LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 345

Search options

  1. Article: Multi-Informant Assessment of Adolescents' Social-Emotional Skills: Patterns of Agreement and Discrepancy among Teachers, Parents, and Students.

    Mudarra, María J / Álvarez-González, Beatriz / García-Salguero, Berta / Elliott, Stephen N

    Behavioral sciences (Basel, Switzerland)

    2022  Volume 12, Issue 3

    Abstract: Objectives: This study explores the patterns of agreement and discrepancy among informants (teachers, parents, and students) in the domains of the Social Emotional Skills Scale Assessment System-Social Skills Scales (SESAS-SS), which is a translation of ...

    Abstract Objectives: This study explores the patterns of agreement and discrepancy among informants (teachers, parents, and students) in the domains of the Social Emotional Skills Scale Assessment System-Social Skills Scales (SESAS-SS), which is a translation of the Social Skills Improvement System-Rating Scales (SSIS-RS) for use in Spain.
    Methods: The sample is composed of students, 88 teachers, and 98 parents from Spanish secondary schools. Inter-rater agreements have been assessed, calculating the Pearson correlation coefficients among pairs of raters, effect size indices, and intraclass correlation coefficients at the subscale and total scale level.
    Results: The convergent validity coefficients were stronger than the divergent ones, with the highest level of agreement between teachers and parents in social skills, particularly for total social skills, engagement, empathy, and communication. The patterns of discrepancies confirmed weaker agreements between teachers and parents in self-control and between parents and students in empathy. Significant differences were also found in students' estimates depending on gender.
    Conclusions: The SESAS-SS provides support for previous studies on inter-rater agreements for SS, extending the focus on the degree of agreement in the estimate of dyads of raters when considering the students' gender.
    Language English
    Publishing date 2022-02-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2651997-5
    ISSN 2076-328X
    ISSN 2076-328X
    DOI 10.3390/bs12030062
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Exposure to environmental pollutants and genetic variants related to oxidative stress and xenobiotic metabolism-Association with prostate cancer.

    Álvarez-González, Beatriz / Hernández, Antonio F / Zafra-Gómez, Alberto / Chica-Redecillas, Lucia / Cuenca-López, Sergio / Vázquez-Alonso, Fernando / Martínez-González, Luis Javier / Álvarez-Cubero, María Jesús

    Environmental toxicology and pharmacology

    2024  Volume 108, Page(s) 104455

    Abstract: This study assessed whether genetic variants coding for certain enzymes involved in xenobiotic detoxification, antioxidant defences and DNA repair, along with exposure to environmental chemicals, were associated with an increased prostate cancer (PCa) ... ...

    Abstract This study assessed whether genetic variants coding for certain enzymes involved in xenobiotic detoxification, antioxidant defences and DNA repair, along with exposure to environmental chemicals, were associated with an increased prostate cancer (PCa) risk. The study population consisted of 300 men (150 PCa cases and 150 controls) which underwent prostate biopsy as their serum prostate specific antigen (PSA) levels were greater than 4 ng/ml. Genetic variants in GSTM1, GSTP1, SOD2, CAT, GPX1, XRCC1 were determined and data for chemical exposures was obtained through a structured questionnaire and by biomonitoring in a subsample of cases and controls. High serum PSA levels were associated with a greater risk of PCa, while physical exercise appears to exert a protective effect against its development. In addition, elevated urinary levels of certain organic pollutants, such as benzo(a)pyrene (BaP), bisphenol A (BPA), and ethyl-paraben (EPB), were associated with an increased risk of PCa.
    Language English
    Publishing date 2024-04-23
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1318302-3
    ISSN 1872-7077 ; 1382-6689
    ISSN (online) 1872-7077
    ISSN 1382-6689
    DOI 10.1016/j.etap.2024.104455
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: Methotrexate Gold Nanocarriers: Loading and Release Study: Its Activity in Colon and Lung Cancer Cells.

    Álvarez-González, Beatriz / Rozalen, Marisa / Fernández-Perales, María / Álvarez, Miguel A / Sánchez-Polo, Manuel

    Molecules (Basel, Switzerland)

    2020  Volume 25, Issue 24

    Abstract: In the present study, the synthesis of gold nanoparticles (AuNPs) loaded with methotrexate (MTX) has been carried out in order to obtain controlled size and monodispersed nanocarriers of around 20 nm. The characterization study shows metallic AuNPs with ... ...

