Search Results (24)

Alagille syndrome (ALGS) is a multisystem disorder characterized by a paucity of intrahepatic bile ducts and cholestasis, often requiring liver transplantation before adulthood. Due to the lack of genotype–phenotype correlation, case series are essential to understand disease presentation and prognosis. Data on Mexican ALGS patients are limited. Therefore, we aimed to characterize a large series of Mexican patients by consolidating cases from major institutions and independent geneticists, with the goal of generating one of the most comprehensive cohorts in Latin America. We retrospectively analyzed clinical records of pediatric ALGS patients, focusing on demographics, clinical features, laboratory and imaging results, biopsy findings, and transplant status. Genetic testing was performed for all cases without prior molecular confirmation. We identified 52 ALGS cases over 13 years; 22 had available clinical records. Of these, only 6 had molecular confirmation at study onset, prompting genetic testing in the remaining 16. We identified six novel JAG1 variants and several previously unreported phenotypic features. A liver transplantation rate of 13% was observed in the cohort. This study represents the largest molecularly confirmed ALGS cohort in Mexico to date. Novel genetic and clinical findings expand the known spectrum of ALGS and emphasize the need for improved therapies, such as IBAT inhibitors, which may alleviate symptoms and reduce the need for transplantation. Full article

Background/Objectives: One current cancer treatment is immunotherapy, in which tumor antigens (such as MAGE) or adjuvants (such as CpGs) can be used to induce the destruction of tumor cells by the immune system; however, the therapeutic response is generally weak. Therefore, it is necessary to develop a strategy that increases the immune response induced by tumor antigens and CpGs. We propose the coupling of tumor antigens and adjuvants to chitosan (Cs) microparticles to improve the immune response against cancer, as these microparticles can activate the innate immune response when recognized by macrophages and dendritic cells (DCs). Methods: Cs microparticles coupled with CpGs and tumor antigens were constructed with the emulsification method; then, their morphology, in vitro biological effect on DCs, and therapeutic effect in a murine melanoma model were analyzed. Results: The Cs microparticles showed a rounded morphology and a size of approximately 5 μ; in addition, they were not cytotoxic in in vitro assays and induced the production of IFNα. Finally, in the murine model of melanoma, treatment with Cs microparticles coupled to MAGE or CpGs reduced the tumor growth rate and increased both survival and the presence of cell death areas in the tumor parenchyma in contrast to the control group. Conclusions: The results suggest that treatment with Cs microparticles coupled to tumor antigen and/or CpGs can be considered a promising strategy in the field of immunotherapy based on the use of biomaterials. Full article

Clustering algorithms help handle unlabeled datasets. In large datasets, density-based clustering algorithms effectively capture the intricate structures and varied distributions that these datasets often exhibit. However, while these algorithms can adapt to large datasets by building clusters with arbitrary shapes by identifying low-density regions, they usually struggle to identify density variations. This paper proposes a Variable DEnsity Clustering Algorithm for Large datasets (VDECAL) to address this limitation. VDECAL introduces a large-dataset partitioning strategy that allows working with manageable subsets and prevents workload imbalance. Within each partition, relevant objects subsets characterized by attributes such as density, position, and overlap ratio are computed to identify both low-density regions and density variations, thereby facilitating the building of the clusters. Extensive experiments on diverse datasets show that VDECAL effectively detects density variations, improving clustering quality and runtime performance compared to state-of-the-art DBSCAN-based algorithms developed for clustering large datasets. Full article

Optimized in vitro cultivation offers a sustainable solution to enhance blackberry (Rubus spp.) production while reducing pathogen contamination during propagation. This study developed and validated protocols for in vitro cultivation and ex vitro acclimatization of the Tupy, Brazos, and Kiowa cultivars at the Instituto Tecnológico Superior de Los Reyes, Michoacán. A 20 min treatment with 2% sodium hypochlorite (NaOCl) reduced contamination by below 10% and achieved explant survival rates exceeding 95%. Temporary Immersion Systems (TIS) with four to six immersion cycles of 5 min each maximized survival (above 95%) while minimizing necrosis and hyperhydricity and increasing fresh mass. Shoot development was significantly enhanced with 2 mg L⁻¹ 6-benzylaminopurine, and 1 mg L⁻¹ indole-3-butyric acid promoted optimal root formation. Acclimatization success rates exceeded 90% in covered trays compared to significant losses in uncovered trays during early stages. These protocols enabled robust plant development and yields exceeding 10 t ha ⁻¹ during vegetative and reproductive stages, providing a scalable framework for sustainable blackberry production and broader applications in crop propagation. Full article

