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Abstract Microalgae like Chlamydomonas are beneficial organisms employed as biological stimulants to improve plants’ growth, fruit quality, and stress tolerance. In the current study, the effects of Chlamydomonas sp. foliar spraying (0, 20, and 40 ml L−1) were assayed on Camarosa strawberry plants under salinity stress (0, 40, and 80 mM NaCl). The results showed that the foliar application of Chlamydomonas extract influenced strawberry’s morphological, physiological, and biochemical characteristics under salinity stress. Foliar treatment of Chlamydomonas extract with and without salinity stress increased the leaf number and leaf area, the leaf relative water content, and photosynthetic pigments content. Moreover, the foliar application of Chlamydomonas extract decreased lipid peroxidation and hydrogen peroxide content and, on the other hand, enhanced the antioxidant enzymes activity (superoxide dismutase, guaiacol peroxidase, and peroxidase), phenolics, flavonoids, and anthocyanins content under salinity stress. For instance, the highest total antioxidant capacity was found in the plants foliar treated with 40 ml L−1 of Chlamydomonas algae extract under 80 mM salinity stress, which increased by 102.4% compared to the controls, as well as the highest total phenolic compounds and anthocyanin’s content were 30.22, and 7.2% more than the control plants, respectively. Overall, the foliar application of Chlamydomonas algae extracts, especially at a concentration of 20 ml L−1 enhanced the strawberry’s growth, yield, and physiological traits under saline conditions. The results with more detailed evaluations will be advisable for the pioneer farmers and extension section.

Abstract At the molecular level, triple-negative breast cancer (TNBC) is frequently categorized as PAM50 basal-like subtype, but despite the advances in molecular analyses, the clinical outcome for these subtypes is uncertain. Long non-coding RNAs (lncRNAs) are master regulators of genes involved in hallmarks of cancer, which makes them suitable biomarkers for breast cancer (BRCA) diagnosis and prognosis. Here, we evaluated the regulatory role of lncRNA SOX9-AS1 in these subtypes. Using the BRCA-TCGA cohort, we observed that SOX9-AS1 was significantly overexpressed in basal-like and TNBC in comparison with other BRCA subtypes. Survival analyzes showed that SOX9-AS1 overexpression was associated with a favorable prognosis in TNBC and basal-like patients. To study the functions of SOX9-AS1, we determined the expression levels in a panel of nine BRCA cell lines finding increased levels in MDA-MB-468 and HCC1187 TNBC. Using subcellular fractionation in these cell lines, we ascertained that SOX9-AS1 was located in the cytoplasmic compartment. In addition, we performed SOX9-AS1 gene silencing using two short-harping constructs, which were transfected in both cell models and performed a genome-wide RNA-seq analysis. Data showed that 351 lncRNAs and 740 mRNAs were differentially expressed in MDA-MB-468 while 56 lncRNAs and 100 mRNAs were modulated in HCC1187 cells (Log2FC 1.5, p.adj value

Abstract Rationale In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. Aims To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. Sample size estimates Two hundred forty patients will be enrolled, 120 in every treatment arm. Methods and design A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. Study outcomes Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. Discussion This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. Trial registration The trial is registered as NCT05225961. February, 7th, 2022.

En el 2008, el nivel educativo medio superior mexicano fue objeto de una reforma educativa que buscó asentar un modelo curricular basado en competencias. Para lograr lo anterior, se consideró central el cambio de las prácticas de enseñanza de los docentes. Desde una perspectiva estructural constructivista, se usó el concepto de habitus académico para realizar una aproximación sobre los cambios y persistencias en las prácticas de enseñanza comúnmente empleadas por los docentes, y la manera en cómo estas son percibidas por los estudiantes. Por medio del Paquete Estadístico para las Ciencias Sociales (SPSS por sus siglas en inglés), se empleó el cálculo de medias, además de pruebas de correlación para el procesamiento de la información procedente de 1033 estudiantes de recién ingreso —en el 2018— a trece facultades de la Universidad Veracruzana. Se presentan los resultados en dos secciones analíticas, exposición e incorporación. En la primera se detalla que la mayoría de los estudiantes fueron expuestos a prácticas educativas de tipo tradicional. En la segunda se describe la relación de esas prácticas con la forma en que los estudiantes clasifican y jerarquizan las prácticas de enseñanza. Considerando la información expuesta, se discuten los resultados tratando de dar cuenta tanto de los cambios como de las persistencias del habitus en el bachillerato. Se identifica una relación positiva entre el uso frecuente de prácticas de instrucción y de evaluación, con la forma en que los estudiantes clasificaban y jerarquizaban valorativamente las prácticas educativas.

BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.MethodsA total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.ResultsWe identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed.DiscussionOur findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome.

