Search

Abstract Purpose High-quality graduate medical education programs are essential to expand the care available to children with cancer worldwide. The authors used the Education Program Assessment Tool (EPAT), a standardized tool for evaluating pediatric hematology/oncology (PHO) fellowship programs, to describe the impact of the Accreditation Council for Graduate Medical Education International (ACGME-I) accreditation process. Methods The EPAT is a comprehensive, validated tool for evaluating the elements of PHO fellowship programs. The authors used the EPAT in May 2018 and December 2023 to compare the pre-accreditation and post-accreditation status of the Unidad Nacional de Oncología Pediátrica (UNOP) PHO fellowship program. Results The authors used the EPAT to identify program gaps and to prioritize interventions to meet ACGME-I accreditation standards. Before accreditation, the overall score of the UNOP PHO fellowship program was 77.2%. The highest score was for Hospital Infrastructure (86.4%) and the lowest score was for Research (63.0%). After accreditation, the overall score was 88.3%. Eight of the 10 EPAT domains had higher post-accreditation scores, with a significant improvement in domain scores overall (P

Abstract Background In SELECT-AXIS 2, upadacitinib improved the signs and symptoms of active non-radiographic axial spondyloarthritis (nr-axSpA) through 52 weeks versus placebo and was well tolerated. Here, we evaluated the efficacy and safety of upadacitinib through 2 years. Methods The study enrolled eligible adult patients with a clinical diagnosis of nr-axSpA who met the 2009 Assessment of SpondyloArthritis international Society (ASAS) classification criteria and had objective signs of active inflammation on magnetic resonance imaging (MRI) of sacroiliac joints and/or high-sensitivity C-reactive protein. Patients were randomized 1:1 to receive double-blinded treatment with upadacitinib 15 mg once daily (QD) or placebo for 52 weeks, after which all patients received open-label treatment with upadacitinib 15 mg QD. Efficacy results over 104 weeks were reported as observed (AO) and either AO with non-responder imputation (AO-NRI; binary endpoints) or AO with mixed-effect model for repeated measures (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized through week 104. Results Of 313 patients randomized and treated, 224 (continuous upadacitinib n = 117; placebo/upadacitinib n = 107) completed 104 weeks of treatment. In patients who received continuous upadacitinib, sustained improvement was observed through 2 years of treatment across efficacy endpoints including disease activity, pain, function, enthesitis, quality of life, and MRI measures of inflammation. At week 104, 57.1%, 59.0%, and 31.4% of patients achieved ASAS40 response, and low disease activity and inactive disease (as defined by Axial Spondyloarthritis Disease Activity Score), respectively (AO-NRI); week 104 outcomes were generally similar in patients who initially received placebo and were switched to upadacitinib at week 52. In total, 286 patients were exposed to ≥ 1 dose of upadacitinib, comprising 378.3 patient-years (PY) of exposure. Upadacitinib was generally well tolerated, with exposure-adjusted event rates (EAERs) for TEAEs, serious adverse events (AEs), and AEs leading to study drug discontinuation of 207.5, 8.7, and 5.3 events/100 PY, respectively. EAERs of TEAEs of special interest were broadly consistent with those reported through week 52. Conclusions Treatment with upadacitinib demonstrated consistent improvement and maintenance of treatment effect across efficacy endpoints through 2 years; no new safety signals were identified with additional exposure. Trial registration NCT04169373.

