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La cordillera de los Andes es la cadena montañosa más larga del mundo, influye directamente en el territorio en aspectos como el clima, las comunicaciones o las relaciones sociales, y ha sido representada en múltiples ocasiones en producciones audiovisuales. En el artículo se indaga el papel que tiene la geografía en el desarrollo de las narraciones cinematográficas que tienen como marco la cordillera de los Andes, al dar a conocer imaginarios geográficos que se proyectan a través del cine. La investigación es de naturaleza analítico-descriptiva, con una metodología cuantitativa y la utilización de la técnica de la observación científica. Se seleccionaron un total de veintiún filmaciones en las que los Andes son protagonistas, y se analizaron los fenómenos geográficos existentes en este espacio geográfico. Los resultados muestran la existencia de numerosos rodajes en los que la trama se desarrolla en los Andes y el espectador puede contemplar fenómenos geográficos tanto físicos (el cambio climático o los conflictos ambientales) como humanos (las actividades económicas o el urbanismo). La relevancia de este estudio recae en que hasta la fecha no se ha realizado ninguna pesquisa acerca de la geografía de la cordillera vista a través del cine. Asimismo, este trabajo puede abrir nuevas investigaciones semejantes para otros espacios geográficos.

Este trabajo estudia la relación existente entre la forma jurídica de una empresa y el tamaño con el grado de consecución de los ODS sociales. Para ello, se ha trabajado con una muestra aleatoria de 351 empresas situadas en la Comunidad Valenciana (España). Los resultados indican que la forma jurídica no es determinante del grado de implantación de los ODS sociales; sin embargo, sí lo es el tamaño, pues son las pymes las que mayores dificultades tienen para la incorporación de estos ODS. Los hallazgos permiten orientar a la Administración Pública en la implementación de políticas y ayudas focalizadas en este tipo de empresas, para que estas puedan cumplir con los retos que marca la Agenda 2030.

Abstract Recommendations regarding the best time to start treatment in patients with relapsed/refractory multiple myeloma (RRMM) after biological relapse/progression (BR) are unclear. This observational, prospective, multicenter registry aimed to evaluate the impact on time to progression (TTP) of treatment initiation at BR versus at symptomatic clinical relapse (ClinR) based on the Spanish routine practice in adult patients with RRMM. Patients had two or less previous treatment lines and at least one previous partial response. Baseline characteristics and treatment outcomes were recorded, and survival was analyzed. Of 225 patients, 110 were treated at BR (TxBR group) and 115 at ClinR (TxClinR group) according to the investigators' criteria. The proportion of patients with higher ECOG, previous noncomplete remission (CR), and second relapse were significantly higher in the TxBR group compared to the TxClinR group. TheTxClinR group showed improved outcomes, including TTP, compared to the TxBR group. Progression‐free survival increased in the TxClinR group (56.2 months) compared to the TxBR group (32.5 months) (p = 0.0137), and median overall survival also increased (p = 0.0897). Median TTP was significantly longer in patients relapsing from a CR (50.4 months) and in their first relapse (38.7 months) compared to those relapsing from a non‐CR response (32.9 months) and in their second relapse (25.2 months). Physicians seemed to start treatment earlier in RRMM patients with poor prognosis features. Previous responses to anti‐MM treatment and the number of prior treatment lines were identified as prognosis factors, whereby relapse from CR and first relapse were associated with a longer time to progression.

Uno de los mayores desafíos a los que se enfrenta hoy día la población juvenil es a la desmotivación por los resultados académicos, lo que se ve estrechamente reflejado en conductas de estrés, ansiedad y depresión. Así, entre los trastornos más destacados en la población adolescente, se encuentra el Trastorno de Ansiedad Generalizada. Asistir a la escuela favorece el desarrollo integral de los estudiantes (académico, personal y social), no obstante, el índice de rechazo escolar continúa siendo alarmante. Debido a la complejidad del comportamiento, no se ha logrado llegar a un acuerdo común que justifique la conducta, pues las razones son heterogéneas (miedo, ansiedad o trastorno desafiante). La evitación escolar basada en las emociones es una importante causa de absentismo escolar, además de persistente. Teniendo en cuenta por tanto la estrecha relación entre las emociones de tipo internalizante (ansiedad, depresión, estrés) y el rechazo escolar, el objetivo del presente estudio consistió en conocer la relación entre la ansiedad escolar y el rechazo escolar en función de las altas y bajas puntuaciones en rechazo escolar. La muestra estuvo compuesta por un total de 1920 estudiantes de bachillerato. La School Refusal Behavior Assessment Scale-Revised for children (I. Evitación de afectividad negativa; II. Escape de situaciones sociales; III. Búsqueda de atención; IV. Búsqueda del refuerzo tangible) y el Inventario de Ansiedad Escolar (IAES) fueron utilizados. Los resultados reflejaron que, los estudiantes con altas puntuaciones en rechazo escolar, obtuvieron puntuaciones superiores en las diferentes dimensiones de ansiedad evaluadas en comparación con el grupo con bajas puntuaciones en rechazo escolar. Se discute el papel de la ansiedad como factor de riesgo del comportamiento de rechazo escolar.

