Victor (Japan)

We aimed to 1) investigate associations between leisure time physical activity level cumulated over 20 years and multiple plasma proteins and 2) explore if proteins significantly associated with physical activity are also associated with risk of imminent myocardial infarction (MI), long-term MI and mortality. In the cohort Uppsala Longitudinal Study of Adult Men (ULSAM), leisure time physical activity was self-reported at ages 50, 60, and 70. At age 70, 720 plasma proteins were analyzed in 782 participants with up to 19.3 years of follow-up for MI and 26.3 years follow-up for mortality. In the nested case-cohort study Markers of Imminent Myocardial Infarction (MIMI), plasma proteins were measured in disease-free individuals from six European cohorts. Cases (n=420) were those with acute MI within 6 months of a blood draw, with up to four cohort representatives per case (n=1,598). A higher level of leisure time physical activity level was inversely associated with 12 plasma proteins after adjusting for age, education, smoking and established cardiovascular risk factors (Bonferroni corrected p<0.000069). Of these 12 proteins, IL-6 was associated with increased incidence of imminent MI (HR 1.22 95%CI [1.09-1.37]), TNFRSF11A was associated with increased long-term MI incidence (HR 1.22 [1.01-1.48]) and 11 proteins were associated with increased mortality (HR 1.14-1.30 [1.01-1.42]). These findings confirm and extend our understanding of how physical activity could assert its beneficial effect on cardiovascular health through proteins involved with modulating inflammatory, immune and metabolic pathways. Further research is needed to explore the causal mechanisms behind these associations.

This report presents a comprehensive account of the Colleague AI Classroom pilot, a collaborative design (co-design) study that brought generative AI technology directly into real classrooms. In this study, AI functioned as a third agent, an active participant that mediated feedback, supported inquiry, and extended teachers' instructional reach while preserving human judgment and teacher authority. Over seven weeks in spring 2025, 21 in-service teachers from four Washington State public school districts and one independent school integrated four AI-powered features of the Colleague AI Classroom into their instruction: Teaching Aide, Assessment and AI Grading, AI Tutor, and Student Growth Insights. More than 600 students in grades 6-12 used the platform in class at the direction of their teachers, who designed and facilitated the AI activities. During the Classroom pilot, teachers were co-design partners: they planned activities, implemented them with students, and provided weekly reflections on AI's role in classroom settings. The teachers' feedback guided iterative improvements for Colleague AI. The research team captured rich data through surveys, planning and reflection forms, group meetings, one-on-one interviews, and platform usage logs to understand where AI adds instructional value and where it requires refinement.

La residencia médica es una etapa crucial y trascendental en todo médico que desea una especialidad, por ende, contar con un tutor íntegro y capaz es crucial para lograr el objetivo trazado. El Dr. Juan Leiva Goicochea es un reumatólogo peruano nacido en Trujillo, formó residentes de dicha especialidad durante un periodo de 10 años (2013-2022). Ejerció su especialidad de la mano con su labor académica. Fue íntegro en cuanto a su profesión y docencia. Inculcó a sus residentes una actitud crítica y heterodoxa del conocimiento actual. Es considerado como uno de los mejores reumatólogos del norte peruano. Este documento enfatiza la importancia de tener un tutor de residentes íntegro para un buen desempeño posterior del futuro especialista y algunas vivencias del residentado con el Dr. Leiva.

Mycobacterium abscessus is one of the leading causes of pulmonary infections caused by non-tuberculous mycobacteria. The ability of M. abscessus to establish a chronic infection in the lung relies on a series of adaptive mutations impacting, in part, global regulators and cell envelope biosynthetic enzymes. One of the genes under strong evolutionary pressure during host adaptation is ubiA, which participates in the elaboration of the arabinan domains of two major cell envelope polysaccharides: arabinogalactan (AG) and lipoarabinomannan (LAM). We here show that patient-derived UbiA mutations not only cause alterations in the AG, LAM, and mycolic acid contents of M. abscessus but also tend to render the bacterium more prone to forming biofilms while evading uptake by innate immune cells and enhancing their pro-inflammatory properties. The fact that the effects of UbiA mutations on the physiology and pathogenicity of M. abscessus were impacted by the rough or smooth morphotype of the strain suggests that the timing of their selection relative to morphotype switching may be key to their ability to promote chronic persistence in the host.IMPORTANCEMultidrug-resistant pulmonary infections caused by Mycobacterium abscessus and subspecies are increasing in the U.S.A. and globally. Little is known of the mechanisms of pathogenicity of these microorganisms. We have identified single-nucleotide polymorphisms (SNPs) in a gene involved in the biosynthesis of two major cell envelope polysaccharides, arabinogalactan and lipoarabinomannan, in lung-adapted isolates from 13 patients. Introduction of these individual SNPs in a reference M. abscessus strain allowed us to study their impact on the physiology of the bacterium and its interactions with immune cells. The significance of our work is in identifying some of the mechanisms used by M. abscessus to colonize and persist in the human lung, which will facilitate the early detection of potentially more virulent clinical isolates and lead to new therapeutic strategies. Our findings may further have broader biomedical impacts, as the ubiA gene is conserved in other tuberculous and non-tuberculous mycobacterial pathogens.