The development of immune checkpoint inhibitors (ICIs) has changed the therapeutic paradigm of lung cancer (LC), becoming the standard of treatment for previously untreated advanced non-small cell lung cancer (NSCLC) without actionable mutations. It has allowed the achievement of durable responses and resulted in significant survival benefits. However, not all patients respond; hence, molecular biomarkers are needed to help us predict which patients will respond. With this objective, a prospective observational study was designed, including a cohort of 55 patients with NSCLC who received ICIs. We studied whether biomarkers such as TCRβ and specific cytokines involved in the regulation of T cell activity were related to the immunotherapy response. In the survival analysis, it was found that patients with higher TCRβ clonality, lower TCRβ evenness, higher TCRβ Shannon diversity and lower TCRβ convergence had higher overall survival (OS) and progression-free survival (PFS). However, no statistically significant association was observed. Regarding cytokines, those patients with higher levels of IL-2 and IL-15 presented statistically significantly shorter OS and PFS, respectively. In fact, in the multivariable analysis, the high IL-15 level increased the risk of death by three times. Although the sample size was small and more studies are needed to confirm our results, our study reveals promising markers of responses to ICIs. Full article

Immune checkpoint inhibitors have been proposed as the standard treatment for different stages of non-small-cell lung cancer in multiple indications. Not all patients benefit from these treatments, however, and certain patients develop immune-related adverse events. Although the search for predictors of response to these drugs is a major field of research, these issues have yet to be resolved. It has been postulated that microbiota could play a relevant role in conditioning the response to cancer treatments; however, the human factor of intestinal permeability also needs to be considered as it is closely related to the regulation of host–microbiota interaction. In this article, we analyzed the possible relationship between the response to immune checkpoint inhibitors and the onset of immune-related adverse events, gut microbiota status, and intestinal membrane permeability. In a pioneering step, we also measured short-chain fatty acid content in feces. Although the correlation analyses failed to identify predictive biomarkers, even when all variables were integrated, our patients’ microbial gut ecosystems were rich and diverse, and the intestinal barrier’s integrity was preserved. These results add new knowledge on the composition of microbiota and its correlation with barrier permeability and short-chain fatty acids and suggest that more studies are required before these potential biomarkers can be incorporated into the clinical management of patients via immune checkpoint inhibitor treatment. Full article

Myxoid endometriosis, a rare entity, is part of the histological changes that can occur in endometriosis. Pathologists must know the histological guidelines for the morphological recognition of this entity, as well as the histochemical and immunohistochemical techniques that support diagnosis, and define the morphological characteristics of myxoid endometriosis. In the present work, we propose diagnostic guidelines and primary differential diagnoses using special histochemical techniques and immunohistochemical reactions to recognize this entity. Full article

Lignocellulosic materials are usually processed toward C5 and C6 corresponding sugars. Trifluoroacetic acid (TFA) is a pretreatment method to solubilize hemicellulose to sugars such xylose without degrading cellulose. However, this pretreatment has not been compared to other processes. Thus, this paper focuses on the techno-economic comparison of the C5–C6 production of C5–C6 as raw materials platforms using non-centrifuged sugarcane bagasse (NCSB) and Pinus patula wood chips (PP). Hydrolysates using TFA 2.5 M as an acid were characterized through HPLC regarding arabinose, galactose glucose, xylose, and mannose sugars. Then, simulations of the processes according to the experimental results were done. The economic assessment was performed, and compared with some common pretreatments. The mass and energy balances of the simulations indicate that the process can be compared with other pretreatments. From the economic perspective, the main operating expenditures (OpEx) are related to raw materials and capital depreciation due to the cost of TFA corrosion issues. The processes showed a CapEx and OpEx of 0.99 MUSD and 6.59 M-USD/year for NCSB, and 0.97 MUSD and 4.37 MUSD/year for PP, considering a small-scale base (1 ton/h). TFA pretreatment is innovative and promising from a techno-economic perspective. Full article

