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Circulating tumor cells (CTCs) and tumor-derived extracellular vesicles (tEVs) are two crucial methodologies of liquid biopsy. Given their distinct size differences and release dynamics, CTCs and tEVs potentially offer synergistic capabilities in the non-invasive detection of differentiated thyroid cancer (DTC), a typically indolent tumor. We present the Combined DTC CTC/tEV Assay, integrating dual liquid biopsy processes: i) DTC CTC enrichment by Click Chips, followed by analysis of seven DTC-specific genes, and ii) DTC tEV enrichment by Click Beads, succeeded by mRNA cargo quantification in DTC tEVs. This method utilizes click chemistry, leveraging a pair of biorthogonal and highly reactive functional motifs (tetrazine, Tz, and trans-cyclooctene, TCO), to overcome the challenges encountered in the conventional immunoaffinity-based enrichment of CTCs and tEVs. The Combined DTC CTC/tEV Assay synergistically combines the diagnostic precision of CTCs with the sensitivity of tEVs, demonstrating superior diagnostic accuracy in DTC detection and boasting an AUROC of 0.99. This outperforms the individual diagnostic performance of using either DTC CTC or DTC tEV alone. This integration enables full utilization of a patient's blood sample, and marks a significant evolution in the development of nanomaterial-based liquid biopsy technologies to address challenging unmet clinical needs in cancer care.

Abstract In the present study, Pušnik et al. investigated whether the XBB.1.5-adapted booster can overcome the persistent imprinting of SARS-CoV-2 immunity by wild-type based vaccines. The findings demonstrate increased plasma neutralization against the homologous variant following the booster vaccination. Formation of de novo humoral response against the mutated epitopes of XBB.1.5 variant’s surface proteins was observed in 3/20 individuals. The booster vaccination had no significant effect on T-cell response.

Abstract The understanding of the role played by extracellular vesicles (EVs) in different tissues has improved significantly in the last years, but remains limited concerning the conjunctiva, a complex eye tissue whose role is pivotal for corneal protection. Here, we conducted a comparative study to isolate and characterize EVs from human conjunctival epithelial (IM-HConEpiC) and human conjunctival mesenchymal stromal cell (Conj-MSCs) secretomes using different isolation methods: differential ultracentrifugation (UC), and a combination of ultrafiltration (UF) with precipitation or size exclusion chromatography (SEC). EVs were characterized by total protein content, size, morphology, and expression of protein markers. EV functional effect was tested in an in vitro oxidative stress model. We successfully recovered EVs with the three methods, although significantly higher yields were obtained with UF-precipitation. Dynamic light scattering analysis confirmed the presence of nano-sized particles, being UC-isolated EVs larger than those isolated by UF-precipitation and UF-SEC. Atomic Force Microscopy showed EVs with a slightly ellipsoidal morphology. EVs enriched with UF-precipitation method were further analyzed, confirming the expression of Alix, CD63, TSG101, and Syntenin-1 by Western blotting and showing that Conj-MSC-derived EVs significantly reduced oxidative stress on IM-HConEpiC. Therefore, we conclude that UF-precipitation is the most efficient method for conjunctival EV enrichment.

We have conducted an entropy analysis in Alaska, a seismic-rich region in a subduction zone that exhibits a nontrivial behavior: the subduction arc alters the seismic activity from the eastern zone to the western zone, demonstrating a decrease in activity along the subduction. We analyze this zone through the Tsallis entropy and the mutability (or dynamic entropy) for the first time. Considering 13 870 seismic events after appropriate filtering, we analyzed a data set for the selected Alaska zone between 2000 and 2023. We have found agreement between the results for the two entropies. We have followed the value of the q parameter of the Tsallis entropy (Sq) finding values between 1.70 and 1.85, in concordance with values found in other seismic regions of the planet. The values of Sq decrease slightly over time but show a broad increase before the major earthquakes. Just opposite to Tsallis entropy, mutability shows a tendency to decrease prior to the major earthquakes. We used the simpler mutability method to further analyze this zone upon dividing the region into four subzones. The results show how mutability can identify the seismic activity in each zone. This study shows how an entropy approach can shed light on understanding the seismicity in subduction zones.