Andrés G Galindo-Padrón,1,* Helen Yarimet Lorenzo-Anota,2,3,* Mayte Rueda-Munguía,2,3 Alejandra García-Carrasco,1 Mabel Gaitán López,1 Eduardo Vázquez-Garza,2 Enrique Campos-González,4 Omar Lozano,2,3,5 Jorge L Cholula-Díaz1 1School of Engineering and Sciences, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico; 2Institute for Obesity Research, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico; 3School of Medicine and Health Sciences, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico; 4Departamento de Física, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac, Mexico; 5Cátedra de Cardiología y Medicina Vascular, Tecnologico de Monterrey, Monterrey, Nuevo León, México*These authors contributed equally to this workCorrespondence: Omar Lozano; Jorge L Cholula-Díaz, Email omar.lozano@tec.mx; jorgeluis.cholula@tec.mxBackground and Aim: Over the past years, noble metal-based nanoparticles have been extensively investigated for their applications in nanomedicine. However, there are still concerns about the potential adversities that these nanoparticles may present in an organism. In particular, whether they could cause an exacerbated cytotoxic response in susceptible tissues due to damage or disease, such as the heart, liver, spleen, or kidneys. In this regard, this study aims to evaluate the cytotoxicity of mono- and bimetallic nanoparticles of gold and silver (Au:Ag NPs) on healthy and hypertrophic cardiac H9c2 cells, and on healthy and metabolically activated macrophages derived from U937 cells. The main objective of this work is to explore the susceptibility of cells due to exposure to Au:Ag NPs in conditions representing cardiometabolic diseases.Methods: Au:Ag NPs were synthesized in different molar ratios (Au:Ag, 100:0, 75:25, 50:50, 25:75, 0:100) using starch as a capping and reducing agent. Their physicochemical properties were characterized through UV-vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), ζ-potential measurements, and transmission electron microscopy (TEM). Moreover, the effect of the metal-based nanoparticle exposure on healthy and hypertrophic H9c2 cells was measured by analyzing the cellular vitality, the loss of mitochondrial membrane potential (∆Ψm), and the production of mitochondrial reactive oxygen species (mROS).Results: The Au:Ag NPs did not affect the cell vitality of healthy or metabolically activated macrophages. On the contrary, healthy H9c2 cells showed decreased mitochondrial metabolism when exposed to NPs with higher Ag concentrations. Furthermore, hypertrophic H9c2 cells were more susceptible to the same NPs compared to their non-hypertrophic counterparts, and presented a pronounced loss of ∆Ψm. In addition, these NPs increased the production of mROS and regulated cell death in both cardiac cells.Conclusion: In conclusion, low doses of high-Ag load in Au:Ag NPs produced cytotoxicity on H9c2 cardiac cells, with hypertrophic cells being more susceptible. These results suggest that cardiac hypertrophic conditions are more prone to a cytotoxic response in the presence of bimetallic Au:Ag NPs compared to healthy cells. In addition, this work opens the door to explore the nanotoxicity of noble metal-based NPs in biological disease conditions.Keywords: cardiovascular disease, hypertrophic cardiomyoblasts, bimetallic nanoparticles, metabolically activated macrophages

The founder of soil mechanics, Karl Terzaghi, took the initiative in 1954 to contact the Danish engineer Laurits Bjerrum, requesting to meet. Terzaghi wanted to meet the engineer who had written a paper on the stability of the unusual Norwegian quick clays at the European Slope Congress in Stockholm. Bjerrum was 36 years old at the time, had a PhD and was already director of the NGI (Norges Geotekniske Institutt – Norwegian Geotechnical Institute). From his position as director of the NGI, he was actively involved in many varied consultancies, placing great value on the continuous interaction between practice and research. Bjerrum's strategy for establishing the NGI came from the experience of other research centres such as the BRS (Building Research Station) in Great Britain and Imperial College London. In addition, having lived through the Nazi occupation of Denmark, he was predisposed to be against the misuse of authority and established an open structure for the institute from its inception. Bjerrum was in close contact with the Norwegian Institution of Technology, and, in 1952, he succeeded in getting soil mechanics incorporated as a compulsory subject in the civil engineering degree. Subsequently, in 1960, the Chair of Soil Mechanics and Foundation Engineering was established. The first laboratory of this chair was equipped with material donated by the NGI. Bjerrum died young (54 years old), but he had built an excellent reputation through his work at the NGI and his contributions to international conferences, where he maintained a close relationship with the significant figures in geotechnics: Terzaghi, Skempton, Peck and Casagrande. He made regular trips to the USA, where he was a visiting professor at MIT (Massachusetts Institute of Technology) and received the highest international decorations.

