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Article ; Online: Anthracyclines induce cardiotoxicity through a shared gene expression response signature.

Matthews, E Renee / Johnson, Omar D / Horn, Kandace J / Gutiérrez, José A / Powell, Simon R / Ward, Michelle C

2024 Volume 20, Issue 2, Page(s) e1011164

Abstract: TOP2 inhibitors (TOP2i) are effective drugs for breast cancer treatment. However, they can cause cardiotoxicity in some women. The most widely used TOP2i include anthracyclines (AC) Doxorubicin (DOX), Daunorubicin (DNR), Epirubicin (EPI), and the ... ...

Abstract	TOP2 inhibitors (TOP2i) are effective drugs for breast cancer treatment. However, they can cause cardiotoxicity in some women. The most widely used TOP2i include anthracyclines (AC) Doxorubicin (DOX), Daunorubicin (DNR), Epirubicin (EPI), and the anthraquinone Mitoxantrone (MTX). It is unclear whether women would experience the same adverse effects from all drugs in this class, or if specific drugs would be preferable for certain individuals based on their cardiotoxicity risk profile. To investigate this, we studied the effects of treatment of DOX, DNR, EPI, MTX, and an unrelated monoclonal antibody Trastuzumab (TRZ) on iPSC-derived cardiomyocytes (iPSC-CMs) from six healthy females. All TOP2i induce cell death at concentrations observed in cancer patient serum, while TRZ does not. A sub-lethal dose of all TOP2i induces limited cellular stress but affects calcium handling, a function critical for cardiomyocyte contraction. TOP2i induce thousands of gene expression changes over time, giving rise to four distinct gene expression response signatures, denoted as TOP2i early-acute, early-sustained, and late response genes, and non-response genes. There is no drug- or AC-specific signature. TOP2i early response genes are enriched in chromatin regulators, which mediate AC sensitivity across breast cancer patients. However, there is increased transcriptional variability between individuals following AC treatments. To investigate potential genetic effects on response variability, we first identified a reported set of expression quantitative trait loci (eQTLs) uncovered following DOX treatment in iPSC-CMs. Indeed, DOX response eQTLs are enriched in genes that respond to all TOP2i. Next, we identified 38 genes in loci associated with AC toxicity by GWAS or TWAS. Two thirds of the genes that respond to at least one TOP2i, respond to all ACs with the same direction of effect. Our data demonstrate that TOP2i induce thousands of shared gene expression changes in cardiomyocytes, including genes near SNPs associated with inter-individual variation in response to DOX treatment and AC-induced cardiotoxicity.
MeSH term(s)	Humans ; Female ; Anthracyclines/adverse effects ; Anthracyclines/metabolism ; Cardiotoxicity/genetics ; Cardiotoxicity/metabolism ; Antibiotics, Antineoplastic/adverse effects ; Antibiotics, Antineoplastic/metabolism ; Topoisomerase II Inhibitors/metabolism ; Topoisomerase II Inhibitors/pharmacology ; Doxorubicin/adverse effects ; Doxorubicin/metabolism ; Mitoxantrone/adverse effects ; Mitoxantrone/metabolism ; Myocytes, Cardiac/metabolism ; Daunorubicin/metabolism ; Daunorubicin/pharmacology ; Epirubicin/metabolism ; Epirubicin/pharmacology ; DNA Topoisomerases, Type II/genetics ; Gene Expression
Chemical Substances	Anthracyclines ; Antibiotics, Antineoplastic ; Topoisomerase II Inhibitors ; Doxorubicin (80168379AG) ; Mitoxantrone (BZ114NVM5P) ; Daunorubicin (ZS7284E0ZP) ; Epirubicin (3Z8479ZZ5X) ; DNA Topoisomerases, Type II (EC 5.99.1.3)
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1011164
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Numerical Representation of Groundwater-Surface Water Exchange and the Effect on Streamflow Contribution Estimates

Karan, Sachin / Jacobsen, Martin / Kazmierczak, Jolanta / Reyna-Gutiérrez, José A. / Breum, Thomas / Engesgaard, Peter

Water. 2021 July 12, v. 13, no. 14

2021

Abstract: The effects of streams and drainage representation in 3D numerical catchment scale models on estimated streamflow contribution were investigated. MODFLOW-USG was used to represent complex geology and a stream network with two different conceptualizations— ...