Durante el proceso de coagulación dentro de una planta de tratamiento de agua potable (PTAP), para disminuir la turbiedad se usan polímeros sintéticos y orgánicos. La Moringa oleifera (MO), como coagulante natural, requiere usar una concentración y dosis óptima, a fin de reducir la mayor cantidad de turbiedad y evitar materia orgánica residual que requiera un tratamiento adicional. Es por ello que la investigación tuvo como objetivo determinar la eficiencia del uso de la MO, para la clarificación del agua de la quebrada Taczanapampa de la ciudad de Huancavelica, Perú. Se utilizaron las partículas molidas de las semillas de la mencionada planta, evaluando diferentes dosis y concentraciones para encontrar la óptima en la remoción de la turbidez en el agua, procedimiento que se realizó con la prueba de jarras del laboratorio. Los modelos de regresión validaron el comportamiento de la MO en ecuaciones. El primer modelo determinó la dosis óptima y el segundo modelo la concentración óptima en las condiciones de la investigación. Los resultados de la dosis óptima se obtuvieron en dos rangos: con turbiedades menores a 50 unidad nefelométrica de turbidez (UNT) de 10 a 50 mg/l, también entre 50 y 150 UNT de 30 a 100 mg/l; y la concentración óptima para turbiedades menores a 150 UNT se encuentran en un rango de 2 a 3 %. Los resultados se consideran favorables para su uso y amigables con el ambiente.

Dielectric resonator antennas have been demonstrated to be an efficient radiator, especially with the possibility of fabricating it at low cost based on 3-D printing technologies. However, they have two main limitations which are: their relatively small gain (about 5dBi) and narrow bandwidth. To enhance the gain of DRA, higher-order mode excitation can be utilized; however, typically this has a limit of a few dB increments besides its negative effects on the bandwidth. This study employs a cavity-backed slot to provide an appropriate feeding method for a cylindrical dielectric resonator antenna (CDRA). This design effectively facilitates the excitation of higher-order modes, resulting in a significant gain of up to 15 dBi, which is essential for many wireless systems that are unable to support larger aperture sizes through the standard use of arrays. Additionally, two modes are excited to keep a relatively broadband of about 15 %. The proposed design consists of a cylindrical dielectric placed on top of a cavity-backed slot that is excited by a coaxial probe soldered to the top patch of the cavity. With this feeding, a good matching is achieved for different dielectric resonator heights, hence, the gain can be adjusted easily without the need of reoptimizing the antenna or the feed structures. The design process is explained in addition to performing a sensitivity analysis of fabrication tolerances which confirms that the 3-D printer provides enough accuracy with a negligible effect on the antenna’s performance. Then a prototype with a medium length is fabricated and measured to provide high realized gain and impedance bandwidth of 11 dBi and 14.5 %, respectively. The measured data demonstrate the good performance of the antenna with great matching compared to the simulated ones. Furthermore, the antenna presents a good performance in terms of sidelobes and polarization. This proposed design outperforms other DRA designs based on higher-order modes.

Research and innovation are highlighted as significant priorities among Higher Education Institutions (HEIs) in the Philippines. However, most HEIs in the country have a poor culture of research and innovation, which results in low academic productivity. This literature review was conducted to understand the dynamics of a teaching, research, and innovative university, discuss the current status of Philippine HEIs in terms of research (R&D)-innovation productivity, and excerpt best practices from leading universities in the country as a benchmark for other higher institutions toward building a culture of research and innovation. This study highlights different viewpoints but reveals one thing in common among the established research universities: they have exemplary administrative leadership and proper institutional framework, with strong qualifications from their faculty to absorb all the resources pouring in, thereby significantly boosting them and yielding a fruitful result in terms of research and innovation. With these, other Philippines HEIs need to build and develop a vital research and innovative culture among their stakeholders to produce tangible outcomes, which can be utilized for industry-related improvements and new market opportunities, and to address the nation's most pressing issues. Without the support and proper compensation within academia, industry, and government, the pool of talents will be put on the shelf. Nevertheless, leveling up from teaching institutions to become a research and innovative academia remains interesting as it depends primarily on the university's vision and actions, which are mostly affected by its internal and external environment. This paper hopes to be a springboard in formulating policy and practice toward enhancing research and innovation efficiency among the Philippine HEI's that could contribute to the overall nationwide progress.