School refusal has important repercussions on the lives of children and adolescents, seriously affecting their personal, academic, and social adjustment. Negative attitudes towards school can be caused simultaneously for several reasons and, due to the existing heterogeneity, Kearney, and Silverman (1990) grouped them into four functional conditions: I. Avoidance of school stimuli that generate negative affectivity; II. Avoidance of school situations that generate social aversion or fear of evaluation; II. Capturing the attention of significant others; and IV. Get tangible reinforcements outside of school. Given its tendency to coexist with internalizing disorders, it is essential to understand its correlation with school anxiety, which is one of the significant problems in the child and adolescent population. In this way, the present study aims to identify the probability of predictive capacity of school anxiety on high school refusal. There were 1786 participants (51% men) aged 15 to 18 years (MAge = 16.31; SD = 1.00). The instruments administered were the Spanish version of the School Refusal Assessment Scale-Revised (SRAS-R-C; Gonzálvez et al., 2016) and the School Anxiety Inventory (IAES; García-Fernández et al., 2011). The results reveal that depending on the dimension of school anxiety evaluated, it acts as a negative or positive predictor of school refusal, also depending on the type of school refusal assessed. These findings highlight the connection between the avoidance of negative affectivity associated with school and the experience of anxiety in various school settings, emphasizing the need to address both school refusal and anxiety in the educational setting.

IntroductionPatients with Cushing’s syndrome (CS) in remission show sustained fatigue, myopathy, and an increased prevalence of sarcopenia. The mechanisms that determine these persistent muscle problems are not well known. We aimed to identify circulating microRNAs (miRNAs) with differential expression that could be potential biomarkers for the diagnosis and/or prognosis in CS.Patients and methodsThirty-six women in sustained remission for 13 ± 7 years (mean ± SD) from CS, with a median age (IQ range) of 51 (45.2–60) years and mean ± SD BMI of 27 ± 4 Kg/m2, and 36 matched healthy controls were investigated. In 7 patients sarcopenia was present according to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. Small RNA libraries were generated and indexed using a modified Illumina TruSeq small RNA-sequencing protocol. MiRNAs were identified in plasma using bioinformatic analysis, and validation was carried out using RT-qPCR. For the validation, Taqman probes were performed on QuantStudio 5 equipment (Applied Biosystems).ResultsIn a first discovery group using RNA-sequencing, plasma samples of 18 CS patients and 18 healthy subjects were investigated; circulating miR-28-5p, miR-495-3p and miR-654-5p were upregulated in CS patients as compared with controls (p

ABSTRACT The modulation of actin polymerization is a common theme among microbial pathogens. Even though microorganisms show a wide repertoire of strategies to subvert the activity of actin, most of them converge in the ones that activate nucleating factors, such as the Arp2/3 complex. Brucella spp. are intracellular pathogens capable of establishing chronic infections in their hosts. The ability to subvert the host cell response is dependent on the capacity of the bacterium to attach, invade, avoid degradation in the phagocytic compartment, replicate in an endoplasmic reticulum-derived compartment and egress. Even though a significant number of mechanisms deployed by Brucella in these different phases have been identified and characterized, none of them have been described to target actin as a cellular component. In this manuscript, we describe the identification of a novel virulence factor (NpeA) that promotes niche formation. NpeA harbors a short linear motif (SLiM) present within an amphipathic alpha helix that has been described to bind the GTPase-binding domain (GBD) of N-WASP and stabilizes the autoinhibited state. Our results show that NpeA is secreted in a Type IV secretion system-dependent manner and that deletion of the gene diminishes the intracellular replication capacity of the bacterium. In vitro and ex vivo experiments demonstrate that NpeA binds N-WASP and that the short linear motif is required for the biological activity of the protein.IMPORTANCEThe modulation of actin-binding effectors that regulate the activity of this fundamental cellular protein is a common theme among bacterial pathogens. The neural Wiskott–Aldrich syndrome protein (N-WASP) is a protein that several pathogens target to hijack actin dynamics. The highly adapted intracellular bacterium Brucella has evolved a wide repertoire of virulence factors that modulate many activities of the host cell to establish successful intracellular replication niches, but, to date, no effector proteins have been implicated in the modulation of actin dynamics. We present here the identification of a virulence factor that harbors a short linear motif (SLiM) present within an amphipathic alpha helix that has been described to bind the GTPase-binding domain (GBD) of N-WASP stabilizing its autoinhibited state. We demonstrate that this protein is a Type IV secretion effector that targets N-WASP-promoting intracellular survival and niche formation.

