing. However, the association of with OX-40 protein expression with clinical outcomes and pathological features in non-small cell lung cancer (NSCLC) are largely unknown. Methods Surgically-resected stage I-III NSCLC specimens (N = 100) were stained by immunohistochemistry (IHC) for the following immune markers: OX-40, PD-L1, PD-1, CD3, CD4, CD8, CD45RO, CD57, CD68, FOXP3, granzyme B, and ICOS. Immune-related markers mRNA expression were also assessed. We evaluated the association of OX-40 levels with major clinicopathologic variables, including molecular driver mutations. Results OX-40 IHC expression was observed in all tested tumors, predominantly localized in the membrane of the tumor immune infiltrate, and was not associated with a specific clinicopathologic or molecular subtype. High OX-40 expression levels measured by IHC median score were associated with better overall survival (OS) (p = 0.002), independent of CD3/CD8, PD-L1, and ICOS expression. High OX-40 IHC score was associated with increased expression of immune-related genes such as CD3, IFN-gamma, ICOS, CD8, CXCL9, CXCL10, CCL5, granzyme K. Conclusions High OX-40 IHC expression in the tumor immune infiltrate is associated with favorable prognosis and increased levels of immune-related genes including IFN-gamma in patients with surgically resected stage I-III NSCLC. Its prognostic utility is independent of PD-L1 and other common markers of immune activation. High OX-40 expression potentially identifies a unique subgroup of NSCLC that may benefit from co-stimulation with OX-40 agonist antibodies and potentially enhance the efficacy of existing immune checkpoint therapies.
Published: 2019
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11. Oncogenic enhancer of zeste homolog 2 is an actionable target in patients with non‐small cell lung cancer

Author: Bin Shi, Carmen Behrens, Viralkumar Vaghani, Erick Marcelo Riquelme, Jaime Rodriguez‐Canales, Humam Kadara, Heather Lin, Jack Lee, Hui Liu, Ignacio Wistuba, and George Simon
Subjects: biomarkers, enhancer of zeste homolog 2, histone deacetylases, lung cancer, methyl transferase, non‐small cell lung cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background The aims of this study were to investigate the link between enhancer of zeste homolog 2 (EZH2) and histone deacetylase (HDAC) in preclinical studies and in human lung cancer tissue microarrays. Methods Enhancer of zeste homolog 2 and HDAC1 mRNA expression in two lung adenocarcinoma (LUAD) datasets (MDACC and TCGA) were correlated with patient outcomes. We evaluated the association of EZH2 and HDAC1 expression with response to the HDAC1 inhibitor, suberoylanilide hydroxamic acid (SAHA). The response to SAHA was assessed at baseline and after alteration of EZH2 or HDAC mRNA expression in LUAD cell lines. Results Direct correlation was found between EZH2 and HDAC1 expression (P
Published: 2019
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12. Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity

Author: Neus Bota-Rabassedas, Priyam Banerjee, Yichi Niu, Wenjian Cao, Jiayi Luo, Yuanxin Xi, Xiaochao Tan, Kuanwei Sheng, Young-Ho Ahn, Sieun Lee, Edwin Roger Parra, Jaime Rodriguez-Canales, Jacob Albritton, Michael Weiger, Xin Liu, Hou-Fu Guo, Jiang Yu, B. Leticia Rodriguez, Joshua J.A. Firestone, Barbara Mino, Chad J. Creighton, Luisa M. Solis, Pamela Villalobos, Maria Gabriela Raso, Daniel W. Sazer, Don L. Gibbons, William K. Russell, Gregory D. Longmore, Ignacio I. Wistuba, Jing Wang, Harold A. Chapman, Jordan S. Miller, Chenghang Zong, and Jonathan M. Kurie
Subjects: cancer-associated fibroblast, EMT, metastasis, lung cancer, tumor microenvironment, microRNA, Biology (General), QH301-705.5
Abstract: Summary: Cancer cells function as primary architects of the tumor microenvironment. However, the molecular features of cancer cells that govern stromal cell phenotypes remain unclear. Here, we show that cancer-associated fibroblast (CAF) heterogeneity is driven by lung adenocarcinoma (LUAD) cells at either end of the epithelial-to-mesenchymal transition (EMT) spectrum. LUAD cells that have high expression of the EMT-activating transcription factor ZEB1 reprogram CAFs through a ZEB1-dependent secretory program and direct CAFs to the tips of invasive projections through a ZEB1-driven CAF repulsion process. The EMT, in turn, sensitizes LUAD cells to pro-metastatic signals from CAFs. Thus, CAFs respond to contextual cues from LUAD cells to promote metastasis.
Published: 2021
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13. The Society for Immunotherapy of Cancer statement on best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) staining and validation

Author: Ignacio I Wistuba, Michael T Tetzlaff, Carlo B Bifulco, Katharina von Loga, Sacha Gnjatic, Scott J Rodig, Janis M Taube, Keith E Steele, Marlon C Rebelatto, David L Rimm, Ana Lako, Edwin R Parra, Guray Akturk, Michael Angelo, Elizabeth L Engle, Shirley Greenbaum, Noah F Greenwald, Cyrus V Hedvat, Travis J Hollmann, Jonathan Juco, Jaime Rodriguez-Canales, Kurt A Schalper, Edward C Stack, Cláudia S Ferreira, Konstanty Korski, Emanuel Schenck, and Michael J Surace
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Objectives The interaction between the immune system and tumor cells is an important feature for the prognosis and treatment of cancer. Multiplex immunohistochemistry (mIHC) and multiplex immunofluorescence (mIF) analyses are emerging technologies that can be used to help quantify immune cell subsets, their functional state, and their spatial arrangement within the tumor microenvironment.Methods The Society for Immunotherapy of Cancer (SITC) convened a task force of pathologists and laboratory leaders from academic centers as well as experts from pharmaceutical and diagnostic companies to develop best practice guidelines for the optimization and validation of mIHC/mIF assays across platforms.Results Representative outputs and the advantages and disadvantages of mIHC/mIF approaches, such as multiplexed chromogenic IHC, multiplexed immunohistochemical consecutive staining on single slide, mIF (including multispectral approaches), tissue-based mass spectrometry, and digital spatial profiling are discussed.Conclusions mIHC/mIF technologies are becoming standard tools for biomarker studies and are likely to enter routine clinical practice in the near future. Careful assay optimization and validation will help ensure outputs are robust and comparable across laboratories as well as potentially across mIHC/mIF platforms. Quantitative image analysis of mIHC/mIF output and data management considerations will be addressed in a complementary manuscript from this task force.
Published: 2020
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14. Validation of multiplex immunofluorescence panels using multispectral microscopy for immune-profiling of formalin-fixed and paraffin-embedded human tumor tissues

Author: Edwin R. Parra, Naohiro Uraoka, Mei Jiang, Pamela Cook, Don Gibbons, Marie-Andrée Forget, Chantale Bernatchez, Cara Haymaker, Ignacio I. Wistuba, and Jaime Rodriguez-Canales
Subjects: Medicine, Science
Abstract: Abstract Immune-profiling is becoming an important tool to identify predictive markers for the response to immunotherapy. Our goal was to validate multiplex immunofluorescence (mIF) panels to apply to formalin-fixed and paraffin-embedded tissues using a set of immune marker antibodies, with the Opal™ 7 color Kit (PerkinElmer) in the same tissue section. We validated and we described two panels aiming to characterize the expression of PD-L1, PD-1, and subsets of tumor associated immune cells. Panel 1 included pancytokeratin (AE1/AE3), PD-L1, CD4, CD8, CD3, CD68, and DAPI, and Panel 2 included pancytokeratin, PD-1, CD45RO, granzyme B, CD57, FOXP3, and DAPI. After all primary antibodies were tested in positive and negative controls by immunohistochemistry and uniplex IF, panels were developed and simultaneous marker expressions were quantified using the Vectra 3.0™ multispectral microscopy and image analysis InForm™ 2.2.1 software (PerkinElmer).These two mIF panels demonstrated specific co-localization in different cells that can identify the expression of PD-L1 in malignant cells and macrophages, and different T-cell subpopulations. This mIF methodology can be an invaluable tool for tumor tissue immune-profiling to allow multiple targets in the same tissue section and we provide that is accurate and reproducible method when is performed carefully under pathologist supervision.
Published: 2017
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15. Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis

Author: Mark J. Schliekelman, Chad J. Creighton, Brandi N. Baird, Yulong Chen, Priyam Banerjee, Neus Bota-Rabassedas, Young-Ho Ahn, Jonathon D. Roybal, Fengju Chen, Yiqun Zhang, Dhruva K. Mishra, Min P. Kim, Xin Liu, Barbara Mino, Pamela Villalobos, Jaime Rodriguez-Canales, Carmen Behrens, Ignacio I. Wistuba, Samir M. Hanash, and Jonathan M. Kurie
Subjects: Medicine, Science
Abstract: Abstract Cancer-associated fibroblasts (CAFs) regulate diverse intratumoral biological programs and can promote or inhibit tumorigenesis, but those CAF populations that negatively impact the clinical outcome of lung cancer patients have not been fully elucidated. Because Thy-1 (CD90) marks CAFs that promote tumor cell invasion in a murine model of KrasG12D–driven lung adenocarcinoma (KrasLA1), here we postulated that human lung adenocarcinomas containing Thy-1+ CAFs have a worse prognosis. We first examined the location of Thy-1+ CAFs within human lung adenocarcinomas. Cells that co-express Thy-1 and α-smooth muscle actin (αSMA), a CAF marker, were located on the tumor periphery surrounding collectively invading tumor cells and in perivascular regions. To interrogate a human lung cancer database for the presence of Thy-1+ CAFs, we isolated Thy-1+ CAFs and normal lung fibroblasts (LFs) from the lungs of KrasLA1 mice and wild-type littermates, respectively, and performed global proteomic analysis on the murine CAFs and LFs, which identified 425 proteins that were differentially expressed. Used as a probe to identify Thy-1+ CAF-enriched tumors in a compendium of 1,586 lung adenocarcinomas, the presence of the 425-gene signature predicted a significantly shorter survival. Thus, Thy-1 marks a CAF population that adversely impacts clinical outcome in human lung cancer.
Published: 2017
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16. Taxane-Platin-Resistant Lung Cancers Co-develop Hypersensitivity to JumonjiC Demethylase Inhibitors

