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Triple-negative breast cancer (TNBC) is particularly challenging due to the weak or absent response to therapeutics and its poor prognosis. The effectiveness of neoadjuvant chemotherapy (NAC) response is strongly influenced by changes in elements of the tumor microenvironment (TME). This work aimed to characterize the residual TME composition in 96 TNBC patients using immunohistochemistry and in situ hybridization techniques and evaluate its prognostic implications for partial responders vs. non-responders. Compared with non-responders, partial responders containing higher levels of CD83+ mature dendritic cells, FOXP3+ regulatory T cells, and IL-15 expression but lower CD138+ cell concentration exhibited better OS and RFS. However, along with tumor diameter and positive nodal status at diagnosis, matrix metalloproteinase-9 (MMP-9) expression in the residual TME was identified as an independent factor associated with the impaired response to NAC. This study yields new insights into the key components of the residual tumor bed, such as MMP-9, which is strictly associated with the lack of a pathological response to NAC. This knowledge might help early identification of TNBC patients less likely to respond to NAC and allow the establishment of new therapeutic targets.

With a high risk of relapse and death, and a poor or absent response to therapeutics, the triple-negative breast cancer (TNBC) subtype is particularly challenging, especially in patients who cannot achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Although the tumor microenvironment (TME) is known to influence disease progression and the effectiveness of therapeutics, its predictive and prognostic potential remains uncertain. This work aimed to define the residual TME profile after NAC of a retrospective cohort with 96 TNBC patients by immunohistochemical staining (cell markers) and chromogenic in situ hybridization (genetic markers). Kaplan–Meier curves were used to estimate the influence of the selected TME markers on five-year overall survival (OS) and relapse-free survival (RFS) probabilities. The risks of each variable being associated with relapse and death were determined through univariate and multivariate Cox analyses. We describe a unique tumor-infiltrating immune profile with high levels of lymphocytes (CD4, FOXP3) and dendritic cells (CD21, CD1a and CD83) that are valuable prognostic factors in post-NAC TNBC patients. Our study also demonstrates the value of considering not only cellular but also genetic TME markers such as MUC-1 and CXCL13 in routine clinical diagnosis to refine prognosis modelling.

The Personal Style of the Therapist (PST) is a multidimensional construction that is present in every therapeutic process. Aim. This research studies the differences between Italian and Chilean post-rationalist cognitive therapists. Method. A cross-sectional analysis was conducted to compare therapists in the five dimensions of EPT. For this purpose, a t-test was applied. The EPT-C questionnaire was administered to a total sample of 63 post-rational cognitive therapists of both nationalities. Results. The results revealed statistically significant differences in expressive function (p =,004). Italian therapists showed the highest values. Conclusion. In the five functions evaluated by ETP only significant differences for expressive function were found., El estilo personal del terapeuta (PST) es una construcción multidimensional que está presente en cada proceso terapéutico. Objetivo. Esta investigación estudia las diferencias entre los terapeutas cognitivos posracionalistas italianos y chilenos. Método. Se realizó un análisis transversal para comparar terapeutas en las cinco dimensiones de EPT. Para este propósito, se aplicó una prueba t. El cuestionario EPT-C se administró a una muestra total de 63 terapeutas cognitivos posracionales de ambas nacionalidades. Resultados Los resultados revelaron diferencias estadísticamente significativas en la función expresiva (p =, 004). Los terapeutas italianos mostraron los valores más altos. Conclusión. En las cinco funciones evaluadas por ETP solo se encontraron diferencias significativas para la función expresiva.

El estilo personal del terapeuta (EPT) es un constructo multidimensional que se presenta en todo proceso terapéutico. El objetivo de la presente revisión bibliográfica fue revisar el estado del arte en la investigación sobre el estilo personal del terapeuta en psicoterapeutas cognitivo post-racionalistas. Se encontraron 2 publicaciones en revistas WoS. Además, se incluyó una investigación en proceso., The Personal Style of the Therapist (PST) is a multidimensional construction that is present in every therapeutic process. The aim of this literature review was to review the state of the art in research on the personal style of the therapist in post-rationalist cognitive psychotherapists. We found 2 publications in WoS journals. In addition, an ongoing investigation was included.