ABSTRACT Quantitation of cytomegalovirus (CMV) DNA load in specimens other than blood such as bronchoalveolar lavages, intestinal biopsies, or urine has become a common practice as an ancillary tool for the diagnosis of CMV pneumonitis, intestinal disease, or congenital infection, respectively. Nevertheless, most commercially available CMV PCR platforms have not been validated for CMV DNA detection in these specimen types. In this study, a laboratory-developed test based on Alinity m CMV (“Alinity LDT”) was evaluated. Reproducibility assessment using spiked bronchial aspirate (BAS) or urine samples showed low standard deviations of 0.08 and 0.27 Log IU/mL, respectively. Evaluating the clinical performance of Alinity LDT in comparison to a laboratory-developed test based on RealTime CMV (“RealTime LDT”) showed good concordance across 200 clinical specimens including respiratory specimens, intestinal biopsies, urine, and stool. A high Pearson's correlation coefficient of r = 0.92, a low mean bias of −0.12 Log IU/mL, a good qualitative agreement of 90%, and a Cohen's kappa value of 0.76 (substantial agreement) were observed. In separate analyses of the sample types BAS, tracheal aspirates, bronchoalveolar lavage, biopsies, and urine, the assay results correlated well between the two platforms with r values between 0.88 and 0.99 and a bias

Summary: Background: The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE. Methods: A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued. Findings: Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3–20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5–4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2–4.2). No patient died of recurrent PE (0%, 95% CI: 0–7.6%). Subgroup analyses showed that patients with diagnosis in 2021–2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45–5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19–4.49) had significantly higher rates of VTE recurrences. Interpretation: In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings. Funding: Sanofi and Rovi, Sanofi Spain.

El arquitecto colombiano German Samper Gnecco interiorizó la metodología del dibujar motivado por su encuentro con Le Corbusier en el atelier del 35 rue de Sèvres en París. Aquella tutela supuso un momento crucial en su formación como arquitecto, ya que desde entonces nunca abandonaría lo que sería uno de sus acervos más importantes: el dibujo a mano alzada. Pero ¿quién es German Samper?, ¿cuál ha sido el significado del dibujo para este arquitecto?, ¿cómo extrajo enseñanzas del dibujo? y ¿qué ha querido buscar y expresar Germán Samper con sus dibujos? En este artículo intentamos dar respuesta a estas cuestiones y pretendemos recuperar el reconocimiento de sus aportaciones gráficas –dispersas en la memoria colectiva– y la revisión de este fundamental arquitecto de origen colombiano que confirmó a través del dibujo, a representar, recrear y transformar la realidad arquitectónica; mediante una forma muy personal, a través de un discurso único.