Abstract Taxonomic classification is crucial in identifying organisms within diverse microbial communities when using metagenomics shotgun sequencing. While second-generation Illumina sequencing still dominates, third-generation nanopore sequencing promises improved classification through longer reads. However, extensive benchmarking studies on nanopore data are lacking. We systematically evaluated performance of bacterial taxonomic classification for metagenomics nanopore sequencing data for several commonly used classifiers, using standardized reference sequence databases, on the largest collection of publicly available data for defined mock communities thus far (nine samples), representing different research domains and application scopes. Our results categorize classifiers into three categories: low precision/high recall; medium precision/medium recall, and high precision/medium recall. Most fall into the first group, although precision can be improved without excessively penalizing recall with suitable abundance filtering. No definitive ‘best’ classifier emerges, and classifier selection depends on application scope and practical requirements. Although few classifiers designed for long reads exist, they generally exhibit better performance. Our comprehensive benchmarking provides concrete recommendations, supported by publicly available code for reassessment and fine-tuning by other scientists.

Abstract Background The high-density lipoprotein cholesterol to apolipoprotein A-I index (HDL-C/ApoA-I) may be practical and useful in clinical practice as a marker of atherosclerosis. This study aimed to investigate the association between the HDL-C/ApoA-I index with cardiometabolic risk factors and subclinical atherosclerosis. Methods In this cross-sectional sub-analysis of the GEA study, 1,363 individuals, women (51.3%) and men (48.7%) between 20 and 75 years old, without coronary heart disease or diabetes mellitus were included. We defined an adverse cardiometabolic profile as excess adipose tissue metrics, non-alcoholic liver fat measured by non-contrasted tomography, metabolic syndrome, dyslipidemias, and insulin resistance. The population was stratified by quartiles of the HDL-C/Apo-AI index, and its dose-relationship associations were analysed using Tobit regression, binomial, and multinomial logistic regression analysis. Results Body mass index, visceral and pericardial fat, metabolic syndrome, fatty liver, high blood pressure, and CAC were inversely associated with the HDL-C/ApoA-I index. The CAC > 0 prevalence was higher in quartile 1 (29.2%) than in the last quartile (22%) of HDL-C/ApoA-I index (p = 0.035). The probability of having CAC > 0 was higher when the HDL-C/ApoA-I index was less than 0.28 (p

The purple non-sulfur bacterium Rhodopseudomonas palustris is recognized as a critical microorganism in the nitrogen and carbon cycle and one of the most common members in wastewater treatment communities. This bacterium is metabolically extremely versatile. It is capable of heterotrophic growth under aerobic and anaerobic conditions, but also able to grow photoautotrophically as well as mixotrophically. Therefore R. palustris can adapt to multiple environments and establish commensal relationships with other organisms, expressing various enzymes supporting degradation of amino acids, carbohydrates, nucleotides, and complex polymers. Moreover, R. palustris can degrade a wide range of pollutants under anaerobic conditions, e.g., aromatic compounds such as benzoate and caffeate, enabling it to thrive in chemically contaminated environments. However, many metabolic mechanisms employed by R. palustris to breakdown and assimilate different carbon and nitrogen sources under chemoheterotrophic or photoheterotrophic conditions remain unknown. Systems biology approaches, such as metabolic modeling, have been employed extensively to unravel complex mechanisms of metabolism. Previously, metabolic models have been reconstructed to study selected capabilities of R. palustris under limited experimental conditions. Here, we developed a comprehensive metabolic model (M-model) for R. palustris Bis A53 (iDT1294) consisting of 2,721 reactions, 2,123 metabolites, and comprising 1,294 genes. We validated the model using high-throughput phenotypic, physiological, and kinetic data, testing over 350 growth conditions. iDT1294 achieved a prediction accuracy of 90% for growth with various carbon and nitrogen sources and close to 80% for assimilation of aromatic compounds. Moreover, the M-model accurately predicts dynamic changes of growth and substrate consumption rates over time under nine chemoheterotrophic conditions and demonstrated high precision in predicting metabolic changes between photoheterotrophic and photoautotrophic conditions. This comprehensive M-model will help to elucidate metabolic processes associated with the assimilation of multiple carbon and nitrogen sources, anoxygenic photosynthesis, aromatic compound degradation, as well as production of molecular hydrogen and polyhydroxybutyrate.

