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Abstract Recent studies have shown that the tumor extracellular matrix (ECM) associates with immunosuppression, and that targeting the ECM can improve immune infiltration and responsiveness to immunotherapy. A question that remains unresolved is whether the ECM directly educates the immune phenotypes seen in tumors. Here, we identify a tumor-associated macrophage (TAM) population associated with poor prognosis, interruption of the cancer immunity cycle, and tumor ECM composition. To investigate whether the ECM was capable of generating this TAM phenotype, we developed a decellularized tissue model that retains the native ECM architecture and composition. Macrophages cultured on decellularized ovarian metastasis shared transcriptional profiles with the TAMs found in human tissue. ECM-educated macrophages have a tissue-remodeling and immunoregulatory phenotype, inducing altered T cell marker expression and proliferation. We conclude that the tumor ECM directly educates this macrophage population found in cancer tissues. Therefore, current and emerging cancer therapies that target the tumor ECM may be tailored to improve macrophage phenotype and their downstream regulation of immunity.

Abstract Using experiments and theory, we investigate the behavior of nonlinear acoustic modes in a physical system composed of an array of three coupled acoustic waveguides, two of which are externally driven with two different frequencies. Nonlinear modes with frequency given by linear combinations of the driving frequencies are realizations of so-called logical phi-bits. A phi-bit is a two-state degree of freedom of an acoustic wave, which can be in a coherent superposition of states with complex amplitude coefficients, i.e., a qubit analogue. We demonstrate experimentally that phi-bit modes are supported in the array of waveguides. Using perturbation theory, we show that phi-bits may result from the intrinsic nonlinearity of the material used to couple the waveguides. We have also isolated possible effects on phi-bit states associated with the systems’ electronics, transducers and ultrasonic coupling agents used to probe the array and that may introduce extrinsic nonlinearities. These extrinsic effects are shown to be easily separable from the intrinsic behavior. The intrinsic behavior includes sharp jumps in phi-bit phases occurring over very narrow ranges of driving frequency. These jumps may also exhibit hysteretic behavior dependent on the direction of driving frequency tuning. The intrinsic states of phi-bits and multiple nonlinearly correlated phi-bits may serve as foundation for robust and practical quantum-analogue information technologies.

How the bone marrow microenvironment evolves during induction chemotherapy to facilitate acute lymphoblastic leukaemia (ALL) survival remains unclear. Here the authors show that adipocytes emergent during ALL therapy aid the survival of ALL cells through a restrictive effect on the ALL proteome.

This study investigates the pedagogical competence of elementary school teachers in integrating educational technology in the classroom. Pedagogical competence involves creating effective learning environments, designing activities that cater to different learning styles, and using appropriate teaching strategies. Technology integration in education has opened up new opportunities for interactive learning experiences. The study found that elementary school teachers had a positive attitude towards educational technology, and most reported having high levels of competence in its use. However, the level of pedagogical competence toward educational technology varied significantly among teachers. Hence, the study emphasizes the need for programs and interventions to improve teachers' pedagogical competence in integrating educational technology into their teaching practices. Teachers must identify appropriate technological tools and resources to effectively incorporate educational technology to support their teaching objectives and engage students in meaningful learning experiences. Teachers must also assess students' technical skills and design activities appropriate for their technological competency level. The study recommends that elementary school teachers undergo training to improve their pedagogical competence in using educational technology. Thus, integrating technology into education is crucial in providing high-quality education in the 21st century. Programs are needed to improve teachers' pedagogical competence in incorporating it into their teaching practices.

This study explores the integration of technology platforms in online modular learning and proposes an enhanced learning continuity framework using online teaching as an alternative delivery modality. The study captures participants' experiences related to online modular education through surveys by employing a qualitative approach. The findings demonstrate that integrating technological platforms enhances learning continuity. Online teaching offers flexible and accessible learning experiences, fostering effective teaching and learning. The study emphasizes the significance of comprehensive technical infrastructure, blended learning approaches, pedagogical and learner support services, continuous assessment, and a healthy learning environment in crafting the framework. The framework emphasizes robust technological infrastructure, training programs, blended learning approaches, pedagogical support, diverse assessment strategies, and a healthy learning environment by addressing challenges like the digital divide, technical difficulties, and lack of face-to-face interaction, flexibility, adaptability, and continuous evaluation are emphasized to address specific institutional and learner needs. Implementing the framework requires collaboration among educational institutions, policymakers, and communities to create inclusive online learning environments. Efforts should be made to ensure equitable access to reliable internet connections, support disadvantaged learners, and foster creativity through interactive activities. Monitoring and evaluation play a vital role in tracking progress and making informed decisions for improvement. This study provides a foundation for institutions to develop an enhanced learning continuity framework using online teaching. By optimizing the benefits of online modular learning while addressing challenges, the framework promotes effective teaching and learning in the online education landscape.