Background: Metastatic hormone-sensitive prostate cancer (mHSPC) treatment has changed drastically during the last years with the emergence of androgen receptor–targeted agents (ARTAs). ARTA combined with androgen deprivation therapy has demonstrated better oncological and survival outcomes in these patients. However, the optimal choice among different ARTAs remains uncertain due to their analogous efficacy. Objectives: The objective of this study was to describe prostate-specific antigen (PSA) response and oncological outcomes of patients with mHSPC treated with apalutamide. Material and methods: Medical records from three different hospitals in Spain were used to conduct this study. Patients diagnosed with mHSPC and under apalutamide treatment were included between March 2021 and January 2023. Data regarding PSA response, overall survival (OS), and radiographic progression-free survival (rPFS) were collected and stratified by metastasis volume, timing, and stating. Results: 193 patients were included; 34.2% of patients were de novo mHSPC, and the majority was classified as m1b. The 18-month OS and rPFS were 92.5% and 88.9%, respectively. Patients with PSA levels ≤0.2 ng/ml showcased an 18-month OS rate of 98.7%, contrasting with 65.3% for those with PSA >0.2 ng/ml. Similar trends emerged for rPFS (97.4% and 53.7%, respectively). When differentiating between low-volume and high-volume metastasis, the OS rate stood at 98.4% and 80.7%, respectively, while the rPFS rates were 93% and 81.6%, respectively. No significant differences were found between groups stratified by metastasis timing. Conclusion: This real-world study on patients with mHSPC treated with apalutamide plus androgen deprivation therapy revealed robust oncological outcomes, aligning with the emerging evidence. The study's hallmark finding highlights the significance of rapid and deep PSA response as a predictor of improved oncological and survival outcomes.

Abstract Purpose The significant proportion of asymptomatic patients and the scarcity of genotypic analysis of lymphogranuloma venereum (LGV), mainly among men who have sex with men (MSM), triggers a high incidence of underdiagnosed patients, highlighting the importance of determining the most appropriate strategy for LGV diagnosis, at both clinical and economical levels. Materials and methods We conducted L1-L3 serovar detection by molecular biology in stored Chlamydia trachomatis-positive samples from MSM patients with HIV, another STI or belonging to a Pre-exposure prophylaxis program, to make a cost effectiveness study of four diagnostic strategies with a clinical, molecular, or mixed approach. Results A total of 85 exudates were analyzed: 35urethral (31 symptomatic/4 positive) and 50 rectal (22 symptomatic/25 positive), 70/85 belonging to MSM with associated risk factors. The average cost per patient was €77.09 and €159.55 for clinical (Strategy I) and molecular (Strategy IV) strategies respectively. For molecular diagnosis by genotyping of all rectal exudate samples previously positive for CT (Strategy II), the cost was €123.84. For molecular diagnosis by genotyping of rectal and/or urethral exudate samples from all symptomatic patients (proctitis or urethritis) with a previous positive result for CT (Strategy III), the cost was €129.39. The effectiveness ratios were 0.80, 0.95, 0.91, and 1.00 for each strategy respectively. The smallest ICER was €311.67 for Strategy II compared to Strategy I. Conclusions With 30% asymptomatic patients, the most cost-effective strategy was based on genotyping all rectal exudates. With less restrictive selection criteria, thus increasing the number of patients with negative results, the most sensitive strategies tend to be the most cost-effective, but with a high incremental cost-effectiveness ratio.

Abstract Background Hallux Valgus (HV) deformity is associated with misalignment in the sagittal plane that affects the first toe. However, the repercussions of the first toe hyperextension in HV have been scarcely considered. The purpose of this study was to provide evidence of the association between first-toe hyperextension and the risk of first toenail onycholysis in HV. Methods A total of 248 HV from 129 females were included. The extension of 1st MTP joint was measured while the patient was in the neutral position of the hallux using a two-branch goniometer. The classification of the HV severity stage was determined by the Manchester visual scale, and the height of the first toe in the standing position was measured using a digital meter. An interview and clinical examination were performed to collect information on the presence of onycholysis of the first toe. Results Of the 248 HV studied, 100 (40.3%) had onycholysis. A neutral extension > 30 degrees was noted in 110 (44.3%) HV. The incidence of onycholysis was higher in HV type C than in type B (p = 0.044). The probability of suffering onycholysis in the right foot was 2.3 times greater when the neutral position was higher than 30 degrees (OR = 2.3; p = 0.004). However, this was not observed in the left foot (p = 0.171). Onycholysis was more frequent in HV with more than 2 cm height of the first toe (p