Author: Maithili P. Dalvi, Lei Wang, Rui Zhong, Rahul K. Kollipara, Hyunsil Park, Juan Bayo, Paul Yenerall, Yunyun Zhou, Brenda C. Timmons, Jaime Rodriguez-Canales, Carmen Behrens, Barbara Mino, Pamela Villalobos, Edwin R. Parra, Milind Suraokar, Apar Pataer, Stephen G. Swisher, Neda Kalhor, Natarajan V. Bhanu, Benjamin A. Garcia, John V. Heymach, Kevin Coombes, Yang Xie, Luc Girard, Adi F. Gazdar, Ralf Kittler, Ignacio I. Wistuba, John D. Minna, and Elisabeth D. Martinez
Subjects: Jumonji demethylases, JIB-04, GSK-J4, drug resistance, taxane-platin chemotherapy, KDM, demethylase inhibitors, histone methylation, histone demethylases, lung cancer, Biology (General), QH301-705.5
Abstract: Although non-small cell lung cancer (NSCLC) patients benefit from standard taxane-platin chemotherapy, many relapse, developing drug resistance. We established preclinical taxane-platin-chemoresistance models and identified a 35-gene resistance signature, which was associated with poor recurrence-free survival in neoadjuvant-treated NSCLC patients and included upregulation of the JumonjiC lysine demethylase KDM3B. In fact, multi-drug-resistant cells progressively increased the expression of many JumonjiC demethylases, had altered histone methylation, and, importantly, showed hypersensitivity to JumonjiC inhibitors in vitro and in vivo. Increasing taxane-platin resistance in progressive cell line series was accompanied by progressive sensitization to JIB-04 and GSK-J4. These JumonjiC inhibitors partly reversed deregulated transcriptional programs, prevented the emergence of drug-tolerant colonies from chemo-naive cells, and synergized with standard chemotherapy in vitro and in vivo. Our findings reveal JumonjiC inhibitors as promising therapies for targeting taxane-platin-chemoresistant NSCLCs.
Published: 2017
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17. Targeting CDK9 and MCL-1 by a new CDK9/p-TEFb inhibitor with and without 5-fluorouracil in esophageal adenocarcinoma

Author: Zhimin Tong, Alicia Mejia, Omkara Veeranki, Anuj Verma, Arlene M. Correa, Rashmi Dokey, Viren Patel, Luisa Maren Solis, Barbara Mino, Riham Kathkuda, Jaime Rodriguez-Canales, Steven H. Lin, Sunil Krishnan, Scott Kopetz, Mariela Blum, Jaffer A. Ajani, Wayne L. Hofstetter, and Dipen M. Maru
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background: CDK9 inhibitors are antitumorigenic against solid tumors, including esophageal adenocarcinoma (EAC). However, efficacy of a CDK9 inhibitor combined with 5-fluorouracil (5-FU) and target proteins that are targeted by these agents in EAC are unknown. Methods: The anti-EAC efficacy of a new CDK9 inhibitor, BAY1143572, with and without 5-FU was assessed in vitro and in xenograft models in athymic nu/nu mice. Synergy between BAY1143572 and 5-FU in inhibiting cell proliferation was analyzed by calculating the combination index using CompuSyn software. Potential targets of BAY1143572 and 5-FU were identified by reverse-phase protein array. The effects of BAY1143572 and 5-FU on MCL-1 in vitro were analyzed by Western blotting, quantitative real-time polymerase chain reaction, and chromatin immunoprecipitation assay. MCL-1 protein expression in tumors from patients with locoregional EAC treated with chemoradiation and surgery was assessed by immunohistochemistry. Results: BAY1143572 had dose-dependent antiproliferative and proapoptotic effects and demonstrated synergy with 5-FU against EAC in vitro . The median volumes of FLO-1 and ESO-26 xenografts treated with 5-FU plus BAY114352 were significantly smaller than those of xenografts treated with either agent alone ( p
Published: 2019
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18. Cultural Heritage Restoration of a Hemispherical Vault by 3D Modelling and Projection of Video Images with Unknown Parameters and from Unknown Locations

Author: Jose Herraez, Jose L. Denia, Enrique Priego, Pablo Navarro, Maria T. Martin, and Jaime Rodriguez
Subjects: reverse engineering, cultural heritage, photogrammetry, 3D model, laser scanner, video mapping, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract: Reverse engineering applied to architectural restoration for the reconstruction of structural surfaces depends on metric precision. Sometimes there are elements on these surfaces whose value is even higher than the building itself. This is the case for many churches whose ceilings have pictorial works of art. Reconstruction requires the existence of some identifiable remainder and/or a surface geometry that enables mathematical development. In our case, the vault has an irregular hemispherical geometry (without possible mathematical development), and there are no significant remains of the painting (which was destroyed by a fire). Through the 3D modelling of the irregular vault and two historic frames with a camera of unknown geometry, an inverse methodology is designed to project the original painting without metric deformations. For this, a new methodology to locate the camera positions is developed. After, a 3D virtual mathematical model of the complete image on the vault is calculated, and from it, partial 3D virtual images are automatically calculated depending on the variable unknown positions of the video cannons (distributed along the upper corridor of the apse) that will project them (visually forming a perfect complete 3D image).
Published: 2021
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19. Fatty Acid Oxidation Mediated by Acyl-CoA Synthetase Long Chain 3 Is Required for Mutant KRAS Lung Tumorigenesis

Author: Mahesh S. Padanad, Georgia Konstantinidou, Niranjan Venkateswaran, Margherita Melegari, Smita Rindhe, Matthew Mitsche, Chendong Yang, Kimberly Batten, Kenneth E. Huffman, Jingwen Liu, Ximing Tang, Jaime Rodriguez-Canales, Neda Kalhor, Jerry W. Shay, John D. Minna, Jeffrey McDonald, Ignacio I. Wistuba, Ralph J. DeBerardinis, and Pier Paolo Scaglioni
Subjects: ACSL3, mutant KRAS, lung cancer, cancer metabolism, fatty acid oxidation, lipid metabolism, mouse cancer models, Biology (General), QH301-705.5
Abstract: KRAS is one of the most commonly mutated oncogenes in human cancer. Mutant KRAS aberrantly regulates metabolic networks. However, the contribution of cellular metabolism to mutant KRAS tumorigenesis is not completely understood. We report that mutant KRAS regulates intracellular fatty acid metabolism through Acyl-coenzyme A (CoA) synthetase long-chain family member 3 (ACSL3), which converts fatty acids into fatty Acyl-CoA esters, the substrates for lipid synthesis and β-oxidation. ACSL3 suppression is associated with depletion of cellular ATP and causes the death of lung cancer cells. Furthermore, mutant KRAS promotes the cellular uptake, retention, accumulation, and β-oxidation of fatty acids in lung cancer cells in an ACSL3-dependent manner. Finally, ACSL3 is essential for mutant KRAS lung cancer tumorigenesis in vivo and is highly expressed in human lung cancer. Our data demonstrate that mutant KRAS reprograms lipid homeostasis, establishing a metabolic requirement that could be exploited for therapeutic gain.
Published: 2016
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20. PIAS1-FAK Interaction Promotes the Survival and Progression of Non-Small Cell Lung Cancer

Author: Jerfiz D. Constanzo, Ke-jing Tang, Smita Rindhe, Margherita Melegari, Hui Liu, Ximing Tang, Jaime Rodriguez-Canales, Ignacio Wistuba, and Pier Paolo Scaglioni
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: The sequence of genomic alterations acquired by cancer cells during tumor progression and metastasis is poorly understood. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that integrates cytoskeleton remodeling, mitogenic signaling and cell survival. FAK has previously been reported to undergo nuclear localization during cell migration, cell differentiation and apoptosis. However, the mechanism behind FAK nuclear accumulation and its contribution to tumor progression has remained elusive. We report that amplification of FAK and the SUMO E3 ligase PIAS1 gene loci frequently co-occur in non-small cell lung cancer (NSCLC) cells, and that both gene products are enriched in a subset of primary NSCLCs. We demonstrate that endogenous FAK and PIAS1 proteins interact in the cytoplasm and the cell nucleus of NSCLC cells. Ectopic expression of PIAS1 promotes proteolytic cleavage of the FAK C-terminus, focal adhesion maturation and FAK nuclear localization. Silencing of PIAS1 deregulates focal adhesion turnover, increases susceptibility to apoptosis in vitro and impairs tumor xenograft formation in vivo. Nuclear FAK in turn stimulates gene transcription favoring DNA repair, cell metabolism and cytoskeleton regulation. Consistently, ablation of FAK by CRISPR/Cas9 editing, results in basal DNA damage, susceptibility to ionizing radiation and impaired oxidative phosphorylation. Our findings provide insight into a mechanism regulating FAK cytoplasm-nuclear distribution and demonstrate that FAK activity in the nucleus promotes NSCLC survival and progression by increasing cell-ECM interaction and DNA repair regulation.
Published: 2016
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21. A Functional Spatial Analysis Platform for Discovery of Immunological Interactions Predictive of Low-Grade to High-Grade Transition of Pancreatic Intraductal Papillary Mucinous Neoplasms