This study assessed the effectiveness of a professional development program for junior high school mathematics teachers in the Philippines and analyzed their achievement test results in Mathematics. The study aimed to identify the factors affecting the quality of mathematics instruction and propose solutions to these challenges. The study found that while most teachers were consistent in their lesson planning and content delivery, they need to improve their questioning techniques, differentiated techniques, and strategies to develop higher-order thinking skills. The study suggests that teachers need to enhance their teaching practices to achieve the K to 12 curriculum goals, prepare students for better work opportunities, and contribute to the nation's economy. Professional development programs can provide opportunities for mathematics teachers to increase their knowledge and confidence in the subject. By improving their teaching practices, teachers can help enhance the quality of mathematics education in the Philippines. This study highlights the challenges mathematics teachers face in the country and the need for professional development programs to help them improve their teaching practices. The findings have important implications for mathematics education in the country, which can help raise the quality of education and the nation's economy.

This study explored the relationship between mathematics performance and learning styles among Grade 8 students in the Philippines. The study used a descriptive correlation research design to achieve its objectives, which included determining the profile of Grade 8 students, identifying their learning styles, and examining the relationship between mathematics performance and age, gender, and learning styles. The data was collected through an adapted questionnaire from David Kolb's learning style inventory. The findings revealed no significant relationship between learning styles and academic performance in mathematics. However, it is worth noting that the lack of a significant relationship does not necessarily mean that there is no relationship at all. Motivation, teacher quality, and cultural background may also influence mathematics performance. The findings suggest that educators should consider students' different learning styles when developing effective teaching strategies to enhance mathematics performance among Grade 8 students. This study contributes to the literature on mathematics education and has practical implications for educators seeking to enhance their students' mathematics performance.

Abstract Background Cystic fibrosis (CF) has a vast and heterogeneous mutational spectrum in Europe. This variability has also been described in Spain, and there are numerous studies linking CFTR variants with the symptoms of the disease. Most of the studies analysed determinate clinical manifestations or specific sequence variants in patients from clinical units. Others used registry data without addressing the genotype–phenotype relationship. Therefore, the objective of this study is to describe the genetic and clinical characteristics of people with CF and to analyse the relationship between both using data from the rare disease registry of a region in southeastern Spain. Methods A cross-sectional study was carried out in people with a confirmed diagnosis of CF registered in the Rare Diseases Information System (SIER) of the Region of Murcia (Spain). The patients were classified into two genotypes according to the functional consequence that the genetic variants had on the CFTR protein. Results There were 192 people diagnosed with CF reported in the Region of Murcia as of 31 December 2018. Seventy-six genotypes and 49 different variants were described, with c.1521_1523delCTT (p. Phe508del) being the most common in 58.3% of the CF patients and 37.0% of the alleles. In addition, 67% of the patients were classified as a high-risk genotype, which was associated with a lower percentage of FEV1 (OR: 5.3; 95% CI: 1.2, 24.4), an increased risk of colonization by Pseudomonas aeruginosa (OR: 7.5; 95% CI: 1.7, 33.0) and the presence of pancreatic insufficiency (OR: 28.1; 95% CI: 9.3, 84.4) compared to those with a low-risk genotype. Conclusions This is the first study in Spain that describes the mutational spectrum and its association with clinical manifestations in patients with CF using data from a rare disease registry. The results obtained allow planning for the health resources needed by people with this disease, thus contributing to the development of personalized medicine that helps to optimize health care in CF patients.

