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La cartografía geológica detallada, los levantamientos estratigráficos, la recolección de fósiles y el muestreo de roca para análisis geoquímicos fueron las herramientas utilizadas para reconocer las unidades litoestratigráficas y precisar los niveles de mayor in- terés de fosfatos en la región axial de la cordillera Oriental, en los alrededores de Tunja (Boyacá). Rocas sedimentarias con un rango estratigráfico situado entre el Cretácico y el Paleógeno representan esta parte de la cordillera Oriental, en algunos sectores cubiertas discordantemente por depósitos del Neógeno y el Cuaternario. Las unidades litoestratigrá- ficas de interés en fosfatos corresponden a la Formación Arenisca Dura y facies fino-granulares silíceas equivalentes, y las supra- yacentes formaciones Plaeners y Arenisca de Labor y Tierna pertenecientes al Grupo Guadalupe. Las fallas inversas con dirección preferencial NE-SW y vergencia tanto al SE como al NW, algunas con salto transcurrente (fa- llas de Chivatá, Cormenchoque, Puente Hamaca, Viracachá, Soapaga, Machetá, Río Icabuco y Hermitaño) y pliegues de carácter regional (sinclinales de Tunja, Cómbita y Úmbita) y local, igualmente orientados al NE-SW, son las estructuras dominantes en el área de estudio. El análisis geoestadístico de los datos geoquímicos de fluorescencia de rayos X (FRX) realizado a 299 muestras de roca de las unidades de interés para determinar fosfatos, del Grupo Guadalupe, permitió definir cuatro sectores con potencial mineral alto a medio de P2O5: 1) zona de Turmequé, Nuevo Colón y Tibaná, con 10,8-27,5 %; 2) zona de Ciénega y Viracachá, con 6,74-10,8 %; 3) zona de Samacá y Cucaita, con 6,74-17,3 %, y 4) zona de Toca y Tuta, con 6,74-17,3 %.

The dissociative identity disorder (DID) can be considered a rare disorder because of its seemingly low prevalence. However, in recent years it points to the possible underdiagnosis because its complexity and confusion at the time of differential diagnosis. On the other hand, the malingering of mental psychopathology can have a major socio-economic and legal impact, particularly important in this type of disorder, given the inability it generates and its complex diagnostic. This paper refers the case of a patient admitted to the short-term hospitalization unit of Dr. Rodríguez Lafora Hospital (Madrid) with depressive symptoms. Then the patient seemed to become a TID case. The evaluation consisted of a psychological history and the application of the Structured Inventory of Malingered Symptoms (SIMS) and the Millon Clinical Multiaxial Inventory (MCMI-II). The results showed an altered personality profile as well as likely malingered symptoms, what prevented us from a DID diagnosis. In view of the results, possible implications of this case for the clinical setting are discussed.

A floristic survey was carried out in Yungas forests of the San José de Chijra river basin (Jujuy, Argentina). This is the first comprehensive study of vascular plants made in the area, a region relatively unknown in terms of vegetation. We present the results of this field survey; 172 species, 127 genera and 51 plant families are documented. Of these, 149 are native and 17 are endemic. Of the latter, three are endemic to Argentina, 11 to northestern Argentina, and three to Jujuy province. Families with the greatest number of species were Asteraceae (50), Solanaceae (13), Fabaceae (12), and Poaceae (8). According to IUCN criteria, two species are classified as threatened. Our data substantially increase our knowledge of the diversity of the regional flora and will provide an important contribution in developing conservation policy.

