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"documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2015;145:319-20" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 5 "HTML" => 5 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Serum tumour markers in asymptomatic patients" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "319" "paginaFinal" => "320" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Marcadores tumorales séricos en pacientes asintomáticos" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Joaquim Torné Cachot, José Manuel Baucells Azcona, Jesús Blanch Falp, David Blancas Altabella" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Joaquim" "apellidos" => "Torné Cachot" ] 1 => array:2 [ "nombre" => "José Manuel" "apellidos" => "Baucells Azcona" ] 2 => array:2 [ "nombre" => "Jesús" "apellidos" => "Blanch Falp" ] 3 => array:2 [ "nombre" => "David" "apellidos" => "Blancas Altabella" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775315001876" "doi" => "10.1016/j.medcli.2015.03.008" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775315001876?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616001054?idApp=UINPBA00004N" "url" => "/23870206/0000014500000007/v2_201604010141/S2387020616001054/v2_201604010141/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2387020616000917" "issn" => "23870206" "doi" => "10.1016/j.medcle.2016.02.026" "estado" => "S300" "fechaPublicacion" => "2015-10-05" "aid" => "3261" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2015;145:317-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 5 "HTML" => 5 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Ocular thelaziosis, an emergent zoonosis in Spain" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "317" "paginaFinal" => "318" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Thelaziosis ocular, una zoonosis emergente en España" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1735 "Ancho" => 1625 "Tamanyo" => 247003 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Specimen of <span class="elsevierStyleItalic">Thelazia callipaeda</span> collected from the conjunctival sac of the patient.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ramiro López Medrano, Gloria Guerra Calleja, Carolina Díez Morrondo, Rosario Panadero Fontán" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Ramiro" "apellidos" => "López Medrano" ] 1 => array:2 [ "nombre" => "Gloria" "apellidos" => "Guerra Calleja" ] 2 => array:2 [ "nombre" => "Carolina" "apellidos" => "Díez Morrondo" ] 3 => array:2 [ "nombre" => "Rosario" "apellidos" => "Panadero Fontán" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775315001323" "doi" => "10.1016/j.medcli.2015.02.014" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775315001323?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616000917?idApp=UINPBA00004N" "url" => "/23870206/0000014500000007/v2_201604010141/S2387020616000917/v2_201604010141/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Concurrent lymphoid and Philadelphia chromosome-negative myeloproliferative neoplasms" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">Dear Editor</span>," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "318" "paginaFinal" => "319" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Jose Miguel Torregrosa, Gloria Soler, Shirley Cancio, Francisca Ferrer-Marin" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Jose Miguel" "apellidos" => "Torregrosa" ] 1 => array:2 [ "nombre" => "Gloria" "apellidos" => "Soler" ] 2 => array:2 [ "nombre" => "Shirley" "apellidos" => "Cancio" ] 3 => array:4 [ "nombre" => "Francisca" "apellidos" => "Ferrer-Marin" "email" => array:1 [ 0 => "fferrermarin@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Unidad de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Instituto Murciano de Investigación Biosanitaria, Murcia, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neoplasias mieloproliferativas crónicas con cromosoma Filadelfia negativo y neoplasias linfoides concurrentes" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Three studies have shown that patients with chronic myeloproliferative neoplasms (cMPN) have 2.8–3.4 times higher risk of developing a lymphoproliferative neoplasim (LPN) compared to general population.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–3</span></a> In most cases, the diagnosis of LPN is subsequent to cMPN, and in less than 10% cases it is synchronous or prior to the development of myeloid disease, possibly by the increased aggressiveness of lymphoid neoplasms. Therefore, these patients would die before developing a cMPN. The molecular basis underlying this association is not well understood. In recent years, in addition to <span class="elsevierStyleItalic">JAK2</span><span class="elsevierStyleSup">V617F</span>, in cMPN patients, an increasing number of mutations have been identified in other genes, such as: <span class="elsevierStyleItalic">DNMT3A</span>, <span class="elsevierStyleItalic">TET2</span>, <span class="elsevierStyleItalic">ASXL1</span>, <span class="elsevierStyleItalic">NRAS/KRAS</span>, <span class="elsevierStyleItalic">TP53</span>, <span class="elsevierStyleItalic">AML1/RUNX1</span>, <span class="elsevierStyleItalic">CBL</span>, <span class="elsevierStyleItalic">CALR</span>.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5</span></a> Defects in some of these genes have also been identified in patients with lymphoid neoplasms.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,6,7</span></a> In fact, recent studies have shown that epigenetic changes might have a role in lymphogenesis.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In this study, the prevalence and timing of LPN was assessed in patients diagnosed with cMPN (according to the World Health Organization criteria at the time of reporting data<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a>) recorded in our database from 2000 to 2013. In patients with both diseases it was studied whether mutations in genes related to myeloid condition lead to this association. In genomic DNA obtained from whole blood after venipuncture at diagnosis, the presence of the JAK2<span class="elsevierStyleSup">V617F</span> mutation was analyzed in all patients; c-KIT<span class="elsevierStyleSup">D816V</span> in patients with suspected systemic mastocytosis (SM) (both by polymerase chain reaction [PCR], quantitative in real-time); CALR in JAK2<span class="elsevierStyleSup">V617F</span>-negative patients (by analysis of PCR fragments),<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> and in patients with both neoplasms (cMPN and LPN), a selected panel of genes (CBL [exons 8 and 9], ASXL1 [exon 12], NRAS/KRAS [exons 1 and 2], IDH1/2 [exon 4] and the complete coding region of TET2 and RUNX1) by Sanger-type sequencing.