Abstract	The effects of streams and drainage representation in 3D numerical catchment scale models on estimated streamflow contribution were investigated. MODFLOW-USG was used to represent complex geology and a stream network with two different conceptualizations—one with equal cell discretization in the entire model domain and another with refined cell discretization along stream reaches. Both models were calibrated against a large data set including hydraulic heads and streamflow measurements. Though the optimized hydraulic parameters and statistical performance of both model conceptualizations were comparable, their estimated streamflow contribution differed substantially. In the conceptualization with equal cell discretization, the drainage contribution to the streamflow was 13% compared to 41% in the conceptualization with refined cell discretization. The increase in drainage contribution to streamflow was attributed to the increase in drainage area in proximity to the stream reaches arising from the refined discretization. e.g., the cell refinement along stream reaches reduced the area occupied by stream cells allowing for increased drain area adjacent to the stream reaches. As such, an increase in drainage area equivalent to 7% yielded a 146% increase in drainage contribution to streamflow. In-stream field measurements of groundwater-surface water exchange fluxes that were qualitatively compared to calculated fluxes from the models indicated that estimates from the refined model discretization were more representative. Hence, the results of this study accentuate the importance of being able to represent stream and drain flow contribution correctly, that is, to achieve representative exchange fluxes that are crucial in simulating groundwater–surface water exchange of both flow and solute transport in catchment scale modeling. To that end, the in-stream measurements of exchange fluxes showed the potential to serve as a proxy to numerically estimate drainage contribution that is not readily available at the catchment scale.
Keywords	data collection ; drainage ; solutes ; stream flow ; streams ; water ; watersheds
Language	English
Dates of publication	2021-0712
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2521238-2
ISSN	2073-4441
ISSN	2073-4441
DOI	10.3390/w13141923
Database	NAL-Catalogue (AGRICOLA)

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Book: Low-rate wireless personal area networks

Gutiérrez, José A

enabling wireless sensors with IEEE 802.15.4

(IEEE standards wireless networks series)

2010

Author's details	José A. Gutiérrez ... [et al.]
Series title	IEEE standards wireless networks series
Keywords	Personal area networks (Computer networks) ; Sensor networks ; Wireless LANs
Language	English
Size	xxxiii, 245 p, ill, 23 cm
Edition	3rd ed
Publisher	Standards Information Network, IEEE Press
Publishing place	Piscataway, N.J.
Document type	Book
Note	Includes bibliographical references and index ; Rev. ed. of: Low-rate wireless personal area networks / José A. Gutiérrez, Edgar H. Callaway, Jr., Raymond L. Barrett, Jr. 2007
ISBN	073816285X ; 9780738162850
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article: Pharmacokinetics of enrofloxacin HCl‐2H2O (ENRO‐C), PK/PD, and Monte Carlo modeling vs. Leptospira spp. in cows

Mendoza, Jesús / Gutierrez, Lilia / Gutiérrez, José Á / Bustos, Felipe A / Sumano, Hector

Journal of veterinary pharmacology and therapeutics. 2019 May, v. 42, no. 3

2019

Abstract: The pharmacokinetics, PK/PD ratios, and Monte Carlo modeling of enrofloxacin HCl‐2H2O (Enro‐C) and its reference preparation (Enro‐R) were determined in cows. Fifty‐four Jersey cows were randomly assigned to six groups receiving a single IM dose of 10, ... ...

Abstract	The pharmacokinetics, PK/PD ratios, and Monte Carlo modeling of enrofloxacin HCl‐2H2O (Enro‐C) and its reference preparation (Enro‐R) were determined in cows. Fifty‐four Jersey cows were randomly assigned to six groups receiving a single IM dose of 10, 15, or 20 mg/kg of Enro‐C (Enro‐C10, Enro‐C15, Enro‐C20) or Enro‐R. Serial serum samples were collected and enrofloxacin concentrations quantified. A composite set of minimum inhibitory concentrations (MIC) of Leptospira spp. was utilized to calculate PK/PD ratios: maximum serum concentration/MIC (Cmax/MIC90) and area under the serum vs. time concentration of enrofloxacin/MIC (AUC0‐24/MIC90). Monte Carlo simulations targeted Cmax/MIC = 10 and AUC0‐24/MIC = 125. Mean Cmax obtained were 6.17 and 2.46 μg/ml; 8.75 and 3.54 μg/ml; and 13.89 and 4.25 μg/ml, respectively for Enro‐C and Enro‐R. Cmax/MIC90 ratios were 6.17 and 2.46, 8.75 and 3.54, and 13.89 and 4.25 for Enro‐C and Enro‐R, respectively. Monte Carlo simulations based on Cmax/MIC90 = 10 indicate that only Enro‐C15 and Enro‐C20 may be useful to treat leptospirosis in cows, predicting a success rate ≥95% when MIC50 = 0.5 μg/ml, and ≥80% when MIC90 = 1.0 μg/ml. Although Enro‐C15 and Enro‐C20 may be useful to treat leptospirosis in cattle, clinical trials are necessary to confirm this proposal.
Keywords	Jersey ; Leptospira ; Monte Carlo method ; blood serum ; cattle diseases ; clinical trials ; cows ; enrofloxacin ; leptospirosis ; minimum inhibitory concentration ; pharmacokinetics ; prediction
Language	English
Dates of publication	2019-05
Size	p. 300-308.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	435216-6
ISSN	1365-2885 ; 0140-7783
ISSN (online)	1365-2885
ISSN	0140-7783
DOI	10.1111/jvp.12748
Database	NAL-Catalogue (AGRICOLA)