Los estudios de Criminología en España cuentan con un corto recorrido si se comparan con otras carreras. Cabe mencionar que a pesar de su “escasa edad”, en términos académicos, en las diferentes manifestaciones de esta titulación se observan cuestiones específicas que suponen el objeto del presente artículo. Por un lado, encontramos una cantidad de modificaciones legislativas que sirven para desarrollar e implantar multitud de títulos propios asociados a la especialidad. Por otro, existe la necesidad de ajustar las demandas sociales y laborales a los requerimientos de equivalencia exigida por la implantación efectiva del Espacio Europeo de Educación Superior (EEEs) en el año 2008. Asimismo, a lo largo de este artículo se analiza cómo, desde la propia Administración, se han tratado de establecer mecanismos que reajustaran las promulgaciones legislativas a las necesidades del mercado. Sin embargo, los estudios de criminología, a lo largo de su historia en España, primero como estudios propios y posteriormente como oficiales, nunca han terminado de verse cerrados. Al contrario, siempre han estado sometidos a continuos y cambios y ajustes de los destinatarios de este perfil a una realidad volátil. Muchos, por ejemplo, se planean a día de hoy si el grado, de 240 créditos ECTS, muestra similitudes o diferencias con aquellas titulaciones propias y los estudios de segundo ciclo del pasado. Por ello en el presente artículo también se establecen, a modo de reflexión, se trata de analizar si este tipo de estudios encuadraría en la promulgación del Real Decreto 43/2015.

Dada la refractariedad que muestran los criminales comunes, especialmente violentos y no diagnosticados de patologías mentales incapacitantes, a los tratamientos e intervenciones clínicas, se pretende en este trabajo evaluar su grado de sensibilidad al refuerzo y al castigo, así como su impulsividad, y poner ambos elementos en relación con otras posibles alteraciones de la personalidad. Para tal fin, se trabaja con una muestra discreta de personas que actualmente cumplen condena en cárceles españolas por crímenes muy violentos, siendo la condición básica de su selección la de haber asesinado, al menos, a dos personas, ya sea en el mismo evento o en eventos alternos. Se plantea la hipótesis de que las personalidades violentas caracterizadas por una ansiedad elevada muestran mayor sensibilidad al refuerzo y al castigo que aquellas otras de corte más propiamente antisocial. Sin embargo, detectamos un claro control del sesgo cognitivo por parte de estas personas en las pruebas estándar, validadas para población convencional, pero no específicamente para sujetos de estas características.

Abstract: Elevated levels of the NAD+-generating enzyme nicotinamide phosphoribosyltransferase (NAMPT) are a common feature across numerous cancer types. Accordingly, we previously reported pervasive NAD+ dysregulation in multiple myeloma (MM) cells in association with upregulated NAMPT expression. Unfortunately, albeit being effective in preclinical models of cancer, NAMPT inhibition has proven ineffective in clinical trials because of the existence of alternative NAD+ production routes using NAD+ precursors other than nicotinamide. Here, by leveraging mathematical modeling approaches integrated with transcriptome data, we defined the specific NAD+ landscape of MM cells and established that the Preiss-Handler pathway for NAD+ biosynthesis, which uses nicotinic acid as a precursor, supports NAD+ synthesis in MM cells via its key enzyme nicotinate phosphoribosyltransferase (NAPRT). Accordingly, we found that NAPRT confers resistance to NAD+-depleting agents. Transcriptomic, metabolic, and bioenergetic profiling of NAPRT-knockout (KO) MM cells showed these to have weakened endogenous antioxidant defenses, increased propensity to oxidative stress, and enhanced genomic instability. Concomitant NAMPT inhibition further compounded the effects of NAPRT-KO, effectively sensitizing MM cells to the chemotherapeutic drug, melphalan; NAPRT added-back fully rescues these phenotypes. Overall, our results propose comprehensive NAD+ biosynthesis inhibition, through simultaneously targeting NAMPT and NAPRT, as a promising strategy to be tested in randomized clinical trials involving transplant-eligible patients with MM, especially those with more aggressive disease.