Author: Souptik Barua, Luisa Solis, Edwin Roger Parra, Naohiro Uraoka, Mei Jiang, Huamin Wang, Jaime Rodriguez-Canales, Ignacio Wistuba, Anirban Maitra, Subrata Sen, and Arvind Rao
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Intraductal papillary mucinous neoplasms (IPMNs), critical precursors of the devastating tumor pancreatic ductal adenocarcinoma (PDAC), are poorly understood in the pancreatic cancer community. Researchers have shown that IPMN patients with high-grade dysplasia have a greater risk of subsequent development of PDAC in the remnant pancreas than do patients with low-grade dysplasia. In this study, we built a computational prediction model that encapsulates the spatial cellular interactions in IPMNs that play key roles in the transformation of low-grade IPMN cysts to high-grade cysts en route to PDAC. Using multiplex immunofluorescent images of IPMN cysts, we adopted algorithms from spatial statistics and functional data analysis to create metrics that summarize the spatial interactions in IPMNs. We showed that an ensemble of models learned using these spatial metrics can robustly predict, with high accuracy, (1) the dysplasia grade (low vs high grade) and (2) the risk of a low-grade cyst progressing to a high-grade cyst. We obtained high classification accuracies on both tasks, with areas under the curve of 0.81 (95% confidence interval: 0.71-0.9) for task 1 and 0.81 (95% confidence interval: 0.7-0.94) for task 2. To the best of our knowledge, this is the first application of an ensemble machine learning approach for discovering critical cellular spatial interactions in IPMNs using imaging data . We envision that our work can be used as a risk assessment tool for patients diagnosed with IPMNs and facilitate greater understanding and investigation of the cellular interactions that cause transition of IPMNs to PDAC.
Published: 2018
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22. Colloidal Stability and Magnetic Field-Induced Ordering of Magnetorheological Fluids Studied with a Quartz Crystal Microbalance

Author: Jaime Rodriguez-López, Pedro Castro, Juan de Vicente, Diethelm Johannsmann, Luis Elvira, Jose R. Morillas, and Francisco Montero de Espinosa
Subjects: TSM resonator, magnetorheological fluid, QCM, positive resonant frequency shift, micron-sized magnetic particles, sedimentation, magnetic field intensity, Chemical technology, TP1-1185
Abstract: This work proposes the use of quartz crystal microbalances (QCMs) as a method to analyze and characterize magnetorheological (MR) fluids. QCM devices are sensitive to changes in mass, surface interactions, and viscoelastic properties of the medium contacting its surface. These features make the QCM suitable to study MR fluids and their response to variable environmental conditions. MR fluids change their structure and viscoelastic properties under the action of an external magnetic field, this change being determined by the particle volume fraction, the magnetic field strength, and the presence of thixotropic agents among other factors. In this work, the measurement of the resonance parameters (resonance frequency and dissipation factor) of a QCM are used to analyze the behavior of MR fluids in static conditions (that is, in the absence of external mechanical stresses). The influence of sedimentation under gravity and the application of magnetic fields on the shifts of resonance frequency and dissipation factor were measured and discussed in the frame of the coupled resonance produced by particles touching the QCM surface. Furthermore, the MR-fluid/QCM system has a great potential for the study of high-frequency contact mechanics because the translational and rotational stiffness of the link between the surface and the particles can be tuned by the magnetic field.
Published: 2015
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23. Integration of Architectural and Cytologic Driven Image Algorithms for Prostate Adenocarcinoma Identification

Author: Jason Hipp, James Monaco, L. Priya Kunju, Jerome Cheng, Yukako Yagi, Jaime Rodriguez-Canales, Michael R. Emmert-Buck, Stephen Hewitt, Michael D. Feldman, John E. Tomaszewski, Mehmet Toner, Ronald G. Tompkins, Thomas Flotte, David Lucas, John R. Gilbertson, Anant Madabhushi, and Ulysses Balis
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract: Introduction: The advent of digital slides offers new opportunities within the practice of pathology such as the use of image analysis techniques to facilitate computer aided diagnosis (CAD) solutions. Use of CAD holds promise to enable new levels of decision support and allow for additional layers of quality assurance and consistency in rendered diagnoses. However, the development and testing of prostate cancer CAD solutions requires a ground truth map of the cancer to enable the generation of receiver operator characteristic (ROC) curves. This requires a pathologist to annotate, or paint, each of the malignant glands in prostate cancer with an image editor software - a time consuming and exhaustive process.
Published: 2012
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24. Discrecionalidad y motivación del acto administrativo en la ley española de procedimiento administrativo

Author: Jaime Rodriguez-Arana Muñoz
Subjects: Discrecionalidad, Procedimiento administrativo, Conceptos, Law
Abstract: El artículo nos presenta una aproximación doctrinal al concepto de discrecionalidad y nos describe sus presupuestos técnicos. Seguidamente, el artículo hace hincapié en que resulta necesario que se incorpore, en todos los actos administrativos, alguna referencia racional que permita colegir con facilidad los argumentos lógicos de los que trae causa dicha resolución administrativa. Se constituye así, en la otra cara de la moneda, la motivación de la discrecionalidad, pues de lo contrario estaríamos entrando en el mundo de la arbitrariedad.
Published: 2011

25. BIOMETRICS IN NETWORKING: BALANCING IMPLEMENTATION WITH THE RIGHT TO PRIVACY

Author: Kevin Elder and Jaime Rodriguez
Subjects: Information technology, T58.5-58.64, Electronic computers. Computer science, QA75.5-76.95
Abstract: To investigate information systems project success, this study uses a web-based survey to collect data from 428 project managers and 65 other team participants. The data are analyzed for reliability and validity, and structural equation modeling is used to test hypotheses related to project success. Results show that monitoring predicts privately held information which in turn predicts project success, and that monitoring also directly predicts project success. The testing finds no analogous relationships between project success and outcome-basis or goal conflict. The study contributes by showing that contract type (i.e., more versus less outcome-based), monitoring, goal conflict, and privately held information are multi-dimensional constructs and provides instruments for their measurement. Perhaps surprisingly, it suggests that the monitoring of systems developers may be a more effective way to improve project outcome than promising to reward them for that outcome.
Published: 2011

26. Videojuegos como simulaciones inmersivas. El caso'Atrapados', Narrativa transmedia e investigación de la inteligencia colectiva

Author: Carlos Roberto Torres, Jaime Rodriguez, and Luis Gonzalez
Subjects: videojuegos, simulación, inmersión, Education (General), L7-991
Abstract: Este texto profundiza el concepto simulación cuestionando algunas de sus caracterizaciones más difundidas y argumenta por qué, contrariamente a estas apreciaciones, todos los videojuegos son simulaciones. Posteriormente, con el objetivo de precisar cuál es la particularidad que diferencia al videojuego de otras formas de simulación, se propone la categoría de Inmersión como uno de los rasgos particulares de este medio. Para explicar esta idea se revisa críticamente el trabajo de algunos de los autores más destacados que han profundizado en este concepto, contrastándolo con diferentes definiciones canónicas del juego a lo largo del siglo XX y con reflexiones más recientes provenientes del estudio del videojuego. A partir de este recorrido se revisa el caso del videojuego “Atrapados” (Jaime Alejandro Rodríguez, 2014), usando los conceptos de simulación e inmersión para explicar su funcionamiento.
Published: 2015

27. Computer-aided laser dissection: A microdissection workflow leveraging image analysis tools

Author: Jason D Hipp, Donald J Johann, Yun Chen, Anant Madabhushi, James Monaco, Jerome Cheng, Jaime Rodriguez-Canales, Martin C Stumpe, Greg Riedlinger, Avi Z Rosenberg, Jeffrey C Hanson, Lakshmi P Kunju, Michael R Emmert-Buck, Ulysses J Balis, and Michael A Tangrea
Subjects: Image analysis, microdissection, probabilistic pairwise Markov model, SIVQ, Computer applications to medicine. Medical informatics, R858-859.7, Pathology, RB1-214
Abstract: Introduction: The development and application of new molecular diagnostic assays based on next-generation sequencing and proteomics require improved methodologies for procurement of target cells from histological sections. Laser microdissection can successfully isolate distinct cells from tissue specimens based on visual selection for many research and clinical applications. However, this can be a daunting task when a large number of cells are required for molecular analysis or when a sizeable number of specimens need to be evaluated. Materials and Methods: To improve the efficiency of the cellular identification process, we describe a microdissection workflow that leverages recently developed and open source image analysis algorithms referred to as computer-aided laser dissection (CALD). CALD permits a computer algorithm to identify the cells of interest and drive the dissection process. Results: We describe several “use cases” that demonstrate the integration of image analytic tools probabilistic pairwise Markov model, ImageJ, spatially invariant vector quantization (SIVQ), and eSeg onto the ThermoFisher Scientific ArcturusXT and Leica LMD7000 microdissection platforms. Conclusions: The CALD methodology demonstrates the integration of image analysis tools with the microdissection workflow and shows the potential impact to clinical and life science applications.
Published: 2018
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28. Construção e otimização de um sistema para produção e aplicação de ozônio em escala de laboratório

Author: Airton Kunz, Renato S. Freire, Jarbas J. R. Rohwedder, Nelson Duran, Hector Mansilla, and Jaime Rodriguez
Subjects: Chemistry, QD1-999
Published: 1999

29. Analysis of transcription factor mRNAs in identified oxytocin and vasopressin magnocellular neurons isolated by laser capture microdissection.