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Article: Social life cycle assessment methodology for evaluating production process design: Biorefinery case study

Carvalho, Ana / Cadena, Erasmo / Gutierrez, Jose A / Rocca, Francesco

Journal of cleaner production. 2019 July 20,

2019

Abstract: Social Life Cycle Assessment (S-LCA) is a methodological approach to evaluating the positive and negative social impacts of a product or a service throughout its life cycle. The scope of conducting an S-LCA is to promote social conditions and the overall ...

Abstract	Social Life Cycle Assessment (S-LCA) is a methodological approach to evaluating the positive and negative social impacts of a product or a service throughout its life cycle. The scope of conducting an S-LCA is to promote social conditions and the overall socio-economic performance of a product for all its stakeholders; leading to a holistic approach, where different stakeholders, with diverse interests are involved. At production process design, the stakeholders’ knowledge and engagement in the system are very limited, and data is not available to assess social aspects. Therefore, S-LCA applied to the early stage of production process design is a highly complicated task, but at the same time, it is a top priority to ensure proper social conditions when the process is implemented. There is a lack of systematic and quantitative methodologies that guide practitioners in the S-LCA appliance. This work aims to propose a new methodology to S-LCA for production process design assessment. As an example of application, the suggested approach was applied to a production process design of a biorefinery project located in the Netherlands. This case study reflects the actual worldwide concern regarding the social distress, environmental impacts of dependence on fossil-based fuels, development and the promotion of bio-based processes across supply chains. Biorefineries appear as a cornerstone in the field promoting the replacement of fossil-based resources by biomass raw materials, which are then transformed into a different bio-based product, namely chemicals, fuels and power. As a result, the methodology provided a preliminary overview of the potential social hotspots found along the biorefinery life-cycle, which should be considered when implementing the project.
Keywords	biofuels ; biomass ; biorefining ; case studies ; distress ; environmental impact ; fossil fuels ; life cycle assessment ; process design ; raw materials ; social impact ; socioeconomics ; stakeholders ; supply chain ; Netherlands
Language	English
Dates of publication	2019-0720
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ISSN	0959-6526
DOI	10.1016/j.jclepro.2019.117718
Database	NAL-Catalogue (AGRICOLA)

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Article: Context-free hyperspectral image enhancement for wide-field optical biomarker visualization.

Pardo, Arturo / Gutiérrez-Gutiérrez, José A / López-Higuera, José M / Conde, Olga M

Biomedical optics express

2019 Volume 11, Issue 1, Page(s) 133–148

Abstract: Many well-known algorithms for the color enhancement of hyperspectral measurements in biomedical imaging are based on statistical assumptions that vary greatly with respect to the proportions of different pixels that appear in a given image, and thus may ...

Abstract	Many well-known algorithms for the color enhancement of hyperspectral measurements in biomedical imaging are based on statistical assumptions that vary greatly with respect to the proportions of different pixels that appear in a given image, and thus may thwart their application in a surgical environment. This article attempts to explain why this occurs with SVD-based enhancement methods, and proposes the separation of spectral enhancement from analysis. The resulting method, termed
Language	English
Publishing date	2019-12-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2572216-5
ISSN	2156-7085
ISSN	2156-7085
DOI	10.1364/BOE.11.000133
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Article ; Online: Custom Scanning Hyperspectral Imaging System for Biomedical Applications: Modeling, Benchmarking, and Specifications.