    Abstract In the present study, the synthesis of gold nanoparticles (AuNPs) loaded with methotrexate (MTX) has been carried out in order to obtain controlled size and monodispersed nanocarriers of around 20 nm. The characterization study shows metallic AuNPs with MTX polydispersed on the surface. MTX is linked by the replacement of citrate by the MTX carboxyl group. The drug release profiles show faster MTX release when it is conjugated, which leads to the best control of plasma concentration. Moreover, the enhanced release observed at pH 5 could take advantage of the pH gradients that exist in tumor microenvironments to achieve high local drug concentrations. AuNP-MTX conjugates were tested by flow cytometry against lung (A-549) and colon (HTC-116) cancer cell lines. Results for A-549 showed a weaker dose-response effect than for colon cancer ones. This could be related to the presence of folate receptors in line HTC-116 in comparison to line A-549, supporting the specific uptake of folate-conjugated AuNP-MTX by folate receptor positive tumor cells. Conjugates exhibited considerably higher cytotoxic effects compared with the effects of equal doses of free MTX. Annexin V-PI tests sustained the cell death mechanism of apoptosis, which is normally disabled in cancer cells.
    MeSH term(s) A549 Cells ; Annexin A5/metabolism ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Death/drug effects ; Cell Line, Tumor ; Colon/drug effects ; Colon/metabolism ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/metabolism ; Drug Delivery Systems/methods ; Drug Liberation/physiology ; Folic Acid/pharmacology ; Gold/chemistry ; HCT116 Cells ; Humans ; Hydrogen-Ion Concentration ; Lung/drug effects ; Lung/metabolism ; Lung Neoplasms/drug therapy ; Lung Neoplasms/metabolism ; Metal Nanoparticles/chemistry ; Methotrexate/chemistry ; Methotrexate/pharmacology ; Tumor Microenvironment/drug effects
    Chemical Substances Annexin A5 ; Antineoplastic Agents ; Gold (7440-57-5) ; Folic Acid (935E97BOY8) ; Methotrexate (YL5FZ2Y5U1)
    Language English
    Publishing date 2020-12-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules25246049
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Genetic variants of antioxidant and xenobiotic metabolizing enzymes and their association with prostate cancer: A meta-analysis and functional in silico analysis.

    Álvarez-González, Beatriz / Porras-Quesada, Patricia / Arenas-Rodríguez, Verónica / Tamayo-Gómez, Alba / Vázquez-Alonso, Fernando / Martínez-González, Luis Javier / Hernández, Antonio F / Álvarez-Cubero, María Jesús

    The Science of the total environment

    2023  Volume 898, Page(s) 165530

    Abstract: The development and progression of prostate cancer (PCa) depends on complex interactions between genetic, environmental and dietary factors that modulate the carcinogenesis process. Interactions between chemical exposures and genetic polymorphisms in ... ...

    Abstract The development and progression of prostate cancer (PCa) depends on complex interactions between genetic, environmental and dietary factors that modulate the carcinogenesis process. Interactions between chemical exposures and genetic polymorphisms in genes encoding xenobiotic metabolizing enzymes (XME), antioxidant enzymes and DNA repair enzymes have been reported as the main drivers of cancer. Thus, a better understanding of the causal risk factors for PCa will provide avenues to identify men at increased risk and will contribute to develop effective detection and prevention methods. We performed a meta-analysis on 17,518 cases and 42,507 controls obtained from 42 studies to determine whether seven SNPs and one CNV pertaining to oxidative stress, xenobiotic detoxification and DNA repair enzymes are associated with the risk of PCa (GPX1 (rs1050450), XRCC1 (rs25487), PON1 (rs662), SOD2 (rs4880), CAT (rs1001179), GSTP1 (rs1695) and CNV GSTM1). A significant increased risk of PCa was found for SOD2 (rs4880) OR
    MeSH term(s) Male ; Humans ; Antioxidants ; Xenobiotics ; Glutathione S-Transferase pi/genetics ; Genotype ; Prostatic Neoplasms/genetics ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Case-Control Studies ; X-ray Repair Cross Complementing Protein 1/genetics ; Aryldialkylphosphatase/genetics
    Chemical Substances Antioxidants ; Xenobiotics ; Glutathione S-Transferase pi (EC 2.5.1.18) ; XRCC1 protein, human ; X-ray Repair Cross Complementing Protein 1 ; PON1 protein, human (EC 3.1.8.1) ; Aryldialkylphosphatase (EC 3.1.8.1)
    Language English
    Publishing date 2023-07-13
    Publishing country Netherlands
    Document type Meta-Analysis ; Journal Article
    ZDB-ID 121506-1
    ISSN 1879-1026 ; 0048-9697
    ISSN (online) 1879-1026
    ISSN 0048-9697
    DOI 10.1016/j.scitotenv.2023.165530
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Genetic variants of antioxidant and xenobiotic metabolizing enzymes and their association with prostate cancer: A meta-analysis and functional in silico analysis