Author: Madison Humerick, Jeffrey Hanson, Jaime Rodriguez-Canales, Daniel Lubelski, Omar M Rashid, Yasmmyn D Salinas, Yijun Shi, Todd Ponzio, Raymond Fields, Michael R Emmert-Buck, and Harold Gainer
Subjects: Medicine, Science
Abstract: The oxytocin (Oxt) and vasopressin (Avp) magnocellular neurons (MCNs) in the hypothalamus are the only neuronal phenotypes that are present in the supraoptic nucleus (SON), and are characterized by their robust and selective expression of either the Oxt or Avp genes. In this paper, we take advantage of the differential expression of these neuropeptide genes to identify and isolate these two individual phenotypes from the rat SON by laser capture microdissection (LCM), and to analyze the differential expression of several of their transcription factor mRNAs by qRT-PCR. We identify these neuronal phenotypes by stereotaxically injecting recombinant Adeno-Associated Viral (rAAV) vectors which contain cell-type specific Oxt or Avp promoters that drive expression of EGFP selectively in either the Oxt or Avp MCNs into the SON. The fluorescent MCNs are then dissected by LCM using a novel Cap Road Map protocol described in this paper, and the purified MCNs are extracted for their RNAs. qRT-PCR of these RNAs show that some transcription factors (RORA and c-jun) are differentially expressed in the Oxt and Avp MCNs.
Published: 2013
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30. Corrigendum to 'PIAS1-FAK Interaction Promotes the Survival and Progression of Non–Small Cell Lung Cancer' [Neoplasia 18 (2016) 282-293].

Author: Jerfiz D. Constanzo, Ke-jing Tang, Smita Rindhe, Margherita Melegari, Hui Liu, Ximing Tang, Jaime Rodriguez-Canales, Ignacio Wistuba, and Pier Paolo Scaglioni
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2016
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31. Methylation profiling of mediastinal gray zone lymphoma reveals a distinctive signature with elements shared by classical Hodgkin’s lymphoma and primary mediastinal large B-cell lymphoma

Author: Franziska C. Eberle, Jaime Rodriguez-Canales, Lai Wei, Jeffrey C. Hanson, J. Keith Killian, Hong-Wei Sun, Lisa G. Adams, Stephen M. Hewitt, Wyndham H. Wilson, Stefania Pittaluga, Paul S. Meltzer, Louis M. Staudt, Michael R. Emmert-Buck, and Elaine S. Jaffe
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background Mediastinal gray zone lymphoma is a newly recognized entity with transitional morphological and immunophenotypic features between the nodular sclerosis subtype of Hodgkin’s lymphoma and primary mediastinal large B-cell lymphoma. Diagnostic criteria for mediastinal gray zone lymphoma are still challenging, and the optimal therapy is as yet undetermined. Epigenetic changes have been implicated in the loss of the B-cell program in classical Hodgkin’s lymphoma, and might provide a basis for the immunophenotypic alterations seen in mediastinal gray zone lymphoma.Design and Methods We performed a large-scale DNA methylation analysis of microdissected tumor cells to investigate the biological underpinnings of mediastinal gray zone lymphoma and its association with the related entities classical Hodgkin’s lymphoma and primary mediastinal large B-cell lymphoma, making comparisons with the presumptively less related diffuse large B-cell lymphoma.Results Principal component analysis demonstrated that mediastinal gray zone lymphoma has a distinct epigenetic profile intermediate between classical Hodgkin’s lymphoma and primary mediastinal large B-cell lymphoma but remarkably different from that of diffuse large B-cell lymphoma. Analysis of common hypo- and hypermethylated CpG targets in mediastinal gray zone lymphoma, classical Hodgkin’s lymphoma, primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma was performed and confirmed the findings of the principal component analysis. Based on the epigenetic profiles we were able to establish class prediction models utilizing genes such as HOXA5, MMP9, EPHA7 and DAPK1 which could distinguish between mediastinal gray zone lymphoma, classical Hodgkin’s lymphoma and primary mediastinal large B-cell lymphoma with a final combined prediction of 100%.Conclusions Our data confirm a close relationship between mediastinal gray zone lymphoma and both classical Hodgkin’s lymphoma and primary mediastinal large B-cell lymphoma. However, important differences were observed as well, allowing a clear distinction from both parent entities. Thus, mediastinal gray zone lymphoma cannot be assigned to either classical Hodgkin’s lymphoma or primary mediastinal large B-cell lymphoma, validating the decision to create an intermediate category in the World Health Organization classification.
Published: 2011
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32. El papel central de los usuarios en el derecho energético

Author: Jaime Rodriguez-Arana
Subjects: Derecho administrativo, Law in general. Comparative and uniform law. Jurisprudence, K1-7720
Published: 2007

33. Computer aided diagnostic tools aim to empower rather than replace pathologists: Lessons learned from computational chess

Author: Jason Hipp, Thomas Flotte, James Monaco, Jerome Cheng, Anant Madabhushi, Yukako Yagi, Jaime Rodriguez-Canales, Michael Emmert-Buck, Michael C Dugan, Stephen Hewitt, Mehmet Toner, Ronald G Tompkins, David Lucas, John R Gilbertson, and Ulysses J Balis
Subjects: Computer applications to medicine. Medical informatics, R858-859.7, Pathology, RB1-214
Published: 2011
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34. SIVQ-aided laser capture microdissection: A tool for high-throughput expression profiling

Author: Jason Hipp, Jerome Cheng, Jeffrey C Hanson, Wusheng Yan, Phil Taylor, Nan Hu, Jaime Rodriguez-Canales, Jennifer Hipp, Michael A Tangrea, Michael R Emmert-Buck, and Ulysses Balis
Subjects: Laser capture microdissection, microarray, Spatially Invariant Vector Quantization, Computer applications to medicine. Medical informatics, R858-859.7, Pathology, RB1-214
Abstract: Introduction: Laser capture microdissection (LCM) facilitates procurement of defined cell populations for study in the context of histopathology. The morphologic assessment step in the LCM procedure is time consuming and tedious, thus restricting the utility of the technology for large applications. Results: Here, we describe the use of Spatially Invariant Vector Quantization (SIVQ) for histological analysis and LCM. Using SIVQ, we selected vectors as morphologic predicates that were representative of normal epithelial or cancer cells and then searched for phenotypically similar cells across entire tissue sections. The selected cells were subsequently auto-microdissected and the recovered RNA was analyzed by expression microarray. Gene expression profiles from SIVQ-LCM and standard LCM-derived samples demonstrated highly congruous signatures, confirming the equivalence of the differing microdissection methods. Conclusion: SIVQ-LCM improves the work-flow of microdissection in two significant ways. First, the process is transformative in that it shifts the pathologist′s role from technical execution of the entire microdissection to a limited-contact supervisory role, enabling large-scale extraction of tissue by expediting subsequent semi-autonomous identification of target cell populations. Second, this work-flow model provides an opportunity to systematically identify highly constrained cell populations and morphologically consistent regions within tissue sections. Integrating SIVQ with LCM in a single environment provides advanced capabilities for efficient and high-throughput histological-based molecular studies.
Published: 2011
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35. Image microarrays (IMA): Digital pathology′s missing tool

Author: Jason Hipp, Jerome Cheng, Liron Pantanowitz, Stephen Hewitt, Yukako Yagi, James Monaco, Anant Madabhushi, Jaime Rodriguez-canales, Jeffrey Hanson, Sinchita Roy-Chowdhuri, Armando C Filie, Michael D Feldman, John E Tomaszewski, Natalie NC Shih, Victor Brodsky, Giuseppe Giaccone, Michael R Emmert-Buck, and Ulysses J Balis
Subjects: IMA, SIVQ, TMA, WSI, Computer applications to medicine. Medical informatics, R858-859.7, Pathology, RB1-214
Abstract: Introduction: The increasing availability of whole slide imaging (WSI) data sets (digital slides) from glass slides offers new opportunities for the development of computer-aided diagnostic (CAD) algorithms. With the all-digital pathology workflow that these data sets will enable in the near future, literally millions of digital slides will be generated and stored. Consequently, the field in general and pathologists, specifically, will need tools to help extract actionable information from this new and vast collective repository. Methods: To address this limitation, we designed and implemented a tool (dCORE) to enable the systematic capture of image tiles with constrained size and resolution that contain desired histopathologic features. Results: In this communication, we describe a user-friendly tool that will enable pathologists to mine digital slides archives to create image microarrays (IMAs). IMAs are to digital slides as tissue microarrays (TMAs) are to cell blocks. Thus, a single digital slide could be transformed into an array of hundreds to thousands of high quality digital images, with each containing key diagnostic morphologies and appropriate controls. Current manual digital image cut-and-paste methods that allow for the creation of a grid of images (such as an IMA) of matching resolutions are tedious. Conclusion: The ability to create IMAs representing hundreds to thousands of vetted morphologic features has numerous applications in education, proficiency testing, consensus case review, and research. Lastly, in a manner analogous to the way conventional TMA technology has significantly accelerated in situ studies of tissue specimens use of IMAs has similar potential to significantly accelerate CAD algorithm development.
Published: 2011
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36. Elective surgery system strengthening: development, measurement, and validation of the surgical preparedness index across 1632 hospitals in 119 countries