This monographic of the revista de psicoterapia entitled "Cognitive Pychotherapy Post-Rationalist: Openings" is about the Guidanist Tradition on the eve of entering the third decade of the 21st century, El presente número monográfico de la revista de psicoterapia titulado “Terapia Cognitiva Post-Racionalista: Aperturas” trata sobre la tradición Guidanista en vísperas de entrar a la tercera década del siglo XXI.

Introduction: Delta-like ligand 4 (DLL4) is a ligand that activates the Notch pathway, which is important for cancer stem cell (CSC) survival. Demcizumab is a humanized, anti- DLL4 antibody that has been shown using an in vivo tumorigenicity limiting dilution assay to inhibit tumor growth and decrease CSC frequency in minimally passaged human xenograft models. In addition, inhibition of DLL4 has also been shown in preclinical studies to cause dysfunctional sprouting of new vessels, resulting in an antiangiogenic effect. Data from a phase 1b study of carboplatin (C), pemetrexed (P), and demcizumab (D) in patients with 1 -line metastatic non-squamous NSCLC led to this double-blind randomized 3-arm placebo (Pl)-controlled phase 2 study. Method(s): Patients with non-squamous NSCLC were randomized (1:1:1) to 1 -line therapy with either Arm 1 -CPPl, Arm 2 -CPD with a single 70-day truncated course of demcizumab or Arm 3 - CPD with two 70-day truncated courses of demcizumab (second course starting on Day 168). CP were given at usual dose and schedule; P/D was given IV on days 1 and 15 in cycles 1-3 and 7-9. The primary endpoint was response rate and secondary endpoints included progression-free survival, survival, safety, immunogenicity, pharmacokinetics, and biomarkers of Notch signaling and CSCs in blood, hair follicles, and tumor cells. The primary study analyses compared CPPl to the two pooled CPD arms. Result(s): 82 patients were randomized and all 82 were treated. The median age was 61, the male/female ratio was 40/42, 80 pts had adenocarcinoma, 0 pts harbored EGFR mutation or ALK rearrangement, and 15 were KRAS mutated. The response/clinical benefit rates were 52%/92% and 28%/79% in the CPPl and pooled CPD arms, respectively (response p value = 0.04). The median progression-free survival (PFS) was 8.7 months (95% CI: 5.4-12.5) in the CPPl arm and 5.5 months (95% CI: 4.1-6.9) in the pooled CPD arms (HR = 2.3; 95%CI: 1.1-4.8). The interim median overall survival (OS)

Introduction: Delta-like ligand 4 (DLL4) is a ligand that activates the Notch pathway, which is important for cancer stem cell (CSC) survival. Demcizumab is a humanized, anti- DLL4 antibody that has been shown using an in vivo tumorigenicity limiting dilution assay to inhibit tumor growth and decrease CSC frequency in minimally passaged human xenograft models. In addition, inhibition of DLL4 has also been shown in preclinical studies to cause dysfunctional sprouting of new vessels, resulting in an antiangiogenic effect. Data from a phase 1b study of carboplatin (C), pemetrexed (P), and demcizumab (D) in patients with 1 -line metastatic non-squamous NSCLC led to this double-blind randomized 3-arm placebo (Pl)-controlled phase 2 study. Method(s): Patients with non-squamous NSCLC were randomized (1:1:1) to 1 -line therapy with either Arm 1 -CPPl, Arm 2 -CPD with a single 70-day truncated course of demcizumab or Arm 3 - CPD with two 70-day truncated courses of demcizumab (second course starting on Day 168). CP were given at usual dose and schedule; P/D was given IV on days 1 and 15 in cycles 1-3 and 7-9. The primary endpoint was response rate and secondary endpoints included progression-free survival, survival, safety, immunogenicity, pharmacokinetics, and biomarkers of Notch signaling and CSCs in blood, hair follicles, and tumor cells. The primary study analyses compared CPPl to the two pooled CPD arms. Result(s): 82 patients were randomized and all 82 were treated. The median age was 61, the male/female ratio was 40/42, 80 pts had adenocarcinoma, 0 pts harbored EGFR mutation or ALK rearrangement, and 15 were KRAS mutated. The response/clinical benefit rates were 52%/92% and 28%/79% in the CPPl and pooled CPD arms, respectively (response p value = 0.04). The median progression-free survival (PFS) was 8.7 months (95% CI: 5.4-12.5) in the CPPl arm and 5.5 months (95% CI: 4.1-6.9) in the pooled CPD arms (HR = 2.3; 95%CI: 1.1-4.8). The interim median overall survival (OS)