Simulations are commonly used to develop and evaluate video encryption algorithms. Although these approaches are useful for demonstrating theoretical feasibility and algorithm performance, they neglect practical challenges and real-world communication conditions. This oversight creates a critical gap in evaluating their effectiveness and security in practical applications. In this paper, we describe a novel, to the best of our knowledge, video encryption scheme that employs a modified chaotic Colpitts oscillator, a customized Josephus problem, and ribonucleic acid (RNA) operations, and is implemented in visible light communication (VLC) environment. The modified Colpitts oscillator reveals significant phenomena, the most prominent for this study being chaos. The encryption scheme involves block scrambling and pixel-level permutation employing a customized Josephus problem and a column and row shifting technique. Diffusion is then achieved through a custom Josephus problem-oriented RNA operation combined with basic RNA operations and cipher block chaining (CBC). Based on the results, we found that the customized Josephus problem-based permutation performed more efficiently than traditional methods, whereas the column and row shifting permutation was more robust. By eliminating key sequence coding and item-to-item operations, the proposed RNA operation reduces computational overhead. This video encryption scheme is proven to be effective and resilient at securing video data transmitted over the VLC channel, and it constitutes a significant advancement in areas such as surveillance, medical imaging, and military communication requiring robust secured video data.

Adrenal tuberculosis remains the main cause of primary adrenal insufficiency (PAI) in tuberculosis (TB)-prevalent regions. This case report details the presentation of PAI due to adrenal TB, where the etiological diagnosis involves Abdominal Computed Tomography (CT). A 37-year-old Peruvian woman with a history of TB contact displayed symptoms of adrenal insufficiency. PAI diagnosis was established, and CT imaging unveiled bilateral adrenal enlargement with calcifications. Treatment with prednisone and anti-TB therapy led to symptomatic improvement. Unfortunately, she succumbed to pneumonia after ten months of follow-up. Adrenal TB must be considered in endemic regions and in the presence of a TB history. CT serves as a valuable diagnostic tool, particularly in settings with limited resources, revealing adrenal enlargement and calcifications. In patients with PAI, epidemiological history of TB, and when a rapid biopsy is not feasible, CT proves to be a valuable diagnostic method.

El objetivo fue describir la importancia hacia las clases de Educación Física y la intención de ser físicamente activo entre sexos, así como su asociación con el nivel de AF semanal autopercibida. Un total de 77 estudiantes entre 13-15 años de ESO (edad media= 13.47 ± 0.563). Para valorar el grado de importancia y utilidad hacia las clases de Educación Física se utilizó el cuestionario IEF, la intención de ser físicamente activo se evaluó a través del cuestionario MIFA y se registró el nivel de AF moderada-vigorosa semanal autopercibida. Los resultados mostraron que los hombres obtuvieron medias más altas en la importancia atribuida a las clases de EF con respecto a las mujeres (p &lt;0.05). Además, se observó una fuerte asociación entre los instrumentos IEF (r = 0.326; p= 0.004), MIFA (r = .960, = 75; p &lt;0.001) y promedio de AF (r = 0.389, p= 0.001). Los chicos otorgan mayor importancia a las clases de EF lo que sugiere la necesidad de desarrollar estrategias que aumenten el interés de las chicas para promover una mayor intención de ser físicamente activas.