    Álvarez González, Beatriz / Porras-Quesada, Patricia / Arenas-Rodríguez, Verónica / Tamayo-Gómez, Alba / Vázquez-Alonso, Fernando / Martínez-González, Luis Javier / Hernández, Antonio F. / Álvarez-Cubero, María Jesús

    Science of the Total Environment. 2023 Nov., v. 898 p.165530-

    2023  

    Abstract: The development and progression of prostate cancer (PCa) depends on complex interactions between genetic, environmental and dietary factors that modulate the carcinogenesis process. Interactions between chemical exposures and genetic polymorphisms in ... ...

    Abstract The development and progression of prostate cancer (PCa) depends on complex interactions between genetic, environmental and dietary factors that modulate the carcinogenesis process. Interactions between chemical exposures and genetic polymorphisms in genes encoding xenobiotic metabolizing enzymes (XME), antioxidant enzymes and DNA repair enzymes have been reported as the main drivers of cancer. Thus, a better understanding of the causal risk factors for PCa will provide avenues to identify men at increased risk and will contribute to develop effective detection and prevention methods. We performed a meta-analysis on 17,518 cases and 42,507 controls obtained from 42 studies to determine whether seven SNPs and one CNV pertaining to oxidative stress, xenobiotic detoxification and DNA repair enzymes are associated with the risk of PCa (GPX1 (rs1050450), XRCC1 (rs25487), PON1 (rs662), SOD2 (rs4880), CAT (rs1001179), GSTP1 (rs1695) and CNV GSTM1). A significant increased risk of PCa was found for SOD2 (rs4880) ORGG₊GA ᵥₛ. AA 1.08; 95%CI 1.01–1.15, CAT (rs1001179) ORTT ᵥₛ. TC₊CC 1.39; 95%CI 1.17–1.66, PON1 (rs662) ORCT ᵥₛ. CC₊TT 1.17; 95%CI 1.01–1.35, GSTP1 (rs1695) ORGG ᵥₛ. GA₊AA 1.20; 95%CI 1.05–1.38 and GSTM1 (dual null vs. functional genotype) ORN ᵥₛ. NN₁₊NN₂ 1.34; 95%CI 1.10–1.64. The meta-analysis showed that the CNV GSTM1, and the SNPs GSTP1 (rs1695) and CAT (rs1001179) are strongly associated with a greater risk of PCa and, to a lesser extent, the genetic variants SOD2 (rs4880) and PON1 (rs662). Although several antioxidant enzymes and XME play an important role in the PCa development, other risk factors such as chemical exposures should also be considered to gain insight on PCa risk. The functional in silico analysis showed that the genetic variants studied had no clinical implication regarding malignancy, except for GPX1 (rs1050450) SNP.
    Keywords DNA repair ; antioxidants ; carcinogenesis ; computer simulation ; environment ; genotype ; meta-analysis ; oxidative stress ; prostatic neoplasms ; risk ; xenobiotics ; BPH ; CAT ; CNV ; CI ; EDTA ; ESR ; GPX ; GST ; HDL ; HWE ; n ; NAT ; NMD ; OR ; PCa ; PCR ; PON1 ; PRDX ; PSA ; ROS ; SNP ; SOD ; TNM ; TXNRD ; XME ; XRCC1 ; Antioxidant enzymes ; Xenobiotic metabolizing enzymes ; Genetic polymorphism ; Prostate cancer
    Language English
    Dates of publication 2023-11
    Publishing place Elsevier B.V.
    Document type Article ; Online
    ZDB-ID 121506-1
    ISSN 1879-1026 ; 0048-9697
    ISSN (online) 1879-1026
    ISSN 0048-9697
    DOI 10.1016/j.scitotenv.2023.165530
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

  6. Article ; Online: Combining microfluidics with machine learning algorithms for RBC classification in rare hereditary hemolytic anemia.

    Rizzuto, Valeria / Mencattini, Arianna / Álvarez-González, Begoña / Di Giuseppe, Davide / Martinelli, Eugenio / Beneitez-Pastor, David / Mañú-Pereira, Maria Del Mar / Lopez-Martinez, Maria José / Samitier, Josep

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 13553

    Abstract: Combining microfluidics technology with machine learning represents an innovative approach to conduct massive quantitative cell behavior study and implement smart decision-making systems in support of clinical diagnostics. The spleen plays a key-role in ... ...