We derive the governing equations for the overall behaviour of linear viscoelastic composites comprising two families of elastic inclusions, subphases and/or fibres, and an incompressible Newtonian fluid interacting with the solid phases at the microscale. We assume that the distance between each of the subphases is very small in comparison to the length of the whole material (the macroscale). We can exploit this sharp scale separation and apply the asymptotic (periodic) homogenization method (AHM) which decouples spatial scales and leads to the derivation of the new homogenised model. It does this via upscaling the fluid–structure interaction problem that arises between the multiple elastic phases and the fluid. As we do not assume that the fluid flow is characterised by a parabolic profile, the new macroscale model, which consists of partial differential equations, is of Kelvin–Voigt viscoelastic type (rather than poroelastic). The novel model has coefficients that encode the properties of the microstructure and are to be computed by solving a single local differential fluid–structure interaction (FSI) problem where the solid and the fluid phases are all present and described by the one problem. The model reduces to the case described by Burridge and Keller (1981) when there is only one elastic phase in contact with the fluid. This model is applicable when the distance between adjacent phases is smaller than the average radius of the fluid flowing in the pores, which can be the case for various highly heterogeneous systems encountered in real-world (e.g., biological, or geological) scenarios of interest. Full article

We develop a general approach for the computation of the effective properties of nonlinear viscoelastic composites. For this purpose, we employ the asymptotic homogenisation technique to decouple the equilibrium equation into a set of local problems. The theoretical framework is then specialised to the case of a strain energy density of the Saint-Venant type, with the second Piola–Kirchhoff stress tensor also featuring a memory contribution. Within this setting, we frame our mathematical model in the case of infinitesimal displacements and employ the correspondence principle which results from the use of the Laplace transform. In doing this, we obtain the classical cell problems in asymptotic homogenisation theory for linear viscoelastic composites and look for analytical solutions of the associated anti-plane cell problems for fibre-reinforced composites. Finally, we compute the effective coefficients by specifying different types of constitutive laws for the memory terms and compare our results with available data in the scientific literature. Full article

Food losses (FL) and waste (FW) occur throughout the food supply chain. These residues are disposed of on landfills producing environmental issues due to pollutants released into the air, water, and soil. Several research efforts have focused on upgrading FL and FW in a portfolio of added-value products and energy vectors. Among the most relevant research advances, biotechnological upgrading of these residues via fermentation has been demonstrated to be a potential valorization alternative. Despite the multiple investigations performed on the conversion of FL and FW, a lack of comprehensive and systematic literature reviews evaluating the potential of fermentative processes to upgrade different food residues has been identified. Therefore, this article reviews the use of FL and FW in fermentative processes considering the composition, operating conditions, platforms, fermentation product application, and restrictions. This review provides the framework of food residue fermentation based on reported applications, experimental, and theoretical data. Moreover, this review provides future research ideas based on the analyzed information. Thus, potential applications and restrictions of the FL and FW used for fermentative processes are highlighted. In the end, food residues fermentation must be considered a mandatory step toward waste minimization, a circular economy, and the development of more sustainable production and consumption patterns. Full article

(1) Despite the effectiveness of immune checkpoint inhibitors (ICIs) in lung cancer, there is a lack of knowledge about predictive biomarkers. The objective of our study is to analyze different subsets of T-lymphocytes and natural killer (NK) cells as predictive biomarkers in a cohort of patients with nonsmall cell lung cancer (NSCLC) treated with ICI. (2) This is an observational, prospective study with 55 NSCLC patients treated with ICI. A total of 43 T and NK cell subsets are analyzed in peripheral blood, including the main markers of exhaustion, differentiation, memory, activation, and inhibition. (3) Regarding the descriptive data, Granzyme B+CD4+ Treg lymphocytes stand out (median 17.4%), and within the NK populations, most patients presented cytotoxic NK cells (CD56+CD3−CD16+GranzymeB+; median 94.8%), and about half of them have highly differentiated adaptive-like NK cells (CD56+CD3−CD16+CD57+ (mean 59.8%). A statistically significant difference was observed between the expression of PD1 within the CD56^bright NK cell subpopulation (CD56+CD3−CD16−PD-1+) (p = 0.047) and a better OS. (4) Circulating immune cell subpopulations are promising prognostic biomarkers for ICI. Pending on validation with a larger sample, here we provide an analysis of the major circulating T and NK cell subsets involved in cancer immunity, with promising results despite a small sample size. Full article