El estudio de los útiles de escritura se ha centrado principalmente en el periodo romano, gracias a importantes hallazgos en entornos urbanos, como Augusta Emerita (Mérida, España), y en entornos rurales, por ejemplo Vindolanda (Reino Unido). Sin embargo, para el periodo altomedieval, esta área de investigación continúa siendo una asignatura pendiente debido a la escasez de hallazgos tanto en áreas urbanas como rurales. Las fuentes escritas disponibles para un estudio historiográfico de estos instrumentos son limitadas, y la arqueología no siempre puede proporcionar una tipología específica de estos utensilios, principalmente debido a la naturaleza perecedera de los materiales con los que se elaboraban, como el hueso o la madera. A través del análisis de los materiales encontrados en el poblado de Barajas (yacimiento El Encadenado, Madrid), ha sido posible identificar e investigar diversas herramientas de escritura, tales como un cálamo, un estilete y un tintero, todas datadas en la época altomedieval. Específicamente, estos materiales se sitúan en un periodo de transición entre la era visigoda y la era emiral (siglos VII-VIII). Este trabajo se ha llevado a cabo desde un enfoque multidisciplinar que incluye la presentación del asentamiento arqueológico y la descripción del contexto estratigráfico, el análisis arqueozoológico para determinar la elaboración de los materiales en hueso, la aplicación de la espectroscopía Raman para intentar identificar restos de tinta en el cálamo y, por último, la utilización de la Arqueología experimental con el objetivo de replicar estas herramientas teniendo en cuenta su función en la escritura. En este escrito presentamos por primera vez un análisis detallado de útiles documentados en un poblado de la Meseta Central, al mismo tiempo que reflexionamos sobre la sociedad y la economía rural en la que se encontró.

Abstract The resurgence of COVID-19 and the rise in severe outcomes emphasize the need for reliable prognostic markers to guide patient care and optimize ICU and hospital resources. This study investigates the potential of nasopharyngeal swabs to identify biomarkers that predict ICU admission or death in hospitalized COVID-19 patients. We analyzed nasopharyngeal exudates from 95 hospitalized patients in 2020 using high-plex RNA quantification on the NanoString® nCounter platform. Comparative analysis identified four genes, with KLRB1 (Killer cell lectin like receptor B1) (Odds Ratio OR 0.5, 95% CI: 0.27–0.96), along with age (OR 3.3, 95% CI: 1.25–8.93) emerging as independent prognostic markers in multivariate analysis. These findings were validated using qRT-PCR in an independent cohort of 168 patients hospitalized in 2022. While univariate analysis identified a significant association between KLRB1 expression and vaccination status (p

Abstract The film water, with an exceptional capacity to maintain a premelting, liquid-like state even under subzero conditions, provides a potential dynamic conduit for the movement of water in frozen soils. However, the distinctive structural and dynamic characteristics of film water have not been comprehensively elucidated. In this study, molecular dynamics (MD) simulations were conducted to examine the freezing of a system containing ice, water, silica, and gas. The simulations revealed that as the temperature approaches the melting point, the air-water interface tends to possess a thicker layer of unfrozen water, characterized by a higher diffusion coefficient and lower viscosity. In contrast, the film water near the silica-water interface tends to be thinner and remains relatively unaffected by temperature, with only one twentieth of the diffusion coefficient and nearly 20 times the viscosity observed at the air-water interface. These distinct characteristics resulted from the varying interactions between water molecules and their immediate surroundings. Consequently, the film water in proximity of the silica can be assumed to be relatively immobile compared to that of air-water interface. These findings have implications for the study of unsaturated frozen soil systems, in particular, the importance of considering the film water at the air-water interface in the modeling framework.

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and destruction of lung tissue, primarily attributed to tobacco smoking. However, other factors like biomass-burning smoke (BS) exposure are also implicated. COPD has been described as an accelerated aging disease, and telomere length is a biomarker of aging. Methods This study examined telomere length in 189 Mexican individuals, from which 93 developed COPD secondary to BS exposure (BE-COPD); the rest of the participants were exposed to BS but did not develop the disease. Lung function parameters were measured by spirometry, and relative telomere length (rTL) from peripheral blood DNA was determined using multiplex qPCR. Results Results showed rTL to inversely correlate with age (R2=-0.207, p = 0.006) and with the hours-a-day of BS exposure (R2=-0.297, p