Author: Glasbey, James C, Abbott, Tom EF, Ademuyiwa, Adesoji, Adisa, Adewale, AlAmeer, Ehab, Alshryda, Sattar, Arnaud, Alexis P, Bankhead-Kendall, Brittany, Abou Chaar, M K, Chaudhry, Daoud, Costas-Chavarri, Ainhoa, Cunha, Miguel F, Davies, Justine I, Desai, Anant, Elhadi, Muhammed, Fiore, Marco, Fitzgerald, James Edward, Fourtounas, Maria, Fowler, Alex James, Futaba, Kay, Gallo, Gaetano, Ghosh, Dhruva, Gujjuri, Rohan R, Hamilton, Rebecca, Haque, Parvez, Harrison, Ewen M, Hutchinson, Peter, Hyman, Gabriella, Isik, Arda, Jayarajah, Umesh, Kaafarani, Haytham MA, Kadir, Bryar, Lawani, Ismail, Lederhuber, Hans, Li, Elizabeth, Löffler, Markus W, Lorena, Maria Aguilera, Mann, Harvinder, Martin, Janet, Mazingi, Dennis, McClain, Craig D, McLean, Kenneth A, Meara, John G, Ramos-De La Medina, Antonio, Mengesha, Mengistu, Minaya, Ana, Modolo, Maria Marta, Moore, Rachel, Morton, Dion, Nepogodiev, Dmitri, Ntirenganya, Faustin, Pata, Francesco, Pearse, Rupert, Picciochi, Maria, Pinkney, Thomas, Pockney, Peter, van Ramshorst, Gabrielle H, Richards, Toby, Roslani, April Camilla, Satoi, Sohei, Sayyed, Raza, Shaw, Richard, Simões, Joana FF, Smart, Neil, Sullivan, Richard, Sund, Malin, Sundar, Sudha, Tabiri, Stephen, Taylor, Elliott H, Venn, Mary L, Wickramasinghe, Dakshitha, Wright, Naomi, Yip, Sebastian Bernardo Shu, Bhangu, Aneel, Omar, Omar, Harrison, Ewen, Bhangu, Aneel A, Siaw-Acheampong, Kwabena, Benson, Ruth A, Bywater, Edward, Dawson, Brett E, Evans, Jonathan P, Heritage, Emily, Jones, Conor S, Kamarajah, Sivesh K, Khatri, Chetan, Khaw, Rachel A, Keatley, James M, Knight, Andrew, Lawday, Samuel, Mann, Harvinder S, Marson, Ella J, Mckay, Siobhan C, Mills, Emily C, Pellino, Gianluca, Tiwari, Abhinav, Trout, Isobel M, Wilkin, Richard JW, Abukhalaf, Sadi, Adamina, Michel, Ademuyiwa, Adesoji O, Agarwal, Arnav, Akkulak, Murat, Alameer, Ehab, Alderson, Derek, Alakaloko, Felix, Albertsmeier, Markus, Alser, Osaid, Alshaar, Muhammad, Augestad, Knut Magne, Ayasra, Faris, Azevedo, José, Bankhead-Kendall, Brittany K, Barlow, Emma, Beard, David, Blanco-Colino, Ruth, Brar, Amanpreet, Minaya-Bravo, Ana, Breen, Kerry A, Bretherton, Chris, Buarque, Igor Lima, Burke, Joshua, Caruana, Edward J, Chaar, Mohammad, Chakrabortee, Sohini, Christensen, Peter, Cox, Daniel, Cukier, Moises, Davidson, Giana H, Di Saverio, Salomone, Drake, Thomas M, Edwards, John G, Emile, Sameh, Farik, Shebani, Ford, Samuel, Garmanova, Tatiana, Gomes, Gustavo Mendonça Ataíde, Grecinos, Gustavo, Griffiths, Ewen A, Gruendl, Magdalena, Halkias, Constantine, Hisham, Intisar, Hutchinson, Peter J, Hwang, Shelley, Jenkinson, Michael D, Jonker, Pascal, Keller, Debby, Kolias, Angelos, Kruijff, Schelto, Leventoglu, Sezai, Litvin, Andrey, Loehrer, Andrew, Major, Piotr, Mashbari, Hassan N, Metallidis, Symeon, Mohan, Helen M, Moszkowicz, David, Moug, Susan, Ng-Kamstra, Joshua S, Maimbo, Mayaba, Negoi, Ionut, Niquen, Milagros, Olivos, Maricarmen, Oussama, Kacimi, Outani, Oumaima, Parreno-Sacdalanm, Marie Dione, Rivera, Carlos Jose Perez, Pinkney, Thomas D, Plas, Willemijn van der, Qureshi, Ahmad, Radenkovic, Dejan, Revell, Elliot J, Roberts, Keith, Roslani, April C, Rutegård, Martin, Segura-Sampedro, Juan José, Santos, Irène, Schache, Andrew, Schnitzbauer, Andreas A, Seyi-Olajide, Justina O, Sharma, Neil, Shaw, Catherine A, Shu, Sebastian, Soreide, Kjetil, Spinelli, Antonino, Stewart, Grant D, Townend, Philip, Tsoulfas, Georgios, Vidya, Raghavan, Vimalachandran, Dale, Warren, Oliver J, Wedderburn, Duane, EuroSurg, NA, European Society of Coloproctology (ESCP), NA, Global Initiative for Children's Surgery, NA, GlobalSurg, NA, GlobalPaedSurg, NA, ItSURG, NA, PTSurg, NA, SpainSurg, NA, Italian Society of Colorectal Surgery, NA, Association of Surgeons in Training, NA, Irish Surgical Research Collaborative (ISRC), NA, Transatlantic Australasian Retroperitoneal Sarcoma Working, NA, Italian Society of Surgical Oncology, NA, Booth, Lesley, Barker, Margaret, Barker, Neil, Cooke, Shirley, Doré, Suzanne, Horwood, Nigel, Runigamugabo, Emmy, Weir, Carrie Tierney, Bahrami-Hessari, Mike, Riaz, Asad, Shah, Jaffer, Safi, Mohammed, Thereska, Dariel, Dajti, Irida, Cheddadi, Riadh, Tidjane, Anisse, Quinteros, Carlos A, khelfaoui, Ahmed, Salem, Khalifa M, Riffi, Omar, Kacimi, Salah Eddine O, Loudjedi, Salim, Damerdji, Tidjani, Pantoja Pachajoa, Diana A, Palacios Huatuco, René M, Alvarez, Fernando A, Doniquian, Alejandro M, Abeldaño Zuñiga, Roberto A, Schlottmann, Francisco, Cobos, Carlos M, Gigena, Cecilia, Forneris, Agustin Albani, Duro, Agustin, García-Mansilla, Agustín M, Busnelli, Virginia Cano, Poggi, Catalina, Mercado, Pedro L, González, Marcos, Castro Lalin, Agustina F, Mayer, Horacio F, Brandariz, Rodrigo, Slullitel, Pablo A, Boudou, Rocio, Lobos, Pablo A, Uffelmann, María C, Petersen, Maria L, Luzzi, Emilia, Padilla Lichtenberger, Fernando L, Crespi Amor, María S, Zarratea, Celeste S, Esteves, Tomas A, Gemelli, Nicolas A, Tirapegui, Sebastián, Liyo, Juan, Scherñuk, Jordán, Boccalatte, Luis A, Balmaceda, Ruben D, D'Addino, Jose L, Caubet, María M, Calderón Arancibia, José A, Chwat, Carina, Morris, Brian, Avellaneda, Nicolas, Pedraza Salazar, Ivana I, Eskinazi, Diego G, Vargas, Lara, Muriel, María E, Lucchini, Sergio M, Gosselink, Martijn P, Davis, Amelia L, Barker, John C, Qin, Kirby R, Proud, David M, Cox, Daniel RA, Goh, Su Kah, Liu, David S, Wu, Damien M, Merrett, Neil D, Badiani, Sarit S, Sengupta, Shomik, Jain, Anshini, Steen, Christopher J, Wong, Enoch, Ip, Christopher CK, Leaning, Matthew G, McCartney, Conor B, Gananadha, Sivakumar, Yeap, Evie FW, Stevens, Sean G, Vu, Anh N, Martin, Sarah A, Stanley, Guy H M, Watson, David I, Townend, Philip J, Young, Thomas K, Cox, Georgia T, Dawson, Amanda C, Laura, Sharon E, Lun, Elizabeth W Y, Liang, Ina X, O'Neill, Christine J, Lott, Natalie J, Chuan, Alwin, Saravanan, SK, Gundara, Justin, Ong, Bee Shan, Nataraja, Ramesh M, Pacilli, Maurizio, Foley, Daniel M, Ooi, Geraldine J, Traeger, Luke, MacDermid, Ewan, 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Kassab, Mohamad B, Abou-Abbass, Hussein, Awad, Rabih F, El Assaad, Hadi, Serhan, Fatima Ghazi, Karout, Lina, Chowdhary, Anisa, Itani, Rania, Abu Hamrah, Ali A A, Bellah, Almoataz, Algatanesh, Nassib S, Duwebi, Mousab A, Alkouba, Esraa T, Algehani, Hala M, Alsharif, Monther, Al-maadany, Faraj S, Elkhafeefi, Fatimah S, Buimsaedah, Ahmad M, Ghazal, Sarah M, Amnaina, Mohamed G, Yagoub, Ghozlan Y, yahia, Hana Ramadan bin, Bareig, Elham Hussin, BenHamida, Bahaeddin, Alkimeeshi, Nayrouz, Marwan, Malak, Muhammed, Nawal Aldokali, Benamer, Eman M, Othman, Rema H, Momen, Ahmed A, Ayad, Kusay A, Aldokali, Nawal, Mohammed, Alsnosy Abdullah