Abstract Introduction Optical coherence tomography angiography (OCT-A) is a novel tool that allows the detection of retinal vascular changes. We investigated the association of macular vessel density (VD) in the superficial plexus assessed by OCT-A with measures of cerebrovascular pathology and atrophy quantified by brain magnetic resonance imaging (MRI) in non-demented individuals. Methods Clinical, demographical, OCT-A, and brain MRI data from non-demented research participants were included. We analyzed the association of regional macular VD with brain vascular burden using the Fazekas scale assessed in a logistic regression analysis, and the volume of white matter hyperintensities (WMH) assessed in a multiple linear regression analysis. We also explored the associations of macular VD with hippocampal volume, ventricle volume and Alzheimer disease cortical signature (ADCS) thickness assessed in multiple linear regression analyses. All analyses were adjusted for age, sex, syndromic diagnosis and cardiovascular variables. Results The study cohort comprised 188 participants: 89 with subjective cognitive decline and 99 with mild cognitive impairment. No significant association of regional macular VD with the Fazekas categories (all, p > 0.111) and WMH volume (all, p > 0.051) were detected. VD in the nasal quadrant was associated to hippocampal volume (p = 0.007), but no other associations of macular VD with brain atrophy measures were detected (all, p > 0.05). Discussion Retinal vascular measures were not a proxy of cerebrovascular damage in non-demented individuals, while VD in the nasal quadrant was associated with hippocampal atrophy independently of the amyloid status.

Abstract This paper evaluates the effectiveness and safety of XEN63 stent, either standalone or in combination with phacoemulsification, in patients with primary open-angle glaucoma (POAG). Eighty eyes from 80 patients with medically uncontrolled POAG were assigned to undergo XEN63 implant. The primary outcome was the surgical success, defined as an intraocular pressure (IOP) lowering from preoperative values ≥ 20% and an IOP absolute value between 6 and 18 mmHg, with or without antiglaucoma medications. Forty-three (53.7%) eyes underwent XEN63-standalone and 37(46.2%) eyes a XEN63 + Phacoemulsification procedure. Success rate was 68.8% (55/80) eyes in the overall study sample, 69.8% (30/43) eyes in the XEN63-standalone group; and 67.6% (25/37) eyes in the XEN63 + Phaco group (p = 0.6133). Preoperative IOP was significantly lowered from 22.1 ± 4.9 mmHg and 19.8 ± 3.7 mmHg to 14.7 ± 5.3 mmHg and 13.8 ± 3.4 mmHg in the XEN63-standalone and XEN63 + Phaco groups, respectively (p

Abstract Acquiring spatial control of nanoscopic metal clusters is central to their function as efficient multi-electron catalysts. However, dispersing metal clusters on surfaces or in porous hosts is accompanied by an intrinsic heterogeneity that hampers detailed understanding of the chemical structure and its relation to reactivities. Tethering pre-assembled molecular metal clusters into polymeric, crystalline 2D or 3D networks constitutes an unproven approach to realizing ordered arrays of chemically well-defined metal clusters. Herein, we report the facile synthesis of a {Pd3} cluster-based organometallic framework from a molecular triangulo-Pd3(CNXyl)6 (Xyl = xylyl; Pd 3 ) cluster under chemically mild conditions. The formally zero-valent Pd3 cluster readily engages in a complete ligand exchange when exposed to a similar, ditopic isocyanide ligand, resulting in polymerization into a 2D coordination network (Pd 3 -MOF). The structure of Pd 3 -MOF could be unambiguously determined by continuous rotation 3D electron diffraction (3D-ED) experiments to a resolution of ~1.0 Å (>99% completeness), showcasing the applicability of 3D-ED to nanocrystalline, organometallic polymers. Pd 3 -MOF displays Pd0 3 cluster nodes, which possess significant thermal and aerobic stability, and activity towards hydrogenation catalysis. Importantly, the realization of Pd 3 -MOF paves the way for the exploitation of metal clusters as building blocks for rigidly interlocked metal nanoparticles at the molecular limit.

Abstract Background Cardiac fibroblast activation protein (FAP) has an emerging role in heart failure (HF). A paradoxical reduction in its levels in pathological conditions associated with acute processes has been observed. We aimed to identify FAP cardiac tissue expression and its relationship with the main cardiac fibrosis-related signaling pathways, and to compare plasma FAP levels in acute and chronic HF patients. Methods Transcriptomic changes were assessed via mRNA/ncRNA-seq in left ventricle tissue from HF patients (n = 57) and controls (n = 10). Western blotting and immunohistochemistry were used to explore FAP protein levels and localization in cardiac tissue. ELISA was performed to examine plasma FAP levels in acute HF (n = 48), chronic HF (n = 15) and control samples (n = 7). Results FAP overexpression in cardiac tissue is related to the expression of molecules directly involved in cardiac fibrosis, such as POSTN, THBS4, MFAP5, COL1A2 and COL3A1 (P