Abstract Somatic mutations of hematopoietic cells in the peripheral blood of normal individuals refer to clonal hematopoiesis of indeterminate potential (CHIP), which is associated with a 0.5–1% risk of progression to hematological malignancies and cardiovascular diseases. CHIP has also been reported in Multiple Myeloma (MM) patients, but its biological relevance remains to be elucidated. In this study, high-depth targeted sequencing of peripheral blood from 76 NDMM patients revealed CHIP in 46% of them, with a variant allele frequency (VAF) ranging from ~ 1 to 34%. The most frequently mutated gene was DNMT3A, followed by TET2. More aggressive disease features were observed among CHIP carriers, who also exhibited higher proportion of high-risk stages (ISS and R-ISS 3) compared to controls. Longitudinal analyses at diagnosis and during follow-up showed a slight increase of VAFs (p = 0.058) for epigenetic (DNMT3A, TET2, and ASXL1) and DNA repair genes (TP53; p = 0.0123). A more stable frequency was observed among other genes, suggesting different temporal dynamics of CH clones. Adverse clinical outcomes, in term of overall and progression-free survivals, were observed in CHIP carriers. These patients also exhibited weakened immune T-cells and enhanced frailty, predicting greater toxicity and consequently shorter event-free survival. Finally, correlation analysis identified platelets count as biomarker for higher VAF among CHIP carriers, regardless of the specific variant. Overall, our study highlights specific biological and clinical features, paving the way for the development of tailored strategies for MM patients carrying CHIP.

Abstract Nuclear three dimensional (3D) folding of chromatin structure has been linked to gene expression regulation and correct developmental programs, but little is known about the 3D architecture of sex chromosomes within the nucleus, and how that impacts their role in sex determination. Here, we determine the sex-specific 3D organization of the model brown alga Ectocarpus chromosomes at 2 kb resolution, by mapping long-range chromosomal interactions using Hi-C coupled with Oxford Nanopore long reads. We report that Ectocarpus interphase chromatin exhibits a non-Rabl conformation, with strong contacts among telomeres and among centromeres, which feature centromere-specific LTR retrotransposons. The Ectocarpus chromosomes do not contain large local interactive domains that resemble TADs described in animals, but their 3D genome organization is largely shaped by post-translational modifications of histone proteins. We show that the sex determining region (SDR) within the U and V chromosomes are insulated and span the centromeres and we link sex-specific chromatin dynamics and gene expression levels to the 3D chromatin structure of the U and V chromosomes. Finally, we uncover the unique conformation of a large genomic region on chromosome 6 harboring an endogenous viral element, providing insights regarding the impact of a latent giant dsDNA virus on the host genome’s 3D chromosomal folding.

Improving education through virtual reality is challenging due to the high costs of developing systems and the lack of teacher engagement in project conception. This project introduces and evaluates a system that enables teachers to create their own lessons in virtual reality without prior programming knowledge, addressing these challenges. By integrating Learning Management tools, Learning Analytics, and Multi-user Connection Servers, we developed a system that allows multiple users to coexist in the same virtual environment and perform various tasks. Our system also enables educators to evaluate students based on their behavior. In EduVR, teachers can configure activities in advance and retrieve results. Heuristic evaluations of EduVR’s integrated environment design have demonstrated its potential as a model for developing new educational platforms, setting a new standard for virtual reality educational systems.

The ability of immune cells to expand numerically after infusion distinguishes adoptive immunotherapies from traditional drugs, providing unique therapeutic advantages as well as the potential for unmanageable toxicities. Here, we describe a case of lethal hyperleukocytosis in a patient with neuroblastoma treated on phase 1 clinical trial (NCT03294954) with autologous natural killer T cells (NKTs) expressing a GD2-specific chimeric antigen receptor and cytokine interleukin 15 (GD2-CAR.15). This patient was the first to be treated on dose level (DL) 5 and the first patient whose product was restimulated with K562-derived artificial antigen-presenting cells (aAPCs) instead of autologous peripheral blood mononuclear cells (PBMCs). 12 previously treated patients on DLs 1 through 4 did not experience significant toxicity. Our root-cause analysis revealed no genetic alterations of known clinical significance and excluded the possibility of clonal expansion due to insertional retroviral mutagenesis. We report that the use of aAPCs instead of PBMCs for CAR-NKT restimulation contributed to a hyperproliferative state associated with distinct gene expression that possibly led to explosive lymphocyte expansion and uncontrolled toxicity in the patient. These findings warrant the implementation of measures to control immune cell activation during manufacture of cell therapy products, especially those armed with transgenic cytokines.