Khalefa, Sanousi, Enas F, Aboubakr, Saed J, Aboubakr, Islam F, Alttaira, Amal, Benatiga, Sara A, Alteerah, Ilham A, Aldressi, Wafa, Elhwety, Marwa O, Kalifa, Mohamed Fathi, Glessa, Maram A, Abubaker, Taha, Shembesh, Hassan A, Alansari, Arowa, Alkaseek, Akram M, Abusannuga, Malek Mohamed, Alawami, Mohammed A, Elhajdawe, Fras Ammar, Benamwor, Aihab Salem, Aween, Husayn M, Kriem, Eslam, Al Islam Benjouira, Rayet, Shagour, Sana Moussa, Ali, Hajar Alamin, Awrayit, Ahmed I, Matoug, Salmin Ibrahim, Abdesalam, Rema Ibrahim, Ouakouak, Ikhlas M, Aldarraji, Ali H, Elmahdi, Ameerah Faraj, Mohamed, Zinelabedin, Khan, Samera M, Gerwash, Ahmed A, Aboubeirah, Mohammed Khayri, Drera, Nosaiba Jalal, Sinan, Marwa A, Abujrad, Ekram Abdulhamid, Biala, Marwa, Gidiem, Doaa A, Aljamal, Sarah A, Hamuda, Esmail M, Manhus, Hussamuddin Abusaa, Binnawara, Muhannud Hassan, Msherghi, Ahmed A, Ajala, Mohamed, Shetty, Nadia D, Kanna, Sanad S, Said, Mohamed H, Elghazal, Mohamed M, Alwarfalli, Moaz Mustafa, Alharari, Mohamed A, Etayeb, Eslam, Abozid, Anwaar M, Rdadi, Kariman, Alferis, Tariq, Ellojli, Ibrahim A, Abuhallalah, Muad F, Jahan, Alhadi M, Alhadi, Abdulmueti, dra, Mohammed Abdunaser, Abdalhamed, Nadia M, Saleh, Ismail A, Albakosh, Bashir Abobaker, Hasan, Najat Ben, Bin Wali, Salema S, Hasan, Hayat Ben, Yahya, Hana B, Ambrazevicius, Marijus, Samalavicius, Narimantas E, Venskutonis, Donatas, Dauksa, Albertas, Dambrauskas, Zilvinas, Gudaityte, Rita, Dulskas, Audrius, Januška, Gediminas, Strupas, Kestutis, Poskus, Tomas, Gulla, Aiste, Caruana, Rebecca, Patel, Parth K, Ong, Ernest CW, Ahmed, Sarfraz, Yusoff, Ahmad Ramzi, Abdullah, Bahiyah, Miswan, Mohd Fairudz Mohd, Wong, Sui-Weng, Jailani, Ruhi Fadzlyana, Hakim, Nor A, Tai, Hizami Amin, Yee, Lee Fei, Yahaya, Ahmad S, Fathi, Nik Q, Voon, Kelvin, Hung, Wei Pin, Noor, Ruzaimie, Salleh, Syahrul Anuar, Ismail, Muhamad Izwan, Huei, Tan Jih, Ramely, Rosnelifaizur bin, Zakaria, Andee Dzulkarnaen, Mohamad, Ikhwan Sani, Hashim, Mohd Nizam Md, MahboobAli, Mohamed Shafi, Ab Rahman, Norhafiza, Othman, Ahmad Faidzal, Sarif, Mat Salleh, Chai, Feng Yih, Liang, Lim See, Rahim, Razrim, Subramaniam, Sentilnathan, Mah, Jin-Jiun, Hayati, Firdaus, Ibrahim, Aini Fahriza, Kuan, Yew Chor, Mahendran, Hans A, Nazimi, Abd Jabar, Imran, Farrah Hani, Ramli, Roszalina, Din, Norshamsiah M, Fai, Tang Seng, Nabil, Syed, Bastion, 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Stephen, Laoye, Adeyinka, Hussain, Abdulzahra Abdulsamad, Zafar, Muneeb, Elsheikh, Mohammed H, Shaerf, Daniel A, Soggiu, Fiammetta, Massoumi, Abaris, Gareb, Fahed, Yao, Mark W, Qamar, Mubasher A, Fang, Clarissa E H, Greenhalgh, Michael S, Hunt, Alexander, Oladeji, Emmanuel O, Benjamin, Miles W, Beak, Philip, Rae, Fraser J, Aithie, Joanna M S, Clarke, Gareth W J, Veeramootoo, Darmarajah, Ashman, Alex J, Kahka, Ehab E, Rafe, Tanvir, PATEL, PANNA K, Albirnawi, Hatim, Katory, Mark, Fisher, Ann, Amonkar, Sunil J, Rao, Pawan Kumar Dhruva, Holroyd, David J, Gkikas, Andreas, Newton, Lydia S, Kirk, Alan J B, Khalid, Ayesha, Ferguson, David, Stanier, Paul B, Shah, Vinay, El-Boghdadly, Kariem, Schizas, Alexis M P, ilyas, Minahi, George, Mark L, Gawad, Mothana, Groom, William D, Al-Azzawi, Mohammed, Ahluwalia, Julian CJ, Punjabi, Prakash P, Cheung, Fang Yi, Wilson, Michael D, Mitrofan, Claudia Gabriela, Malam, Yogeshkumar, Townson, Adam, Loubani, Mahmoud, Yau, Jih Dar, Seebah, Kevin, Akowuah, Enoch F, Pushpoth, Sreekumari R, Viswanath, Yirupaiahgari KS, ElSanhoury, Kareem, Chew, Misha, Walker, Thomas E, Elhassan, Almutasim Billah Elbagir, Belcher, Elizabeth, Goricar, Matej, majd, Hooman Soleymani, Knight, Dominic, Ismail, Lamiese, McKinnon, Chris, Ganau, Mario, Prokopenko, Max, Doshi, Neel S, Gkorila, Aikaterina, Sheikh, Nomaan A, Helm, Jessica R, Low, Mei Ken, Ogunfusika, Oluseyi Harold, Bisheet, George, Alhammali, Tariq, Arnob, Ahmed Showki, Singh, Jatinder, Allde, Emma L, Sambhwani, Sharan H, Dube, Manas, Gemmill, Elizabeth H, John, Joby, Gerogiannis, Ioannis N, Abuelgasim, Mona A A, Crate, Georgina, Holme, Thomas J, Nguyen, Anh T V, Ho, Michael W, Wade, Ryckie G, Hussain, Azar, Andrzejowski, Paul, Omakobia, Eugene, Eltayeb, Momin, Galabov, Tsanko P, Lee, Chung Yan Vernon, Nazir, Anum, Siaw, Oliver L, Ashford, Robert U, Boddy, Alex P, Ashmore, Christopher D, Shah, Snehadhar M, Gowers, Benjamin T V, Thekkinkattil, Dinesh K, Worku, Dawit, Harky, Amer, Talwar, Rishi, Sagoo, Harkiran K, Jambulingam, Periyathambi S, Smart, Christopher J, Doherty, Daniel T, Mastoridis, Sotiris, Kumar, Sidharth, Mahmoud, Rana, Solari, Francesca, Egan, Richard J, Barry, Jonathan D, Morrison, Jo, Davoudi, Kaveh, Hollyman, Marianne, Kelly, Andrew, Badenoch, Thomas F, pandanaboyana, sanjay, Critchley, Rebecca J, Sarodaya, Varun R, Sinnerton, Robert J H, Manickavasagam, Jaiganesh, Lindsay, Elizabeth F, Arora, Ankita, Hasan, Raashad, Liew, Ignatius, Ozua, Joshua, Kouritas, Vasileios, Collins, Rachael V, Lafford, George H, Moret, Charlie, Chean, Chung Shen, Horgan, Liam F, Aujayeb, Avinash, Siddique, Muhammad Harris, Navaratne, Lalin, Kotecha, Sanjeev, Bellato, Vittoria, Lewis, Sophia E, Ali, Muhammad Usman, Marson, Ben A, Craxford, Simon, Gajjar, Ketankumar, Theophilidou, Elena, Aboelmagd, Tariq, Khatkar, Harman, Awadallah, Mahmoud A, Blanco, Jose A, Chituku, Tsitsi G, Dixon, Oliver GB, sarveswaran, Janahan, Jones, Imogen S, Hammouche, Salah, Vijay, Vardhini, Ooi, Rucira, Karmarkar, Rahi, Khaleeq, Tahir, Bhatia, Mohit, Al-Khazaali, Badr L, Daadipour, Audrina, Mattar, Ahmed, Singhal, Tarun, Mahmoud, Moustafa Ibrahim, Glasbey, James, Nankivell, Paul C, Kalkat, Maninder S, Nour, Shahd, Beggs, Andrew D, Yershov, Danylo Y, Chughtai, Shafiq Ahmad, Youssef, Hesham, Norrish, Alan R, Mohammed, Mohammed M, Gwozdz, Adam M, Charalambous, Michalis P, Knight, Stephen R, McCaul, James A, Bridgman, Elsie A, El Sheikh, Mustafa, Ogunbowale, Akinsola, Wright, Evan O, Ahmed, Usama, Younus, Hafsa, Tincknell, Laura G, Weixing-Ho, Ken, Demetriou, Charis, Hussei, Mohammed, Reilly, John-Joe, Hormis, Anil P, Moug, Susan J, Anazor, Fitzgerald C, Horwell, Edward A, Neal-Smith, Gregory, McNamara, John M, Baryeh, Kwaku W, Bhatti, Khalid M, McKay, Joseph E, Cannoletta, Maria G, Perkins, Clare J, Gopalswamy, Sivakumar, Sheldon, Anna F, John, Joseph B, Mantle, Mark, Toia, Bogdan, Phillips, Andrew J, Al-Khyatt, Waleed, Lund, Jonathan N, Ammar, Ahmed Y, Yim, Guang H, Huntley, Daniel A, Daniels, Ian R, Valverde, Joao, Lumley, Edward David John, Walton, Thomas J, Raptis, Dimitri A, Dimitrokallis, Nikolaos, Nathan, Arjun, Motallebzadeh, Reza, Chowdhury, Shihab, Ahmed, Rezwan F A, Mirnezami, Reza, Szakmany, Tamas, Knight, Dominic J, Al-Azzani, Waheeb, Davies, Huw