    Abstract Combining microfluidics technology with machine learning represents an innovative approach to conduct massive quantitative cell behavior study and implement smart decision-making systems in support of clinical diagnostics. The spleen plays a key-role in rare hereditary hemolytic anemia (RHHA), being the organ responsible for the premature removal of defective red blood cells (RBCs). The goal is to adapt the physiological spleen filtering strategy for in vitro study and monitoring of blood diseases through RBCs shape analysis. Then, a microfluidic device mimicking the slits of the spleen red pulp area and video data analysis are combined for the characterization of RBCs in RHHA. This microfluidic unit is designed to evaluate RBC deformability by maintaining them fixed in planar orientation, allowing the visual inspection of RBC's capacity to restore their original shape after crossing microconstrictions. Then, two cooperative learning approaches are used for the analysis: the majority voting scheme, in which the most voted label for all the cell images is the class assigned to the entire video; and the maximum sum of scores to decide the maximally scored class to assign. The proposed platform shows the capability to discriminate healthy controls and patients with an average efficiency of 91%, but also to distinguish between RHHA subtypes, with an efficiency of 82%.
    MeSH term(s) Anemia, Hemolytic, Congenital/classification ; Anemia, Hemolytic, Congenital/pathology ; Erythrocyte Deformability ; Erythrocytes/classification ; Erythrocytes/pathology ; Female ; Humans ; Image Processing, Computer-Assisted ; Lab-On-A-Chip Devices ; Machine Learning ; Male ; Microfluidic Analytical Techniques
    Language English
    Publishing date 2021-06-30
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-92747-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: Cooperative cell motility during tandem locomotion of amoeboid cells.

    Bastounis, Effie / Álvarez-González, Begoña / del Álamo, Juan C / Lasheras, Juan C / Firtel, Richard A

    Molecular biology of the cell

    2016  Volume 27, Issue 8, Page(s) 1262–1271

    Abstract: Streams of migratory cells are initiated by the formation of tandem pairs of cells connected head to tail to which other cells subsequently adhere. The mechanisms regulating the transition from single to streaming cell migration remain elusive, although ... ...

    Abstract Streams of migratory cells are initiated by the formation of tandem pairs of cells connected head to tail to which other cells subsequently adhere. The mechanisms regulating the transition from single to streaming cell migration remain elusive, although several molecules have been suggested to be involved. In this work, we investigate the mechanics of the locomotion ofDictyosteliumtandem pairs by analyzing the spatiotemporal evolution of their traction adhesions (TAs). We find that in migrating wild-type tandem pairs, each cell exerts traction forces on stationary sites (∼80% of the time), and the trailing cell reuses the location of the TAs of the leading cell. Both leading and trailing cells form contractile dipoles and synchronize the formation of new frontal TAs with ∼54-s time delay. Cells not expressing the lectin discoidin I or moving on discoidin I-coated substrata form fewer tandems, but the trailing cell still reuses the locations of the TAs of the leading cell, suggesting that discoidin I is not responsible for a possible chemically driven synchronization process. The migration dynamics of the tandems indicate that their TAs' reuse results from the mechanical synchronization of the leading and trailing cells' protrusions and retractions (motility cycles) aided by the cell-cell adhesions.
    MeSH term(s) Biomechanical Phenomena ; Cell Adhesion ; Cell Adhesion Molecules/genetics ; Cell Adhesion Molecules/metabolism ; Cell Movement/physiology ; Dictyostelium/cytology ; Dictyostelium/genetics ; Discoidins/genetics ; Discoidins/metabolism
    Chemical Substances Cell Adhesion Molecules ; Discoidins
    Language English
    Publishing date 2016-04-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1098979-1
    ISSN 1939-4586 ; 1059-1524
    ISSN (online) 1939-4586
    ISSN 1059-1524
    DOI 10.1091/mbc.E15-12-0836
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Caso clínico: gammagrafía de sulfuro coloidal, herramienta diagnóstica para diferenciar entre infarto y osteomielitis en un paciente con anemia drepanocítica.