Mendelian randomization is being utilized to assess causal effects of polygenic exposures, where many genetic instruments are subject to horizontal pleiotropy. Existing methods for detecting and correcting for horizontal pleiotropy have important assumptions that may not be fulfilled. Built upon the core gene hypothesis, we developed MR Corge for performing sensitivity analysis of Mendelian randomization. MR Corge identifies a small number of putative core instruments that are more likely to affect genes with a direct biological role in an exposure and obtains causal effect estimates based on these instruments, thereby reducing the risk of horizontal pleiotropy. Using positive and negative controls, we demonstrated that MR Corge estimates aligned with established biomedical knowledge and the results of randomized controlled trials. MR Corge may be widely applied to investigate polygenic exposure-outcome relationships. An open-sourced R package is available at https://github.com/zhwm/MRCorge.

Abstract Heterozygous familial hypercholesterolemia (HeFH) is one of the most frequent monogenic disorders in the world, leading to premature atherosclerotic cardiovascular diseases (ASCVD). The aim of this meta-analysis was to evaluate the efficacy and safety of lipid lowering therapy (LLT) and achievement of low-density lipoprotein cholesterol (LDL-C) goal in children with HeFH. The main endpoint was efficacy of goal achievement for LDL-C and other lipid parameters: total cholesterol [TC], triglycerides [TG], high density lipoprotein cholesterol [HDL-C], apolipoprotein B [apo B] and lipoprotein(a) [Lp(a)]), and the LLT safety (adverse events [AEs], including endocrine function, and growth indices). The secondary endpoint was an effect of LLT on attainment of LDL-C goal treatment (&lt;3.5 mmol/L/130 mg/dL). A total of 41 studies with 4667 pediatric patients at mean age 12.08±2.4 years were included. 17 reported the efficacy and safety of LLT therapy compared to control, while the remaining assessed LLT through pre- and post-treatment. At median follow-up of 18.8 months, the group on LLT had significantly higher mean reductions of TC, LDL-C, TG, and increased HDL-C compared to control (-1.75 [-67,7 mg/dl], -1.84 [-71.2 mg/dl], -0.11 [-9.74 mg/dl], 0.08 mmol/L [3.1 mg/dl], respectively, p&lt;0.001 for all). In the subgroup analysis according to different types of LLT we observed a significantly higher mean reduction of LDL-C by statin combined with ezetimibe treatment, followed by PCSK9 inhibitors, statins in monotherapy, and monotherapy with ezetimibe (-2.48 [-95.9 mg/dl], -2.16 [-83.5 mg/dl], -2.03 [-78.5 mg/dl], and -1.50 mmol/L [-58 mg/dl], respectively, test for overall effect: p&lt;0.001). The pooled LDL-C was reduced by 33.44% (-2.14 mmol/L [-82.8 mg/dl], p&lt;0.001) and failed to reach the goal treatment (&lt;3.5 mmol/L) by 12.6% (95%CI, 12.4 – 12.9%). 38.7% of children achieved the LDL-C goal, 23.9% fell short by up to 10%, 10.7% experienced moderate failure (were over the LDL-C target between &gt;10-20%), and 26.7% failed by more than 20% to reach the LDL-C target. When comparing different regions, only Sweden and Greece achieved the LDL-C goal &lt;3.5 mmol/L in the follow-up, followed by the Netherlands, Norway, Poland, USA, UK, France, Spain, Belgium, and Austria (with the following additional required LDL-C reduction to be on the goal: 2.2%, 3.4%, 3.5%, 8.9%, 10.2%, 11.2%, 11.2%, 15%, 19.4%, respectively). For other investigated countries over 20% mean LDL-C reduction was required. All parameters related to endocrine function and demographic indices were unaffected by LLT therapy (p&gt;0.05). The adverse events were not reported significantly higher when compared to the control and the prevalence of therapy discontinuation was only 0.8%. In conclusion, despite the efficacy of LLT in children with HeFH and the low occurrence of discontinuation-related adverse events, achieving LDL-C treatment goals was relatively rare, with large differences between the investigated countries. These results underscore the importance of considering early combination therapy of statins and ezetimibe, and PCSK9 inhibitors (if available) to attain LDL-C goals effectively.

Acrylic resins dominated dentures technology for several decades. Due to their many disadvantages, new types of polymers, with better properties, suitable for dental prosthodontics applications were constantly attempted. The choice of polymeric materials and manufacturing technologies has experienced significant development in recent years. Different types of thermoplastic injected resins, light-cured resins, or the versatile high-performance polymers are several choices of novel materials for dentures manufacturing. CAD/CAM systems, both substractive and additive, are being considered the most promising choice for the future manufacturing of polymers in dentistry. The chapter is focused on presenting the choices of novel polymeric materials, their manufacturing technologies, and applications in prosthodontics.