Liver metastasis is a major cause of death in patients with colorectal cancer (CRC). Fatty liver promotes liver metastasis, but the underlying mechanism remains unclear. We demonstrated that hepatocyte-derived extracellular vesicles (EVs) in fatty liver enhanced the progression of CRC liver metastasis by promoting oncogenic Yes-associated protein (YAP) signaling and an immunosuppressive microenvironment. Fatty liver upregulated Rab27a expression, which facilitated EV production from hepatocytes. In the liver, these EVs transferred YAP signaling-regulating microRNAs to cancer cells to augment YAP activity by suppressing LATS2. Increased YAP activity in CRC liver metastasis with fatty liver promoted cancer cell growth and an immunosuppressive microenvironment by M2 macrophage infiltration through CYR61 production. Patients with CRC liver metastasis and fatty liver had elevated nuclear YAP expression, CYR61 expression, and M2 macrophage infiltration. Our data indicate that fatty liver-induced EV-microRNAs, YAP signaling, and an immunosuppressive microenvironment promote the growth of CRC liver metastasis.

ObjectivesAscites, often associated with critical pathologies such as liver cirrhosis or bowel perforation, can be complicated by fungal infection, increasing mortality especially in intensive care settings and demanding rapid diagnosis and adequate treatment. Traditional microbiological diagnostic methods have limited sensitivity in accurately identifying fungal pathogens in ascitic fluid. Alternative diagnostic methods may offer important insights to enable guiding of antifungal therapy and refining empirical treatment strategies. The objective of this study was to evaluate the potential of next-generation sequencing methods to identify specific fungal pathogens responsible for ascitic fluid infections.MethodsWe prospectively collected 50 ascitic fluid samples from ICU patients with suspected ascites infection. In addition to standard culture-based microbiological testing, an ascitic fluid aliquot underwent fungal DNA isolation and was analyzed by next-generation sequencing (NGS) methods for identification of fungal species.ResultsOf 50 ascitic samples collected, five samples showed growth of Candida spp. in culture. After DNA isolation and ITS2 PCR, detectable amplification was achieved in 10 samples. Sequencing of the 50 patients’ samples identified facultative pathogenic fungi in 19 patients. In 15 cases, culture alone would not have permitted the identification of all facultative pathogenic fungi. The identification of fungal DNA by sequencing was significantly associated with poor patient outcome and a number of clinical parameters.ConclusionsOur results show a higher sensitivity for NGS-based diagnostic methods in the identification of ascitic fluid fungal infections compared to culture-based diagnostics. This may be beneficial especially for patients in a critical care setting, who have an increased prevalence of comorbidities and high mortality. The implementation of such methods in standard diagnosis will require increased standardization of the workflows and interpretation of the sequencing results with respect to patients’ clinical picture.

BackgroundThe outcome disparities for African American recipients of kidney transplant is a public health issue that has plagued the field of transplant since its inception. Based on national data, African American recipients have nearly twice the risk of graft loss at 5 years after transplant, when compared with White recipients. Evidence demonstrates that medication nonadherence and high tacrolimus variability substantially impact graft outcomes and racial disparities, most notably late (>2 years) after the transplant. Nonadherence is a leading cause of graft loss. Prospective multicenter data demonstrate that one-third of all graft loss are directly attributed to nonadherence. We have spent 10 years of focused research to develop a comprehensive model explaining the predominant risk factors leading to disparities in African American kidney recipients. However, there are still gaps in patient-level data that hinder the deeper understanding of the disparities. Lack of data from the patient often lead to provider biases, which will be addressed with this intervention. Culturally competent, pharmacist-led interventions in medication therapy management will also address therapeutic inertia. Pharmacist interventions will mitigate medication access barriers as well (cost and insurance denials). Thus, this multidimensional intervention addresses patient, provider, and structural factors that drive racial disparities in African American kidney recipients. ObjectiveThis prospective, randomized controlled trial aimed to determine the impact of multimodal health services intervention on health outcomes disparities in African American recipients of kidney transplant. The aims of this study are to improve adherence and control of late clinical issues, which are predominant factors for racial disparities in kidney recipients, through a technology-enabled, telehealth-delivered, 4-level intervention. MethodsThe Multifaceted Intervention to Improve Graft Outcome Disparities in African American Kidney Transplants (MITIGAAT) study is a 24-month, 2-arm, single-center (Medical University of South Carolina), 1:1 randomized controlled trial involving 190 participants (95 in each arm), measuring the impact on adherence and control of late clinical issues for racial disparities in kidney recipients, through a technology-enabled, telehealth-delivered, 4-level intervention. The key clinical issues for this study include tacrolimus variability, blood pressure, and glucose control (in those with diabetes mellitus). We will also assess the impact of the intervention on health care use (hospitalizations and emergency department visits) and conduct a cost-benefit analysis. Finally, we will assess the impact of the intervention on acute rejection and graft survival rates as compared with a large contemporary national cohort. ResultsThis study was funded in July 2023. Enrolled began in April 2024 and is expected to be complete in 2026. All patients will complete the study by the end of 2028. ConclusionsIn this protocol, we describe the study design, methods, aims, and outcome measures that will be used in the ongoing MITIGAAT clinical trials. Trial RegistrationClinicalTrials.gov NCT06023615; https://www.clinicaltrials.gov/study/NCT06023615 International Registered Report Identifier (IRRID)PRR1-10.2196/57784