    Soto-Insuga, V / Alvarez González, B / Rubio Gribble, B / Ramos Amador, J T

    Anales de pediatria (Barcelona, Spain : 2003)

    2010  Volume 72, Issue 3, Page(s) 224–225

    Title translation Clinical case: sulphur colloid scintigraphy, a diagnostic tool to differentiate between an infarction and osteomyelitis in a patient with drepanocytic anaemia.
    MeSH term(s) Anemia, Sickle Cell/complications ; Bone and Bones/blood supply ; Child, Preschool ; Diagnosis, Differential ; Humans ; Infarction/diagnostic imaging ; Infarction/etiology ; Male ; Osteomyelitis/diagnostic imaging ; Osteomyelitis/etiology ; Radionuclide Imaging ; Radiopharmaceuticals ; Technetium Tc 99m Sulfur Colloid
    Chemical Substances Radiopharmaceuticals ; Technetium Tc 99m Sulfur Colloid (556Q0P6PB1)
    Language Spanish
    Publishing date 2010-03
    Publishing country Spain
    Document type Case Reports ; Letter
    ISSN 1695-9531
    ISSN (online) 1695-9531
    DOI 10.1016/j.anpedi.2009.11.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Two-Layer Elastographic 3-D Traction Force Microscopy.

    Álvarez-González, Begoña / Zhang, Shun / Gómez-González, Manuel / Meili, Ruedi / Firtel, Richard A / Lasheras, Juan C / Del Álamo, Juan C

    Scientific reports

    2017  Volume 7, Page(s) 39315

    Abstract: Cellular traction force microscopy (TFM) requires knowledge of the mechanical properties of the substratum where the cells adhere to calculate cell-generated forces from measurements of substratum deformation. Polymer-based hydrogels are broadly used for ...

    Abstract Cellular traction force microscopy (TFM) requires knowledge of the mechanical properties of the substratum where the cells adhere to calculate cell-generated forces from measurements of substratum deformation. Polymer-based hydrogels are broadly used for TFM due to their linearly elastic behavior in the range of measured deformations. However, the calculated stresses, particularly their spatial patterns, can be highly sensitive to the substratum's Poisson's ratio. We present two-layer elastographic TFM (2LETFM), a method that allows for simultaneously measuring the Poisson's ratio of the substratum while also determining the cell-generated forces. The new method exploits the analytical solution of the elastostatic equation and deformation measurements from two layers of the substratum. We perform an in silico analysis of 2LETFM concluding that this technique is robust with respect to TFM experimental parameters, and remains accurate even for noisy measurement data. We also provide experimental proof of principle of 2LETFM by simultaneously measuring the stresses exerted by migrating Physarum amoeboae on the surface of polyacrylamide substrata, and the Poisson's ratio of the substrata. The 2LETFM method could be generalized to concurrently determine the mechanical properties and cell-generated forces in more physiologically relevant extracellular environments, opening new possibilities to study cell-matrix interactions.
    MeSH term(s) Imaging, Three-Dimensional/methods ; Microscopy, Atomic Force/methods ; Physarum/cytology ; Traction
    Language English
    Publishing date 2017-01-11
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep39315
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article ; Online: Three-dimensional balance of cortical tension and axial contractility enables fast amoeboid migration.

    Álvarez-González, Begoña / Meili, Ruedi / Bastounis, Effie / Firtel, Richard A / Lasheras, Juan C / Del Álamo, Juan C

    Biophysical journal

    2015  Volume 108, Issue 4, Page(s) 821–832

    Abstract: Fast amoeboid migration requires cells to apply mechanical forces on their surroundings via transient adhesions. However, the role these forces play in controlling cell migration speed remains largely unknown. We used three-dimensional force microscopy ... ...

    Abstract Fast amoeboid migration requires cells to apply mechanical forces on their surroundings via transient adhesions. However, the role these forces play in controlling cell migration speed remains largely unknown. We used three-dimensional force microscopy to measure the three-dimensional forces exerted by chemotaxing Dictyostelium cells, and examined wild-type cells as well as mutants with defects in contractility, internal F-actin crosslinking, and cortical integrity. We showed that cells pull on their substrate adhesions using two distinct, yet interconnected mechanisms: axial actomyosin contractility and cortical tension. We found that the migration speed increases when axial contractility overcomes cortical tension to produce the cell shape changes needed for locomotion. We demonstrated that the three-dimensional pulling forces generated by both mechanisms are internally balanced by an increase in cytoplasmic pressure that allows cells to push on their substrate without adhering to it, and which may be relevant for amoeboid migration in complex three-dimensional environments.
    MeSH term(s) Actins/metabolism ; Actomyosin/metabolism ; Chemotaxis ; Cytoplasm/metabolism ; Dictyostelium/metabolism ; Dictyostelium/physiology
    Chemical Substances Actins ; Actomyosin (9013-26-7)
    Language English
    Publishing date 2015-02-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2014.11.3478
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top