The Juan Fernández and Desventuradas islands are among the few oceanic islands belonging to Chile. They possess a unique mix of tropical, subtropical, and temperate marine species, and although close to continental South America, elements of the biota have greater affinities with the central and south Pacific owing to the Humboldt Current, which creates a strong biogeographic barrier between these islands and the continent. The Juan Fernández Archipelago has ~ 700 people, with the major industry being the fishery for the endemic lobster, Jasus frontalis. The Desventuradas Islands are uninhabited except for a small Chilean military garrison on San Félix Island. We compared the marine biodiversity of these islands across multiple taxonomic groups. At San Ambrosio Island (SA), in Desventuradas, the laminarian kelp (Eisenia cokeri), which is limited to Desventuradas in Chile, accounted for >50% of the benthic cover at wave exposed areas, while more sheltered sites were dominated by sea urchin barrens. The benthos at Robinson Crusoe Island (RC), in the Juan Fernández Archipelago, comprised a diverse mix of macroalgae and invertebrates, a number of which are endemic to the region. The biomass of commercially targeted fishes was > 2 times higher in remote sites around RC compared to sheltered locations closest to port, and overall biomass was 35% higher around SA compared to RC, likely reflecting fishing effects around RC. The number of endemic fish species was extremely high at both islands, with 87.5% of the species surveyed at RC and 72% at SA consisting of regional endemics. Remarkably, endemics accounted for 99% of the numerical abundance of fishes surveyed at RC and 96% at SA, which is the highest assemblage-level endemism known for any individual marine ecosystem on earth. Our results highlight the uniqueness and global significance of these biodiversity hotspots exposed to very different fishing pressures.

Due to the ever-increasing use of the coastline for industrial purposes, particularly by those activities that take up great amounts of sea water, it is fundamental to understand the composition of the planktonic fauna and its natural spatial and temporal variability in relation to hydrographic variables, in order to understand the potential impact of such undertakings. Totoralillo Norte (~30°S) is an embayment located within a well-known area of recurring upwelling events, as well as a zone with projection for industrial development. Here we performed seasonal surveys (several days sampling within each season) during 2013 and 2014 recognizing an abundant zooplanktonic community with a good representation of the main taxa comprised by at least 166 species. In terms of numbers, copepods dominated the holoplankton (91.7%), whereas meroplankton was mainly composed of larval stages of barnacles, mollusks, decapods, bryozoans and fish. In spite this being a coastal zone normally affected by upwelling events, zooplankton abundance was high throughout the year, even during periods dominated by weak winds and downwelling conditions. Studies such as this can help unveil relevant ecological patterns and their related processes; vital information that must be considered during an environmental impact assessments., Debido al creciente uso del borde costero con fines industriales, particularmente aquellas actividades que utilizan cantidades importantes de agua de mar, es fundamental entender la composición de la fauna planctónica junto con reconocer su variabilidad espacial y temporal en función de variables hidrográficas relevantes. Totoralillo Norte (~30°S) es un bahía localizada dentro de un área comúnmente afectada por eventos de surgencia, así como una zona que se proyecta relevante para el desarrollo industrial. Aquí se realizaron muestreos estacionales (varios días en cada estación) durante 2013 y 2014 donde se pudo reconocer una comunidad zooplanctónica abundante con una buena representación de los principales taxa, conformada por al menos 166 especies. Los copépodos dominaron en términos numéricos el holoplancton (91,7%), mientras que el meroplancton estuvo compuesto principalmente por estadios larvales de cirripedios, moluscos, decápodos, briozoos y peces. A pesar de ser una zona de la costa normalmente afectada por eventos de surgencia, la abundancia del zooplancton fue elevada durante todo el año, incluso durante períodos dominados por vientos débiles y condiciones de hundimiento. Estudios como este ayudan a develar patrones ecológicos relevantes así como procesos que los afectan; información vital y que debe ser considerada al momento de evaluar impactos ambientales.