Trichuriasis is considered a neglected tropical disease, being the second most common helminthiasis in humans. Detection of Trichuris in routine diagnosis is usually done by microscopic detection of eggs in fecal samples. Other molecular analyses are more reliable and could be used, but these analyses are not routinely available in clinical microbiology laboratories. The use of matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS) is increasing since the last decades due to its recent evidence as a potential role for reliable identification of microorganisms and a few nematodes. But, for parasites detection, normalized protocols and the acquisition and introduction of new species to the database are required. We carried out a preliminary study confirming the usefulness of MALDI-TOF MS for the rapid and reliable identification of Trichuris suis used as control and the creation of an internal database. To create main spectra profiles (MSPs), the different parts of five whipworms (esophagus and intestine) were used, developing different tests to verify the repeatability and reproducibility of the spectra. Thus, to validate the new internal database, 20 whipworms, separating the esophagus and intestine, were used, of which 100% were accurately identified as T. suis, but could not distinguish between both parts of the worm. Log score values ranged between 1.84 and 2.36, meaning a high-quality identification. The results confirmed that MALDI-TOF MS was able to identify Trichuris species. Additionally, a MALDI-TOF MS profile of T. suis proteome was carried out to develop the first internal database of spectra for the diagnosis of trichuriasis and other Trichuris spp.

Abstract Background Recent studies have reported the existence of a Trichuris species complex parasitizing primate. Nevertheless, the genetic and evolutionary relationship between Trichuris spp. parasitizing humans and Non-Human Primates (NHP) is poorly understood. The hypothesised existence of different species of Trichuris in primates opens the possibility to evaluate these primates as reservoir hosts of human trichuriasis and other putative new species of whipworms. Results In this paper, we carried out a morphological, biometrical and molecular study of Trichuris population parasitizing Macaca sylvanus from Spain based on traditional morpho-biometrical methods, PCA analysis and ribosomal (ITS2) and mitochondrial (cox1 and cob) DNA sequencing. Morphological results revealed that Trichuris sp. from M. sylvanus is Trichuris trichiura. Ribosomal datasets revealed that phylogenetic relationships of populations of Trichuris sp. from M. sylvanus were unresolved. The phylogeny inferred on mitochondrial datasets (partitioned and concatenated) revealed similar topologies; Thus, phylogenetic trees supported the existence of clear molecular differentiation between individuals of Trichuris sp. from M. sylvanus appearing in two different subclades. Conclusions Based on morphological parameters, biometrical measurements, and molecular sequence analysis, we conclude that the whipworms isolated from M. sylvanus were T. trichiura. Further, the evolutionary relationship showed that these worms belonged to two genotypes within the T. trichiura lineage. Since T. trichiura is of public health importance, it is important to carry out further studies to improve the understanding of its hosts range, evolution and phylogeography.

Prenatal folate exposure may alter epigenetic marks in the offspring. We aimed to evaluate associations between prenatal exposure to folic acid (FA) in preconception and in utero with cord blood DNA methylation in long interspersed nuclear element 1 (LINE-1) and Alu short interspersed nuclear elements (SINEs) as markers of global DNA methylation levels. Data come from 325 mother–child pairs participating in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015–2018). Pregnant women were asked about supplement use, including brand name and dose, one month before pregnancy (preconception) and through the trimesters of pregnancy. Maternal dietary folate intake was assessed using a validated food frequency questionnaire with additional questions for FA supplement use. Folate serum levels were measured in mothers at 24 weeks of gestation and in cord blood of newborns. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 5 LINE-1 and 3 Alu different elements. Associations were estimated using multivariable linear regression models. A reduction in methylation levels of LINE-1 in newborns was associated with the use of FA supplements below the recommended doses (<400 ug/day) during preconception (−0.50; 95% CI: −0.91, −0.09; P = 0.016), and from preconception up to 12 weeks of gestation (−0.48; 95% CI: −0.88, −0.08; P = 0.018). Maternal use of FA supplements above the tolerable upper intake level of 1000 ug/day from preconception until 12 weeks of gestation was also related to lower methylation in LINE-1 at birth (−0.77; 95% CI: −1.52, −0.02; P = 0.044). Neither FA supplement use after 12 weeks of gestation nor maternal total folate intake (diet plus supplements) were associated with global DNA methylation levels at birth. Maternal non-compliance with the use of FA supplement recommendations from preconception up to 12 weeks of gestation reduces offspring global DNA methylation levels at birth. [ABSTRACT FROM AUTHOR]