At least 59 maize races (Zea mays L.) have been registered in Mexico. The feeding damage caused by insects and mites to maize crops generates up to ~30% of maize yield losses. Spider-mite-resistant plants are needed. The red spider mite, Tetranychus merganser Boudreaux (Acari: Tetranychidae), is distributed in the United States, China, Mexico, and Thailand. It is considered a potential pest in Mexican agriculture. The aim of this study was to evaluate the resistance mechanisms (antixenosis and antibiosis) of 11 native maize populations, representative of each race of maize grown in Tamaulipas, Mexico, to T. merganser under laboratory conditions. The aim was also to obtain information on the chemical composition and some morphological characteristics of these maize races and to identify resistant maize races for incorporation into a breeding program. Antixenosis was assessed by non-preference for oviposition and feeding. Antibiosis was measured by growth rate (ri). The presence of secondary metabolites in the 11 maize races were different. In the 11 maize races, quantitative analysis of total phenol concentration, total flavonoid concentration, and antioxidant capacity were significantly different. The multivariate analysis of variance showed that there is evidence of antixenosis noted by maize race differences in egg laying and percentage feeding damage but not of antibiosis noted by growth rate. Red spider mites laid significantly more eggs on the Celaya (24 h: 25.67 ± 17.04, 48 h: 42.67 ± 26.86, 72 h: 49.33 ± 28.54) race than on Raton (24 h: 7.00 ± 5.00, 48 h: 12.67 ± 8.02, 72 h: 14.67 ± 9.29) and Elotes Occidentales × Tuxpeño (24 h: 9.67 ± 5.85, 48 h: 15.33 ± 10.69, 72 h: 17.67 ± 10.97) races. However, the growth rate and mortality of T. merganser in the 11 corn races were similar. The Vandeño (24 h: 11.67 ± 2.89, 48 h: 27.67 ± 7.64, 72 h: 30.00 ± 18.03) and Tabloncillo × Tuxpeño (24 h: 18.33 ± 7.64, 48 h: 25.00 ± 8.66, 72 h: 25.00 ± 8.66) races were the most resistant to red spider mite damage, whereas the most susceptible race was Celaya (24 h: 26.67 ± 15.28, 48 h: 48.33 ± 29.30, 72 h: 65.00 ± 30.00). Further analysis by PCA at 24, 48, and 72 h found the Celaya race positively correlated to growth rate and oviposition of T. merganser and to a lesser extent with the percentage of feeding damage, suggesting that the Celaya race was most susceptible to T. merganser. At 24 h, the Vandeño race was most resistant, given a negative correlation to growth rate and oviposition by T. merganser. The PCA at 48 and 72 h noted the Elotes Occidentales × Tuxpeño race was most resistant to red spider mite, with negative relationships to growth rate and oviposition and, to a lesser extent, to feeding damage. This resistance is due to the differences in both its morphological characteristics and the secondary metabolites present in their leaves. Full article

Gliotoxin is a fungal secondary metabolite with impact on health and agriculture since it might act as virulence factor and contaminate human and animal food. Homologous gliotoxin (GT) gene clusters are spread across a number of fungal species although if they produce GT or other related epipolythiodioxopiperazines (ETPs) remains obscure. Using bioinformatic tools, we have identified homologous gli gene clusters similar to the A. fumigatus GT gene cluster in several fungal species. In silico study led to in vitro confirmation of GT and Bisdethiobis(methylthio)gliotoxin (bmGT) production in fungal strain cultures by HPLC detection. Despite we selected most similar homologous gli gene cluster in 20 different species, GT and bmGT were only detected in section Fumigati species and in a Trichoderma virens Q strain. Our results suggest that in silico gli homology analyses in different fungal strains to predict GT production might be only informative when accompanied by analysis about mycotoxin production in cell cultures. Full article

The Misa Criolla by Ariel Ramirez is a symbol of liberation theology in South America. Written between 1963–1964, this musical work is the result of the decisions made on the sacred liturgy at Vatican II and the Indigenous Movements of the 1960s and 1970s. It became popular around the world and helped bring attention to the indigenous poor of South America through its indigenization of the Roman Catholic Mass text and music directly after the Second Vatican Council. The Misa Criolla, however, can only be fully appreciated by understanding its process of localization, from its historical context, theological underpinnings to its musical attributes. From a liberationist perspective, it represents the compromise of the openness, liturgically and theologically, of Vatican II and more conservative movements afterwards through the localization of the Catholic Mass liturgy. Full article