The Juan Fernández and Desventuradas islands are among the few oceanic islands belonging to Chile. They possess a unique mix of tropical, subtropical, and temperate marine species, and although close to continental South America, elements of the biota have greater affinities with the central and south Pacific owing to the Humboldt Current, which creates a strong biogeographic barrier between these islands and the continent. The Juan Fernández Archipelago has ~700 people, with the major industry being the fishery for the endemic lobster, Jasus frontalis. The Desventuradas Islands are uninhabited except for a small Chilean military garrison on San Félix Island. We compared the marine biodiversity of these islands across multiple taxonomic groups. At San Ambrosio Island (SA), in Desventuradas, the laminarian kelp (Eisenia cokeri), which is limited to Desventuradas in Chile, accounted for >50% of the benthic cover at wave exposed areas, while more sheltered sites were dominated by sea urchin barrens. The benthos at Robinson Crusoe Island (RC), in the Juan Fernández Archipelago, comprised a diverse mix of macroalgae and invertebrates, a number of which are endemic to the region. The biomass of commercially targeted fishes was >2 times higher in remote sites around RC compared to sheltered locations closest to port, and overall biomass was 35% higher around SA compared to RC, likely reflecting fishing effects around RC. The number of endemic fish species was extremely high at both islands, with 87.5% of the species surveyed at RC and 72% at SA consisting of regional endemics. Remarkably, endemics accounted for 99% of the numerical abundance of fishes surveyed at RC and 96% at SA, which is the highest assemblage-level endemism known for any individual marine ecosystem on earth. Our results highlight the uniqueness and global significance of these biodiversity hotspots exposed to very different fishing pressures.

Many herbivores specialize on a specific type of host that can serve both as food and shelter. Such associations, however, do not necessarily last throughout the ontogeny of the herbivore. For example, in field surveys a close association between the herbivorous crab Taliepus dentatus and brown algae has been found. However, newly settled and juvenile individuals were only found on patches of the brown algae Glossophora kunthii, while older individuals of the population were most frequently found living on the common brown kelp Lessonia trabeculata. Our field and laboratory experiments showed that different size classes of this crab species may actively select these algal habitats, and that these preferences are even more conspicuous for small newly settled individuals. Bioassay experiments showed that fish specifically avoided either T. dentatus or G. kunthii, which suggests that consumption of this alga by T. dentatus could decrease their natural rates of mortality due to fish predation. These results were further corroborated through field tethering experiments, where individuals of this species exhibited high survivorship regardless of the surrounding substrate on which they were placed. In this study, we speculate that incorporation of anti-predator defenses from algae may then enhance the survivorship of juveniles, thus, deterring consumers like carnivorous fish common in these environments. Although less threatened, because they are too large to be consumed by predatory fish, older individuals might also benefit from living on L. trabeculata, which is rich in secondary metabolites., La mayoría de los herbívoros se especializan en tipos específicos de huéspedes que les sirven como refugios y alimento. Tales asociaciones, sin embargo, no necesariamente perduran a lo largo de su ontogenia. Por ejemplo, en observaciones de terreno se ha encontrado una fuerte asociación entre la jaiba herbívora Taliepus dentatus y las algas pardas. Sin embargo, individuos recién asentados y juveniles se encuentran sólo en parches del alga parda Glossophora kunthii, mientras que los individuos adultos de la población se encuentran más frecuentemente asociados al huiro submareal Lessonia trabeculata. Nuestros experimentos de terreno y laboratorio mostraron que distintas clases de tamaño de esta especie de jaiba podrían seleccionar activamente estas especies de algas siendo estas preferencias más conspicuas en individuos recién asentados. Experimentos de bioensayos mostraron que los peces evitan a T. dentatus o G. kunthii, lo cual sugiere que el consumo de esta alga por T. dentatus podría disminuir sus tasas de mortalidad natural debido a la depredación por peces. Estos resultados se corroboraron además mediante experimentos de amarre en terreno, donde individuos de esta especie exhibieron una alta sobrevivencia independiente del sustrato del enterno donde fueron expuestas. En este estudio se especula que la incorporación de defensas anti-depredatorias de algas podrian aumentar la sobrevivencia de juveniles, disuayendo así a consumidores como peces carnívoros comunes en estos ambientes. Aunque menos amenazados, porque son muy grandes para ser consumidos por peces carnívoros, los individuos adultos también podrían beneficiarse viviendo en el alga L. trabeculata, la cual es rica en metabolitos secundarios.