R, Ooi, Setthasorn Zhi Yang, Oo, Khaing K, Cullis, Paul S, Peng, Ed, Demetriades, Andreas K, Tambyraja, Andrew L, Poon, Michael TC, Brennan, Paul M, Oikonomou, Dimitrios, Newman, Samuel E, Le Blevec, Louise, Otify, Mohamed, Szatmary, Peter, Devkaran, Bhavesh, Sochorova, Dana, Sohrabi, Catrin, Sivaprakasam, Rajesh, Goh, Mingzheng Aaron, Atkinson, Kate V, Soares, Delvene, Prce, Daniela, Cann, Johnathon P, Grobbelaar, Amy C, Bradley, Rebecca, Strauss, Helen J, Taha, Ahmed, Minicozzi, Annamaria, Thakur, Bhaskar, Hanoun, Abdullah, Goru, Poornanand, Baumber, Rachel M, Sobti, Anshul S, Cross, George WV, Havenhand, Tom, Antoniou, George A, Chauhan, Govind Singh, Vokshi, Ismail, Mahmud, Ayesha, Albanese, Erminia, Evans, Daisy, Madhuri, Thumuluru Kavitha, Horsnell, Jonathan D, Zalmay, Pardis, Davies, Angharad J, Aljanadi, Firas, Jeganathan, Reubendra, Jones, Mark, Kakos, Christos, vidya, Raghavan, El-Ghobashy, Alaa, Habib, Ahmed M, Reid, Jeremy P, Rajgor, Harshadkumar Dhirajlal, Ahmed, Omar, Branagan, Graham, Mohamedahmed, Ali Yasen Y, Al-Sabbagh, Ali, Chetty, Govind, Kelty, Clive J, EL-Wajeh, Yasin A M, Tomlinson, James E, Rominiyi, Ola, Sinha, Saurabh, Saad, Sanad, Sahu, Banchhita, Charalampakis, Vasileios, Enemosah, Ibrahim, Williams, Simon J, Yaqoob, Hassan N, Laurent, Edward P, Moreau, Joshua L, Frostick, Rhiannon, Parwaiz, Hammad, Aboelmagd, Karim, Pournaras, Dimitri J, Hristova, Kalina H, Iyengar, Karthikeyan P, Mohamed, Muyed, Artioukh, Dmitri Y, Anwar, Sibtain, Hussein, Mostafa K A, Omogbehin, Tomisin S, Herron, Jonathan B T, Labib, Amir, Patel, Preemal, Marsden, Samuel C, Mehdian, Roshana, Santhirakumaran, Gowthanan, Smelt, Jeremy, Agarwal, Ketan, Lancerotto, Luca, Sahnan, Kapil, Shalhoub, Joseph, Donnelly, Liam J, Erridge, Simon, Chidambaram, Swathikan, Luo, Xun, Bansal, Sujesh, Ryan, Neil AJ, Smith, Alexander C D, Flatman, Michael, Wafaie, Imad, Malik, Muhammad Isfandyar Khan, Thumbadoo, Ruben P, Hussain, Shoaib F, Henein, Christin, Hamad, Yousif T, Belgaumkar, Ajay P, Bosanquet, David C, Kolias, Angelos G, Choi, David, Marcus, Hani J, Horsfall, Hugo RM Layard, Khan, Danyal Z, Sahni, Arun, Millward, Christopher P, Render, Luke, Truss, Adam, Elmoslemany, Tarek, Parmar, Chetan, Hanger, Joseph, Sheen, Jonathon, Rait, Jaideep S, Foreman, Jennifer, Marzouqa, Natalie, Fontalis, Andreas, Voulalas, Grigorios, CHEONG, Ryan Chin Taw, Dindyal, Sanjay, Arumugam, Sathyaseelan, Ward, Thomas R W, Stephens, Alastair S, Douka, Eleftheria, Abou-Foul, Ahmad K, McKay, Siobhan C, Kitchen, Mark O, Rees-Stoner, Oliver DJ, Balasubramanya, Supriya, Akhtar, Muhammad Adeel, Warwick, Andrew J, Pawar, Shweta, Dubey, Vivek, Al-Yaseen, Mustafa W, Williams, Christopher YK, Laird, Alexander, Krishna, Kandaswamy, Anyaugo, Ngozi S, Wuraola, Obafemi K, Odejinmi, Funlayo, Craven, Joanna M, West, Charlotte L, Barter, Reece A, Navaratnam, Devaraj M, Malik, Shahbaz S, Mahendran, Vimaladhithan, Zilvetti, Miguel, Lovegrove, Richard E, Board, Tim N, Zeiton, Moez, Sarwar, Safdar A, Duff, Sarah E, Hsabo, Elmuiz A, Nugur, Ashwani Kumar, Morris, Richard M, Lala, Anil K, Kwan-Feinberg, Rita O, Ross, Samuel W, Dressler, Jeremy A, Evans, Faye M, Wason, Shaun E L, Vogel, Keianna R, Wang, Joanna C, Sulciner, Megan L, Hirji, Sameer, Raoof, Mustafa, Wolff, Christopher J, kent, Ilan, Turan, Alparslan, Teixeira, Pedro G, Olson, Kristofor A, Patel, Neil D, Krishnamoorthy, Vijay, Moris, Dimitrios, Rice, Henry E, Gabr, Hesham, Satoskar, Savni R, Castater, Christine A, Jmaileh, Manal, Payne, Rachel E, Kwon, David S, Aarabi, Shahram, Escobar, Pedro F, Kronenfeld, Joshua P, Dalton, Michael K, Etchill, Eric W, Haut, Elliott R, Vervoort, Dominique, Dehal, Ahmed, McKenney, Mark, Elkbuli, Adel, Gosain, Ankush, Abdelsattar, Zaid M, Naunheim, Matthew R, Burks, Ciersten A, Zhou, Allen S, Heng, Marilyn, Abohashem, Shady, Lozano-Calderón, Santiago A, Reisenauer, Janani S, Mouawad, Nicolas J, Diehl, Thomas M, Eriksson, Evert A, Marwaha, Jayson S, Schroeppel, Thomas J, LaRocca, Christopher J, Chang, Grace H, Hassan, Romana, Nosanov, Lauren B, Rickard, Jennifer L, Avraham, Jacob B, Petrone, Patrizio, Sferra, Joseph J, Hadaya, Joseph, Mead, Brittany S, Hauptman, Jason S, Ahmad, Maleeha, Meola, Antonio, Chang, Steven D, Ko, Ara, Specht, Katherine E, Choudhry, Asad, Encalada, Ronald Zerna, Poggio, Juan L, Xing, Hang, Glass, Nina E, Hooker, Robert, Martins, Paulo N, Scott, Erin M, Bankhead, Brittany K, Giorgakis, Emmanouil, Nigh, Joe, Osborn, Tamara, Tay Lasso, Erika L, Beswick, Daniel M, Berndtson, Allison E, Kaups, Krista L, Chen, Lee-lynn, Farrell, Michael S, Boeck, Marissa A, Vaysburg, Dennis M, Kassam, Al-Faraaz, Turner, Kevin M, Dyas, Adam R, Coleman, Julia R, Folsom, Megan, Lam, Christopher M, Kumer, Sean C, Larson, Kelsey, Turner, Scott, Guidry, Christopher, Reddy, Madhuri, Berbel, German, Findley, Austin, Beahm, David, Bur, Andres, Marlor, Derek, Houndschell, Corey, Carver, Shea, Ulrich, Alissa, Bhutiani, Neal, DiChiacchio, Laura, Abdou, Hossam, Napolitano, Lena M, Ghebre, Rahel, Bass, Gary Alan, Kaplan, Lewis J, Martin, Niels D, Duffy, Caoimhe C, Abdelhamid, Sultan S, Daley, Brian J, Roland, Christina L, Dumas, Ryan P, Ban, Vin Shen, Rajesh, Aashish, Davies, Mark G, Purudappa, Prabhudev P, Walters, Camila B, Lin, Nicole, Ruzgar, Nensi M, Ullrich, Sarah J, Trostchansky, Ivan, Bonilla-Cal, Fernando, Castedo, Fabiola, Sobrero, Helena, Acuña, Gastón, Álvarez, Sofía M, Tarigo, Josefina, Carbajal, Ana C, Carbajal, Ana, Reyes, Antonio R, Al-Eryani, Fatima A, Alqousi, Nardeen N, Alattas, Zainab, Al-Saban, Rafat A, Al-Shehari, Mohammed M, ALHammadi, Nawal T, Shream, Sarah A, Al-Naggar, Hamza M, Al-Qalisi, Lina M, Nadeesh, Areej E, Al-Samawi, Hytham H, Bajjah, Hadeel M, AL-Ameri, Saba A, Albably, Jamal F, Ghannam, Rana A, Shamsan, Amatallah H, Meead, Abdullah A, Al- Zubaidi, Riham Q, Zulait, Mohammed A, Najeeb, Halah, Alsayadi, Musaed M, Al-Mashreqi, Seham K, Al-Jomai, Najla A, Alsayadi, Ramzi A, Al-Naggar, Moath M, Almarashi, Hassan A, Musaeed, Hasna M, Al-Raimi, Ibrahim M, Ghanem, Hossam N, Al-Zazay, Karim A, AL-Mahdi, Shehab A, Almontaser, Amatalaleem S, Savopoulos, Vanessa A S, Munthali, James, Kabongo, Kizito M C, Mushiwokufa, Willard, Ngulube, Allan, Ntoto, Crispin, Magama, Praise T, Dzinotyiwei, Daniel, Chivanga, Shelton K, Dube, Ngqabutho S, Sanchez, Ernesto C, Moyo, Assel T, Chengahomwe, Antony, Chinyowa, Simbarashe, Siamuchembu, Maphios, Bondera, Tafadzwa, and Mushawarima, Trust
Published: 2022
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37. A New Class of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p$$\end{document}-Adic Lipschitz Functions and Multidimensional Hensel’s Lemma