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD‐1)/programmed cell death 1 ligand 1 (PD‐L1) pathway have transformed urothelial cancer (UC) therapy. The correlation between PD‐L1 expression and ICI effectiveness is uncertain, leaving the role of PD‐L1 as a predictive marker for ICI efficacy unclear. Among several ways to enhance the efficacy of ICI, trials are exploring combining ICIs with serine/threonine‐protein kinase mTOR (mTOR) inhibitors in different tumor types. The potential interaction between mTOR inhibitors and PD‐L1 expression in UC has not been well characterized. In our study, we investigated how phosphoinositide 3‐kinase (PI3K)/AKT/mTOR pathway inhibitors (TAK‐228, everolimus and TAK‐117) affect PD‐L1 expression and function in preclinical bladder cancer cell models. TAK‐228 increased cell surface levels of glycosylated PD‐L1 in all but one of the seven cell lines, regardless of baseline levels. TAK‐228 promoted the secretion of epidermal growth factor (EGF) and interferon‐β (IFNβ), both linked to PD‐L1 protein induction. Blocking EGF and IFNβ receptors reversed the TAK‐228‐induced PD‐L1 increase. Additionally, TAK‐228 enhanced IFN‐γ‐induced PD‐L1 expression and intracellular HLA‐I levels in some cells. TAK‐228‐treated bladder cancer cells exhibited resistance to the cytotoxic effects of peripheral blood mononuclear cells (PBMCs) and cluster of differentiation 8 (CD8)+ T cells. The addition of an anti‐PD‐L1 antibody diminished this resistance in T24 cells. Increased expression of PD‐L1 under TAK‐228 exposure was confirmed in patient‐derived explants (PDEs) treated ex vivo. These preclinical findings suggest that mTOR inhibition with TAK‐228 can increase PD‐L1 levels, potentially impacting the specific immune response against UC cells. This highlights the rationale for exploring the combination of mTOR inhibitors with ICIs in patients with advanced UC.

Abstract European Miocene tapirs (Perissodactyla, Tapiridae) are mainly documented by isolated and fragmentary remains, and little is known about the morphological variability of the various recognized species, in particular concerning the deciduous dentition. Here, we describe new material from three Vallesian (Late Miocene) sites of the Vallès-Penedès Basin (NE Iberian Peninsula): Creu de Conill 20 (CCN20; earliest MN9, 11.2 Ma), Can Llobateres 1 (CLL1; earliest MN10, 9.8 Ma), and Can Gambús-Illeta 5 (CGS-I5; MN10, 9.7–9.1 Ma). The described material, including previously reported specimens from CLL1, consists of a juvenile cranium as well as deciduous and permanent teeth, which are compared with those of Late Miocene tapirid species from Europe (Tapirus priscus, Tapirus antiquus, Tapiriscus pannonicus, Tapiriscus balkanicus, and Tapirus arvernensis), supporting an attribution to T. priscus. The Vallès-Penedès specimens provide further insight into the morphological variability of T. priscus, particularly regarding its deciduous dentition, as well as its distinction from T. arvernensis. Tapirus priscus occurred in Western Europe during the early and late Vallesian (MN9–MN10) and became extinct in Central Europe during the early Turolian (MN11), leaving a gap in the fossil record of Tapirus until the arrival of T. arvernensis at the MN13–MN14 transition. From a paleoecological perspective, the presence of Tapirus agrees with paleoenvironmental reconstructions of CLL1 as a humid and densely forested wetland/riparian forest with more open areas nearby, while the CGS-I5 material attests to the persistence of such kind of environments in the Vallès-Penedès Basin sometime into the late Vallesian. In contrast, the occurrence of Tapirus is at odds with previous paleoenvironmental inferences for CCN20, which indicated a more open and arid environment, suggesting that the earliest Vallesian in this basin was characterized by more humid and forested conditions than previously assumed (in further agreement with the roughly coeval site of Castell de Barberà).

In this paper, we describe the transition of all five course-sections of General Biology Laboratory I from "cookbook" surveys of taxonomic domains and kingdoms to course-based undergraduate research experiences that champion inquiry-based learning in "real world" environments. We achieved this by scaling-up lessons from a research-focused pilot section refined over three years to blend instruction with collaboration with community partners seamlessly. In terms of outcomes, students share data analyses directly with community partners, present posters at research conferences, publish research findings, and use project findings to successfully compete for placement in advanced summer research programs. This course structure benefits the students, the community partners, and the instructor. The community partners, in turn, are provided with free scientific consultations that advance data-driven strategies and empower adaptive management of localized environmental issues. The instructor benefits from the opportunity to contribute their unique disciplinary expertise toward the collaborative design and shared success of a modular course.