La circulación asociada a surgencias costeras tiene un efecto regional sobre la comunidad fitoplanctónica (i.e. aumento de las tasas fotosintéticas, incremento en biomasa), pero su influencia a escalas espaciales locales es menos clara. A una escala local (cientos de metros) y bajo condiciones de surgencia, zonas de retención con altos niveles de producción primaria (PP) tienden a ocurrir en el lado protegido de pequeñas penínsulas inducidas por la orientación, geometría, tamaño y geomorfología general de este tipo de formaciones costeras. Nosotros cuantificamos producción primaria neta (NPP), bruta (GPP), respiración comunitaria (CR) y biomasa (Chl-a) de ensambles naturales de fitoplancton en ambientes costeros de Chile central. El principal objetivo fue determinar un patrón a corto plazo en PP y CR en ambos lados de dos pequeñas penínsulas en Chile central, donde son esperables diferencias mensurables en varias variables ambientales. Nuestra hipótesis de trabajo es que estas diferencias no ocurren bajo condiciones de relajación o de no-surgencia. Los resultados indican que NPP, GPP y CR difieren a una escala local y, contrariamente a lo reportado previamente, encontramos que el debilitamiento de los vientos favorables a las surgencias pueden generar un patrón opuesto a lo observado durante un periodo activo de surgencia, donde el sitio expuesto retiene altas concentraciones de biomasa y exhibe elevados niveles de PP comparados con el sitio protegido. Nuestros resultados destacan la importancia de la variabilidad a corto plazo de PP y CR y su acople con la distribución y abundancia del fitoplancton y su rápida respuesta a una escala espacial local

The mutation of the p53 gene is a common phenomenon in numerous human tumors, leading to the accumulation of nonfunctioning p53 protein in the cell nucleus, which can be detected by immunohistochemistry. In breast cancer, it has been suggested that the overexpression of p53 protein in the nucleus is an indicator of poor prognosis, which must be borne in mind in selecting coadjuvant treatment for each patient. This study is an immunohistochemical analysis of p53 expression in 153 cases of mammary carcinoma, correlating it with histological grade, axillary node status, hormone receptors, cell-proliferation fraction and expression of the c-erbB-2 oncoprotein. Of all the breast-cancer tissue analyzed, 43.79% was positive for p53. The overexpression of this protein bears a direct statistically significant relationship to histological grade, cell-proliferation fraction and c-erbB-2, and an inverse relationship to estrogen and progesterone receptors. No statistically significant relationship was found with axillary node status. The expression of p53 in poorly differentiated tumors-commonly receptor negative and with a high proliferation fraction-may indicate greater tumor aggressiveness and a high risk of relapse.