Author: León-Cardenal, Edwin, Jaime Rodriguez-Vega, John, and Bolivar-Barbosa, Fausto
Published: 2022
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38. TeNDER: towards efficient Health Systems through e-Health platforms employing multimodal monitoring.

Author: Vassilis Solachidis, Jaime Rodriguez Moreno, Gustavo Hernández-Peñaloza, Nicholas Vretos, Federico álvarez, and Petros Daras
Published: 2021
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39. Differentiation of tumor-associated fibroblasts from prostate cancer stem cells obtained from prostate tumors

Author: Flores Islas, A.K., primary, Rico Fuentes, C., additional, Sierra Diaz, E., additional, Castro Zazueta, S., additional, Jaime Rodriguez, M., additional, Villegas Pineda, J.C., additional, Garcia Chagollan, M., additional, Vega Magaña, N., additional, Peña Rodriguez, M., additional, Ramos Solano, M., additional, Zepeda Nuño, S., additional, Pereira Suarez, A.L., additional, and Ramirez De Arellano, A., additional
Published: 2024
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40. Problemas de la profesión (Desde el punto de vista de un arquitecto con menos de diez años de ejercicio)

Author: Jaime Rodriguez V.
Subjects: Aesthetics, BH1-301, Philosophy (General), B1-5802
Abstract: No presenta resumen
Published: 1969

41. Subduction-related Jurassic volcanism in the Mesa Central province and contemporary Gulf of Mexico opening

Author: Barboza-Gudiño, José Rafael, Zavala-Monsiváis, Aurora, Castellanos-Rodríguez, Valentina, Jaime-Rodríguez, Diego, and Almaraz-Martínez, Carolina
Published: 2021
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42. STEM CELL THERAPY FOR MEN'S VITALITY: A COMPREHENSIVE REVIEW AND META-ANALYSIS.

Author: Vinski, Deby Susanti Pada, Quintosa, Jaime Rodriguez, Trofimova, Svetlana, Nugroho, Andi Kurniawan, Vinski, Natasha Cinta, and Hardjo, Marhaen
Subjects: *STEM cell treatment, *MESENCHYMAL stem cells, *MEN'S health, *RANDOMIZED controlled trials, *REGENERATIVE medicine
Abstract: Stem cell therapy has shown significant potential to enhance men's vitality by addressing conditions like erectile dysfunction (ED) and hypogonadism. This comprehensive review and meta-analysis aim to evaluate the efficacy, safety, and mechanisms of stem cell therapy in improving male sexual health and vitality. The study draws from clinical trials, reviews, and preclinical studies, focusing on mesenchymal stem cells (MSCs) and their ability to regenerate tissues, improve erectile function, and boost testosterone levels. A metaanalysis with random-effects models was employed to assess these outcomes alongside the anti-inflammatory properties of MSCs, which play a crucial role in tissue repair and immune modulation. The findings demonstrate that stem cell therapy significantly enhances erectile function, increases testosterone levels, and improves sperm quality. However, the study also highlights several limitations, including heterogeneity among the studies, lack of long-term data, and the absence of standardized treatment protocols. These factors limit the ability to draw definitive conclusions regarding the therapy's broader applicability. Despite these limitations, stem cell therapy holds promise as a novel approach to regenerative medicine, offering innovative solutions for men's health and vitality. Future research should focus on conducting large-scale randomized controlled trials with standardized protocols to validate the long-term efficacy and safety of stem cell therapy in treating male sexual health disorders and improving overall quality of life. [ABSTRACT FROM AUTHOR]
Published: 2024

43. Differential response to Cadmium exposure by expression of a two and a three-domain metallothionein isoform in the land winkle Pomatias elegans: Valuating the marine heritage of a land snail

Author: Schmielau, Lara, Dvorak, Martin, Niederwanger, Michael, Dobieszewski, Nicole, Pedrini-Martha, Veronika, Ladurner, Peter, Pedregal, Jaime Rodríguez-Guerra, Maréchal, Jean-Didier, and Dallinger, Reinhard
Published: 2019
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44. Reputation Computational Model to Support Electricity Market Players Energy Contracts Negotiation.

Author: Jaime Rodriguez-Fernandez, Tiago Pinto, Francisco Silva 0001, Isabel Praça, Zita A. Vale, and Juan Manuel Corchado
Published: 2018
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45. 739 - UNIDAD DE DIAGNÓSTICO RÁPIDO-ADENOPATÍAS: ETIOLOGÍA Y CRITERIOS DE RIESGO

Author: López-Mosteiro, Alejandra Franquet, Tosar, Julia Urpí, Aranda, Mariano Pascual, Vives, Eloy García, Arnau, Ariadna Brase, Morera, Jaime Rodríguez, Esquius, María Lourdes Cos, and Solan, Xavier Nogués
Published: 2024
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46. Four-Switch Three-Phase Operation of Grid-Side Converter of Doubly Fed Induction Generator With Three Vectors Predictive Direct Power Control Strategy.

Author: Mohammad Ebrahim Zarei, Carlos Veganzones Nicolas, Jaime Rodriguez Arribas, and Dionisio Ramírez
Published: 2019
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47. Doppler spectrum measurements of vehicular radio channels using a narrowband sounder/Mediciones de espectro Doppler de canales de radio vehicular usando un sondeador de banda angosta

Author: Gomez-Vega, Carlos A., Gutierrez, Carlos A., Jaime-Rodriguez, Jose J., Castillo, Javier Vazquez, Campos-Delgado, Daniel U., Luna-Rivera, Jose M., and Diaz-Ibarra, Miguel A.
Published: 2019
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48. Grid-tied Multilevel Inverter with Phase-locked Loop Algorithm/Inversor multinivel enlazado a la red electrica mediante un algoritmo de fijacion de fase/Inversor multinivel ligado a rede eletrica atraves de um algoritmo de fixacao de fase

Author: Martinez-Montejano, Roberto, Alvarez-Maldonado, Osbaldo-Ulisses, Jaime-Rodriguez, Jose-Jimmy, Gonzalez-Badillo, Germanico, Campos-Canton, Isaac, and Martinez-Montejano, Misael-Francisco
Published: 2022
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49. Epitope Lability of Phosphorylated Biomarkers of the DNA Damage Response Pathway Results in Increased Vulnerability to Effects of Delayed or Incomplete Formalin Fixation

Author: Elizabeth J. Wiseman, Jennifer I. Moss, James Atkinson, Hana Baakza, Emily Hayes, Sophie E. Willis, Paul M. Waring, Jaime Rodriguez Canales, and Gemma N. Jones
Subjects: Histology, Anatomy
Abstract: Phosphorylated biomarkers are crucial for our understanding of drug mechanism of action and dose selection during clinical trials, particularly for drugs that target protein kinases, such as DNA-damage-response (DDR) inhibitors. However, tissue fixation conditions needed to preserve DDR-specific phospho-biomarkers have not been previously investigated. Using xenograft tissues and tightly controlled formalin fixation conditions, we assessed how preanalytical factors affect phosphorylated DDR biomarkers pRAD50(Ser635), ɣH2AX(Ser139), pKAP1(Ser824), and non-phosphorylated biomarkers cMYC and ATM. Cold ischemia times ranged from 15 min to 6 hr, and the fixation duration ranged from 24 hr to 4 weeks. Epitopes pRAD50 and pKAP1 appeared the most labile assessed with staining loss after just 15 min of cold ischemia time, while ATM was more robust showing consistent expression up to 1 hr of cold ischemia. Notably, ɣH2AX expression was lost with formalin fixation over 48 hr. The use of core needle biopsies where possible and novel fixation methods such as the 2-step temperature-controlled formalin approach may improve phosphorylated biomarker preservation; however, practical challenges may affect wider clinical application. The most essential tissue-processing step when downstream analysis includes DDR phosphorylated biomarkers is immediate tissue submersion in formalin, without delay, upon excision from the patient, followed by room temperature fixation for 24 hr.
Published: 2023
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50. Predicción matemática de la relación marginal capital producto anual con base en una metodología fundamentada en la caminata al azar probabilística

Author: Jose Reyes Bernal-Bellon, Jaime Rodriguez, Javier Oswaldo Rodriguez Velasquez, Sandra Catalina Correa Herrera, Signed Esperanza Prieto Bohorquez, and Jorge Eliecer Gaitan Mendez
Subjects: General Economics, Econometrics and Finance
Published: 2023
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