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The overall study included 216 patients (122 cases of essential thrombocythemia [ET], 50 of polycythemia vera [PV], 38 of myelofibrosis and 6 SM), with a median age at diagnosis of 49 years (IQR 22–92) and a median follow-up of 82 months (IQR 42–132). Of the 216 cMPN patients included, 4 (1.85%) had a concurrent LPN. Clinical and biological characteristics of these 4 patients are reported in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The lymphoid neoplasms identified were two chronic lymphatic leukemia (CLL, cases 1 and 2), 1 Primary cutaneous centrofollicular non-Hodgkin lymphoma (case 3) and a T-cell large granular lymphocyte leukemia(T-LGL) (case 4). Unlike other studies,<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> in ours, LPN diagnosis was prior to (case 3), or synchronous to the cMPN (remaining cases) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). One patient (case 3) required specific treatment for lymphoid neoplasm (R-CHOP chemotherapy plus local radiation therapy), while the rest remain in therapeutic abstention regarding this disease. Regarding the mutational status of the 3 cMPN patients with negative Philadelphia chromosome (1 PV and 2 ET) JAK2 was mutated in 2 of them. In the third patient, negative for JAK2<span class="elsevierStyleSup">V617F</span>, mutations in CALR (case 1) were not found either. The SM patient presented mutation in c-KIT<span class="elsevierStyleSup">D816V</span>. However, none of the 4 patients with concurrent cMPN and LPN showed mutations in the panel of selected genes (KRAS, NRAS, CBL, ASXL1, IDH1/2, TP53, RUNX1 and TET2).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Association between cMPN and LPN is a rare event: ∼1–1.34% incidence.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–3</span></a> According to the medical literature,<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> in our study, the incidence of this association is higher in men, and CLL is the LPN most frequently associated. We describe the second case ever reported on the association between a cMPN and T-LGL<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> and the first in which the association is with a primary cutaneous lymphoma. The latter patient also developed, while under cytoreductive therapy with hydroxyurea, a prostate neoplasm and a colon neoplasm. Although it has been suggested that hydroxyurea can induce mutations in TP53,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> one of the genes most frequently mutated in human cancers, no mutations were reported in this gene.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Also it is interesting in our study the association between SM with a B-CLL. The SM associated to clonal hematological disease of line other than mast cell, account for 30% of SM, but are frequently associated with myeloid neoplasms, mainly chronic myelomonocytic leukemia.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> The association with lymphoid neoplasm, as in our case, is unusual.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In summary, previous studies have attempted to address the question of whether there is a genetic predisposition to both hematological diseases (cMPN-LPN), with poor results.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> In our study, we have not detected additional mutations other than c-KIT<span class="elsevierStyleSup">D816V</span> and JAK2<span class="elsevierStyleSup">V617F</span>, previously known. The small size of our sample, along with the low frequency of these mutations in cMPN,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> is the main limitation of this study. Despite these results, we cannot rule out that genes other than the selected genes (such as DNMT3A, SF3B1, NOTCH), or even not discovered yet, might promote genetic predisposition to both hematological neoplasms.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Torregrosa JM, Soler G, Cancio S, Ferrer-Marin F. Neoplasias mieloproliferativas crónicas con cromosoma Filadelfia negativo y neoplasias linfoides concurrentes. Med Clin (Barc). 2015;145:318–319.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">CLL, chronic lymphocytic leukemia; NHL, non-Hodgkin lymphoma; SM, systemic mastocytosis; LPN, lymphoproliferative neoplasm; CMPN, chronic myeloproliferative neoplasia; PV, polycythemia vera; RT, radiotherapy; M, male.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Case \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Sex \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">cMPN \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Age at diagnosis</th><th class="td" title="table-head " align="left" valign="top" scope="col">LPN \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Mutation \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Cytogenetics \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Accompanying solid tumors (stage, treatment) \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">cMPN \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LPN \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B-CLL (Rai-Binet 0-A) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">JAK2</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">V617F</span></span> non mutated. <span class="elsevierStyleItalic">CALR</span> non mutated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B-CLL (Rai-Binet 0-A) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">c-<span class="elsevierStyleItalic">KIT</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">D816V</span></span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Trisomy 12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary cutaneous follicular NHL (stage 3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">JAK2</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">V617F</span></span> mutated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prostate neoplasm (in situ, local RT) Rectal adenocarcinoma (B Coller, surgery) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T-cell large granular lymphocyte leukemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">JAK2</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">V617F</span></span> mutated \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not available \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1024707.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Characteristics of patients diagnosed with chronic myeloproliferative neoplasm and lymphoproliferative neoplasm.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased 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