Gutiérrez-Gutiérrez, José A / Pardo, Arturo / Real, Eusebio / López-Higuera, José M / Conde, Olga M

Sensors (Basel, Switzerland)

2019 Volume 19, Issue 7

Abstract: Prototyping hyperspectral imaging devices in current biomedical optics research requires taking into consideration various issues regarding optics, imaging, and instrumentation. In summary, an ideal imaging system should only be limited by exposure time, ...

Abstract	Prototyping hyperspectral imaging devices in current biomedical optics research requires taking into consideration various issues regarding optics, imaging, and instrumentation. In summary, an ideal imaging system should only be limited by exposure time, but there will be technological limitations (e.g., actuator delay and backlash, network delays, or embedded CPU speed) that should be considered, modeled, and optimized. This can be achieved by constructing a multiparametric model for the imaging system in question. The article describes a rotating-mirror scanning hyperspectral imaging device, its multiparametric model, as well as design and calibration protocols used to achieve its optimal performance. The main objective of the manuscript is to describe the device and review this imaging modality, while showcasing technical caveats, models and benchmarks, in an attempt to simplify and standardize specifications, as well as to incentivize prototyping similar future designs.
MeSH term(s)	Biomedical Research/trends ; Humans ; Image Processing, Computer-Assisted/methods ; Molecular Imaging/instrumentation ; Optics and Photonics/instrumentation
Language	English
Publishing date	2019-04-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s19071692
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Article ; Online: Pharmacokinetics of enrofloxacin HCl-2H

Mendoza, Jesús / Gutierrez, Lilia / Gutiérrez, José Á / Bustos, Felipe A / Sumano, Hector

Journal of veterinary pharmacology and therapeutics

2019 Volume 42, Issue 3, Page(s) 300–308

Abstract: The pharmacokinetics, PK/PD ratios, and Monte Carlo modeling of enrofloxacin HCl- ... ...

Abstract	The pharmacokinetics, PK/PD ratios, and Monte Carlo modeling of enrofloxacin HCl-2H
MeSH term(s)	Animals ; Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/blood ; Anti-Bacterial Agents/pharmacokinetics ; Cattle ; Cattle Diseases/drug therapy ; Cattle Diseases/microbiology ; Dose-Response Relationship, Drug ; Enrofloxacin/administration & dosage ; Enrofloxacin/blood ; Enrofloxacin/pharmacokinetics ; Female ; Injections, Intramuscular ; Leptospira/drug effects ; Leptospirosis/drug therapy ; Leptospirosis/veterinary ; Microbial Sensitivity Tests/veterinary ; Monte Carlo Method
Chemical Substances	Anti-Bacterial Agents ; Enrofloxacin (3DX3XEK1BN)
Language	English
Publishing date	2019-02-03
Publishing country	England
Document type	Journal Article
ZDB-ID	435216-6
ISSN	1365-2885 ; 0140-7783
ISSN (online)	1365-2885
ISSN	0140-7783
DOI	10.1111/jvp.12748
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Article: Therapy of childhood acute lymphoblastic leukemia in resource-poor geospaces.

Gallardo-Pérez, Moisés M / Gale, Robert Peter / Reyes-Cisneros, Oscar A / Sánchez-Bonilla, Daniela / Fernández-Gutiérrez, José A / Stock, Wendy / Murrieta-Álvarez, Iván / Olivares-Gazca, Juan Carlos / Ruiz-Delgado, Guillermo J / Fonseca, Rafael / Ruiz-Argüelles, Guillermo J

Frontiers in oncology

2023 Volume 13, Page(s) 1187268

Abstract: The therapy of children with acute lymphoblastic leukemia (ALL) in limited resource geospaces is challenging and must balance safety, efficacy, availability, and affordability. We modified the control arm of the St. Jude Total XI protocol for outpatient ... ...