En los últimos años, el uso de sistemas basados en Inteligencia Artificial, como ChatGPT, ha ido ganando popularidad entre los estudiantes de educación superior, en parte porque les permite optimizar el tiempo requerido para el trabajo académico. El objetivo de este estudio ha sido determinar la frecuencia de uso de ChatGPT por parte de estudiantes universitarios con fines académicos y si existen diferencias estadísticamente significativas en el uso según el género, la edad, el rendimiento académico, el año académico y el grado de los participantes. Entre una muestra de 507 estudiantes universitarios, los resultados mostraron un uso moderadamente bajo de ChatGPT con fines académicos, aunque se encontraron diferencias significativas basadas en variables personales. Específicamente, se encontró un uso estadísticamente mayor de ChatGPT con fines académicos en hombres (en comparación con mujeres), en estudiantes de cursos intermedios (en comparación con estudiantes que acaban de comenzar o están terminando sus estudios) y en estudiantes inscritos en el programa de grado de Educación Primaria (en comparación con otros grados asociados con el campo educativo). No se encontraron diferencias significativas basadas en la edad. Estos hallazgos destacan la necesidad de establecer el perfil de las personas que más utilizan los sistemas basados en IA para detectar y prevenir posibles comportamientos deshonestos, como el plagio o el fraude en tareas, y así promover un uso responsable de dichas herramientas entre los estudiantes de educación superior.

The electrorheological (ER) characterization of low-viscosity fluids is paramount for producing micro- and nanoscale products through electrohydrodynamic (EHD) techniques, such as EHD-jet printing, electrospray, and electrospinning. Key properties such as viscosity, surface tension, dielectric properties, electrical conductivity, and relaxation time significantly influence both the quality and properties of the final products and the efficiency of the industrial process. ER characterization is essential for studying the macroscopic effects of the interaction between these physicochemical properties under controlled flow kinematics. Researchers may face several technical challenges in performing rigorous ER characterization of moderate conductive fluids typically used in EHD processes. This characterization is crucial for formulating inks compatible with these processes and for understanding fluid dynamics in EHD processes to ensure stable printing conditions and achieve high-resolution, accurate prints. This work highlights the inherent limitations of current ER cells and proposes methodologies to mitigate their impact on measurement accuracy. Furthermore, we propose the use of microfluidic devices as a solution for the ER characterization of moderate conductive fluids.

The coastal habitats in the southern Gulf of Mexico face multiple threats, such as rising water temperatures, acidification, increased turbidity, invasive species and pollutants. This imperils the biodiversity of beaches, wetlands and coral reefs. To address this, there is a need for comprehensive baseline information on marine biodiversity. Several reefs in the Gulf of Mexico have been extensively studied, yet smaller reefs on the Yucatan continental shelf lack thorough exploration despite their ecological significance. These reefs serve as crucial biodiversity hotspots influenced by environmental characteristics, receiving diverse taxa from the Gulf of Mexico.The macroalgae study at the Bank of Campeche dates back to the 1950s, but comprehensive investigations have been sporadic. The recent study aims to fill this gap, contributing to the taxonomic inventory of the area's benthic macroflora. Methodologically, extensive sampling across eight reefs was conducted, collecting and preserving macroalgae samples for identification in the laboratory.The study documented 90 infrageneric taxa across the reefs, with Cayo Arenas exhibiting the highest species count. Additionally, three new distribution reports for Mexico were identified in the region. The distribution of species varied amongst locations, with few species in common even amongst geographically proximate reefs. The diversity found in these reefs slightly trails behind other studied regions, but surpasses previous reports for the Campeche Bank.It is important to emphasise that the significance of this study lies in its focus on remote reefs with complicated and costly access logistics. Additionally, it is one of the first publicly available datasets published for this region.The study aligns with existing literature on prevalent families in reef environments and highlights differences in species distribution, based on depth variations amongst reefs. The findings of new distribution records in the region and the distinctiveness of localities despite their proximity underscore the unique ecological dynamics of these reefs.These reefs are located in remote and difficult-to-access areas, highlighting the importance of the data obtained on their biodiversity and conservation status. This work presents for the first time a list of macroalgae for the reefs of Banco Nuevo, Banco Obispo, Banco Pera and Serpientes Reef. Three new distribution reports for Yucatan were identified at the Banco Obispo reef: Botryocladia shanksii E. Y. Dawson, Ceratodictyon scoparium (Montagne & Millardet) R. E. Norris and Asteromenia peltata (W. R. Taylor) Huisman & Millar and a new report for the Mexican Atlantic, Herposiphonia parca Setchell at the Triángulo Oeste reef. This results in distinct algal communities compared to other reefs in the region, emphasising their ecological significance and the need for continued research and conservation efforts. To our knowledge, this is one of the first interoperable datasets being published on the marine algae of the southern Gulf of Mexico reef ecosystems.