Derivado del Programa de Seguimiento Institucional de Egresados (PISE), de la Escuela Normal de Valle de Bravo, se presentan resultados parciales de la investigación con el objetivo de identificar las condiciones de empleabilidad de los docentes noveles de las generaciones 2018-2022 y 2019-2023, así como las implicaciones que tiene la asignación de códigos emitidos por la Unidad del Sistema para la Carrera de las Maestras y los Maestros (USICAMM), cuyos hallazgos alertan de un proceso de contratación punitivo que ha generado, entre los normalistas, frustración, incertidumbre, desconfianza, renuncia y un evidente incremento de desempleo.

La investigación se centró en comparar las estrategias usadas por los estudiantes de tres escuelas normales del Estado de México en su último semestre de formación. Se utilizó un enfoque cualitativo y un diseño no experimental de tipo transversal. El objetivo fue comparar las estrategias de enseñanza empleadas durante las prácticas profesionales. La muestra por saturación incluyó a tres docentes y 60 estudiantes. Para la recolección de datos, se utilizó la técnica de la encuesta, cuyos resultados fueron interpretados mediante codificación. Finalmente, se identificaron las estrategias de enseñanza que prefieren los normalistas y cómo el contexto influye en el diseño y la selección.

Searching for positive selection signals across genomes has identified functional genetic variants responding to environmental change. In Native Americans of Mexico, we used the fixation index (Fst) and population branch statistic (PBS) to identify SNPs suggesting positive selection. The 103 most differentiated SNPs were tested for associations with metabolic traits, the most significant association was FADS2/rs174616 with body mass index (BMI). This variant lies within a linkage disequilibrium (LD) block independent of previously reported FADS selection signals and has not been clearly associated with metabolic phenotypes. We tested this variant in two independent cohorts with cardiometabolic data. In the Genetics of Atherosclerotic Disease (GEA) cohort, the derived allele (T) was associated with increased BMI, lower LDL-C levels and a decreased risk of subclinical atherosclerosis in women. Significant gene-diet interactions affected lipid, apolipoprotein and adiponectin levels with differences according to sex, involving mainly total and complex dietary carbohydrate%. In the Genotype-related Effects of PUFA trial, the derived allele was associated with lower Δ-6 desaturase activity and erythrocyte membrane dihomo-gamma-linolenic acid (DGLA) levels, and with increased Δ-5 desaturase activity and eicosapentaenoic acid levels. This variant interacted with dietary carbohydrate% affecting Δ-6 desaturase activity. Notably, the relationship of DGLA and other erythrocyte membrane LC-PUFA indices with HOMA-IR differed according to rs174616 genotype, which has implications regarding how these indices should be interpreted. In conclusion, this observational study identified rs174616 as a signal suggesting selection in an independent linkage disequilibrium block, was associated with cardiometabolic and erythrocyte measurements of LC-PUFA in two independent Mexican cohorts and showed significant gene-diet interactions.