Abstract	The therapy of children with acute lymphoblastic leukemia (ALL) in limited resource geospaces is challenging and must balance safety, efficacy, availability, and affordability. We modified the control arm of the St. Jude Total XI protocol for outpatient delivery including once-weekly daunorubicin and vincristine in initial therapy, postponing intrathecal chemotherapy until day 22, prophylactic oral antibiotics/antimycotics, use of generic drugs, and no central nervous system (CNS) radiation. Data were interrogated from 104 consecutive children ≤12 years (median, 6 years [interquartile range (IQR), 3, 9 years]. All therapies were given in an outpatient setting in 72 children. Median follow-up is 56 months (IQR 20, 126 months). A total of 88 children achieved a hematological complete remission. Median event-free survival (EFS) is 87 months [95% confidence interval (CI), 39, 60], 7.6 years in low-risk children (3.4, 8 years) whereas 2.5 years (1, 10 years) in high-risk children. The 5-year cumulative incidence of relapse (CIR) is 28% (18, 35%), 26% (14, 37%) in low-risk children and 35% (14, 52%) in high-risk children. Median survival for all subjects is not reached but must exceed 5 years. A total of 36 children relapsed at a median of 12 months (5, 23 months). Outcomes were comparable to those reported in the control arm of the Total Therapy XI study, but inferior to current treatment protocols in high-income countries. The average cost of the first 2 years of therapy was $28,500 USD compared with an average cost of approximately $150,000 USD in the US, an 80% saving. In conclusion, using an outpatient-based modification of the St. Jude Total XI protocol, we obtained good results with relatively few hospitalizations or adverse events and at a substantial saving. This model can be applied in other resource-poor geospaces.
Language	English
Publishing date	2023-06-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1187268
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Article ; Online: Long-term results of the treatment of adolescents and adults with acute lymphoblastic leukemia with a pediatric-inspired regimen delivered on an outpatient basis: A single institution experience.

García-Villaseñor, Elizabeth / Cortés, Jorge E / Reyes-Cisneros, Oscar A / Fernández-Gutiérrez, José A / Sánchez-Bonilla, Daniela / Bojalil-Álvarez, Lorena / Murrieta-Álvarez, Iván / Ruiz-Delgado, Guillermo J / Ruiz-Argüelles, Guillermo J

Leukemia research

2022 Volume 121, Page(s) 106935

Abstract: The results of treatment of adolescents and adults with acute lymphoblastic leukemia (ALL) remain unsatisfactory. Pediatric-inspired treatments seem to be related with better outcomes. 126 adolescent and adult patients with ALL were treated in a 37-year ... ...

Abstract	The results of treatment of adolescents and adults with acute lymphoblastic leukemia (ALL) remain unsatisfactory. Pediatric-inspired treatments seem to be related with better outcomes. 126 adolescent and adult patients with ALL were treated in a 37-year period with a pediatric inspired combined chemotherapy (PICC) schedule, delivered on an outpatient basis and based on the St. Jude´s TOTAL XI pediatric protocol employing vincristine, prednisone, asparaginase, daunorubicin, etoposide, cytarabine, methotrexate, mercaptopurine and triple intrathecal therapy. 80 % of patients were able to receive the initial seven-week period of induction / consolidation fully as outpatients and 77 % achieved a complete remission. In adolescents and young adults (AYAs) the median probability of overall survival (OS) was 44 months, whereas the 5-year OS was 48 %. In adults, the median probability of OS was 24 months, and the 5-year OS was 32 %. Patients with T-cell ALL did significantly worse than those with a B cell phenotype (OS at 5 years 17 versus 40 %, respectively). These figures are better than those informed in our country employing more aggressive, in-hospital schedules such as the hyper-CVAD. We found that, in AYAs and adult patients with ALL, the use of an asparaginase-containing PICC delivered on an outpatient basis renders acceptable results, better than those obtained in similar socioeconomic circumstances employing adult-oriented schedules. Additional studies are needed to assess the usefulness of these PICC treatments in adult individuals with ALL treated in underprivileged circumstances, such as those prevailing in LMIC.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Asparaginase ; Cyclophosphamide ; Cytarabine ; Daunorubicin ; Doxorubicin/therapeutic use ; Etoposide/therapeutic use ; Humans ; Mercaptopurine ; Methotrexate/therapeutic use ; Outpatients ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Prednisone ; Vincristine/therapeutic use
Chemical Substances	Cytarabine (04079A1RDZ) ; Vincristine (5J49Q6B70F) ; Etoposide (6PLQ3CP4P3) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; Mercaptopurine (E7WED276I5) ; Asparaginase (EC 3.5.1.1) ; Prednisone (VB0R961HZT) ; Methotrexate (YL5FZ2Y5U1) ; Daunorubicin (ZS7284E0ZP)
Language	English
Publishing date	2022-08-27
Publishing country	England
Document type	Journal Article
ZDB-ID	752396-8
ISSN	1873-5835 ; 0145-2126
ISSN (online)	1873-5835
ISSN	0145-2126
DOI	10.1016/j.leukres.2022.106935
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