The present study shows the genomic characterization of three pathogenic Escherichia coli hybrid strains. All strains were previously characterized as diarrheagenic pathotypes (DEC), obtained from feces. The three sequenced strains have genes that encode adhesins (fimH and iha) and iron uptake systems (iucC and iutA). Antibiotic resistance genes were also found for fluoroquinolone and aminoglycoside families in the three strains. The presence of genomic islands (GIs) in the sequenced study strains presented 100% identity (Ec-25.2) and 99% identity (Ec-36.1) with previously reported Extraintestinal Pathogenic E. coli (ExPEC) strains. The Ec-36.4 strain shared a 99% identity with GI from the Enterotoxigenic E. coli (ETEC) pathotype of the diarrheagenic E. coli strain. Ec-25.2 belongs to ST69 and harbors a FimH27 variant, while Ec-36.1 and Ec-36.4 belong to ST4238 and share a FimH54 variant. Four incompatibility groups associated with conjugative plasmids were identified (IncFIB, IncF11, IncI1, and IncB/O/K/Z), as well as Insertion Sequences and MITEs elements.

The advent and success of new drugs for treating HER2-positive metastatic breast cancer has led to a constant improvement in disease and progression-free survival as well as overall survival. Despite these advantages, the overall survival and quality of life of patients with HER2-positive breast cancer brain metastases are significantly worse than the ones of patients with HER2-positive breast cancer metastases outside the brain. For this reason, prevention and treatment of brain metastasis remain a major clinical challenge and the keys to further improving the clinical and survival outcomes of HER2-positive breast cancer patients. This review discusses the etiopathogenesis of brain metastasis, the currently available treatments, and the future perspective on new treatment strategies and diagnostic tools.

Se estudió el efecto de la aspersión foliar de nanoestructuras con zinc (ZnO-NE) en el crecimiento de plántulas de pepino en invernadero. Los tratamientos fueron cuatro soluciones elaboradas mediante nanoestructuras con zinc (ZnO-NE) obtenidas por microondas profesional (MP) y doméstico (MD), y por precipitación directa (PD); el testigo positivo (TP) fue fertilizante comercial (ZnSO4) y negativo (TN) agua. Semillas de pepino se sumergieron 2 h en la solución con la fuente respectiva de Zn2+ (30 mg L-1) y se sembraron en contenedores de poliestireno con turba y perlita (1:1 v/v), en invernadero. Las plántulas con dos hojas verdaderas se asperjaron con las soluciones correspondientes, cada siete días durante tres semanas. Se presentó menor altura de plántula en TN y mayor diámetro de tallo con ZnO-NE de MD. Las ZnO-NE de MD y PD produjeron hojas más anchas (6.98 y 6.89 mm), PD hojas de mayor longitud (6.01 mm); las plántulas tratadas con ZnO-NE de MP y MD aumentaron el área foliar (360.86 y 313.82 cm-2). Las tres fuentes de ZnO-NE incrementaron la longitud de raíz, y el volumen de raíz destacó en TP (10.2 mL). La biomasa fresca en raíz fue mayor con ZnO-NE de MD (3.54 g). Todas las fuentes de Zn mejoraron el peso fresco y seco del tallo; el peso fresco (6.5 g) y seco (0.85 g) de hoja resaltó con ZnO-NE de PD. La aspersión foliar con ZnO-NE es una alternativa para mejorar el crecimiento y producción de biomasa en plántulas de pepino cultivadas en invernadero.

Background: COVID-19 reduces lung functionality causing a decrease of blood oxygen levels (hypoxemia) often related to a decreased cellular oxygenation (hypoxia). Besides lung injury, other factors are implicated in the regulation of oxygen availability such as pH, partial arterial carbon dioxide tension (PaCO2), temperature, and erythrocytic 2,3-bisphosphoglycerate (2,3-BPG) levels, all factors affecting hemoglobin saturation curve. However, few data are currently available regarding the 2,3-BPG modulation in SARS-CoV-2 affected patients at the hospital admission. Material and methods: Sixty-eight COVID-19 patients were enrolled at hospital admission. The lung involvement was quantified using chest-Computer Tomography (CT) analysed with automatic software (CALIPER). Haemoglobin concentrations, glycemia, and routine analysis were evaluated in the whole blood, while partial arterial oxygen tension (PaO2), PaCO2, pH, and HCO3− were assessed by arterial blood gas analysis. 2,3-BPG levels were assessed by specific immunoenzymatic assays in RBCs. Results: A higher percentage of interstitial lung disease (ILD) and vascular pulmonary-related structure (VRS) volume on chest-CT quantified with CALIPER had been found in COVID-19 patients with a worse disease outcome (R = 0.4342; and R = 0.3641, respectively). Furthermore, patients with lower PaO2 showed an imbalanced acid-base equilibrium (pH, p = 0.0208; PaCO2, p = 0.0496) and a higher 2,3-BPG levels (p = 0.0221). The 2,3-BPG levels were also lower in patients with metabolic alkalosis (p = 0.0012 vs. no alkalosis; and p = 0.0383 vs. respiratory alkalosis). Conclusions: Overall, the data reveal a different pattern of activation of blood oxygenation compensatory mechanisms reflecting a different course of the COVID-19 disease specifically focusing on 2,3-BPG modulation.

ABSTRACT Objective This study aims to describe patterns, sources, and reasons for cannabis use among cancer patients during active treatment (+CDTX) compared to no‐use during active treatment (−CDTX). Methods Data are from 385 surveys collected via REDCap during phase I of an ongoing study among adult cancer patients seen at an NCI‐designated comprehensive cancer center within the last 5 years of treatment. A harmonized survey was created with 11 other NCI centers to assess cannabis use patterns, sources, and reasons for use. Sociodemographics and cancer details were also collected via self‐report. Descriptive statistics were calculated and stratified by +/−CDTX. Chi‐squared tests were conducted to compare proportions between groups. Results Among the sample [49.5 years (SD 15.9); 53.0% male; and 41.6% Hispanic/Latino], 41.0% + CDTX and 59.0% −CDTX. A majority (71.8%) of +CDTX initiated use before diagnosis versus 44.1% in −CDTX (p

Aging is one of the main risk factors for neurodegenerative disorders, which represent a global burden on healthcare systems. Therefore, identifying new strategies to slow the progression of brain aging is a compelling challenge. In this article, we first assessed the potential anti-aging effects of the Citrus flavanone naringenin (NAR), an activator of the enzyme sirtuin-1 (SIRT1), in a 3R-compliant and short-lived aging model (i.e., the nematode C. elegans). Then, we investigated the preventive effects of a 6-month treatment with NAR (100 mg/kg, orally) against brain aging and studied its mechanism of action in middle-aged mice. We demonstrated that NAR (100 μM) extends lifespan and improves healthspan in C. elegans. In the brain of middle-aged mice, NAR promotes the activity of metabolic enzymes (citrate synthase, cytochrome C oxidase) and increases the expression of the SIRT1 enzyme. Consistently, NAR up-regulates the expression of downstream antioxidant (Foxo3, Nrf2, Ho-1), anti-senescence (p16), and anti-inflammatory (Il-6, Il-18) markers. Our findings support NAR supplementation to slow the signs of brain aging.