Cell models are indispensable tools in biotechnology when investigating the functional properties of organic compounds. The emergence of various additives designed to enhance animal production has introduced the need for in-depth evaluations, which are often hindered by the complexities of in vivo testing. In this study, we harnessed cell-based models to scrutinize the impact of Solergy as a regulator of cellular metabolism with a particular focus on its modulation of glycogen and antioxidant effects. Our experiment was designed to include assessments of the influence of Solergy on the viability of both terrestrial and aquatic vertebrate cell models, which revealed the benign nature of Solergy and its lack of adverse effects. Furthermore, we examined the capacity of Solergy to modulate intracellular ATP concentrations and enhance glycogen accumulation. Notably, the antioxidant potential of Solergy and its ability to mitigate cellular aging were evaluated within the same cellular frameworks. The outcomes of our investigation suggest that Solergy is a potent metabolic regulator that elevates cellular activity while exerting an antioxidant effect. Importantly, our study demonstrates that Solergy does not induce changes in membrane oxidation. These findings indicate the potential of using Solergy to regulate glycogen synthesis, intracellular ATP concentrations, and oxidative stress in production animals. The multifaceted effects of this additive, which acts as both a metabolism enhancer and an antioxidant, open doors to the creation of custom diets tailored to meet specific production needs while maintaining stable production parameters.

The utilization of treated wastewater can enhance the crops’ irrigation efficacy by offering an extra source of water and nutrients for agricultural purposes. This methodology helps alleviate the pressure on conventional water resources and can be a sustainable strategy to address the challenges of water scarcity. However, it is essential to ensure that wastewater is properly treated to meet quality and safety standards before its application to agricultural crops. This study focuses on exploring the reuse of wastewater from microalgae production and its impact on Pelargonium × hortorum growth during two seasons (autumn and spring). The established treatments were as follows: tap water (control 1); 100% IW—inlet wastewater (control 2); 100% OW—outlet from the reactor; 75% OW + 25% W—75% outlet from the reactor and 25% tap water; and 50% OW + 50%W—50% outlet from the reactor and 50% tap water. Irrigation with wastewater in autumn did not have a significant negative effect (p > 0.05) on plant height, plant diameter, leaf dry weight, roots, or total dry weight, and it was comparable to the control in all applied percentages. On the other hand, wastewater irrigation during spring had a meaningful positive (p < 0.05) impact on plant growth compared to the control. These wastewater resources have a high concentration of nutrients, making them a valuable source of essential and/or beneficial elements. The levels of nutrients such as NO3− range from 144.08 ppm to 82.10 ppm, PO43− ranges from 14.14 ppm to 7.11 ppm, and K+ ranges from 36.83 ppm to 29.71 ppm. Therefore, the obtained results support the viability and effectiveness of using wastewater after microalgae production in agriculture to reduce water demand, mitigate water pollution, and substitute chemical fertilizer input, contributing to more sustainable agricultural practices. These results, with more detailed evaluations, would be applicable to other related plant species and are even applicable to the commercial production sectors.

IntroductionAcute leukemias (AL) are the main types of cancer in children worldwide. In Mexico, they represent one of the main causes of death in children under 20 years of age. Most of the studies on the incidence of AL in Mexico have been developed in the urban context of Greater Mexico City and no previous studies have been conducted in the central-south of the country through a population-based study. The aim of the present work was to identify the general and specific incidence rates of pediatric AL in three states of the south-central region of Mexico considered as some of the marginalized populations of Mexico (Puebla, Tlaxcala, and Oaxaca).MethodsA population-based study was conducted. Children aged less than 20 years, resident in these states, and newly diagnosed with AL in public/private hospitals during the period 2021-2022 were identified. Crude incidence rates (cIR), standardized incidence rates (ASIRw), and incidence rates by state subregions (ASIRsr) were calculated. Rates were calculated using the direct and indirect method and reported per million children under 20 years of age. In addition, specific rates were calculated by age group, sex, leukemia subtype, and immunophenotype.ResultsA total of 388 cases with AL were registered. In the three states, the ASIRw for AL was 51.5 cases per million (0-14 years); in Puebla, it was 53.2, Tlaxcala 54.7, and Oaxaca de 47.7. In the age group between 0-19 years, the ASIRw were 44.3, 46.4, 48.2, and 49.6, in Puebla, Tlaxcala, and Oaxaca, respectively. B-cell acute lymphoblastic leukemia was the most common subtype across the three states.ConclusionThe incidence of childhood AL in the central-south region of Mexico is within the range of rates reported in other populations of Latin American origin. Two incidence peaks were identified for lymphoblastic and myeloid leukemias. In addition, differences in the incidence of the disease were observed among state subregions which could be attributed to social factors linked to the ethnic origin of the inhabitants. Nonetheless, this hypothesis requires further investigation.

BackgroundA heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC).MethodsA population-based case-control study was conducted. Children

BackgroundAdvances in the understanding of the pathobiology of childhood B-cell acute lymphoblastic leukemia (B-ALL) have led towards risk-oriented treatment regimens and markedly improved survival rates. However, treatment-related toxicities remain a major cause of mortality in developing countries. One of the most common adverse effects of chemotherapy in B-ALL is the hematologic toxicity, which may be related to genetic variants in membrane transporters that are critical for drug absorption, distribution, and elimination. In this study we detected genetic variants present in a selected group genes of the ABC and SLC families that are associated with the risk of high-grade hematologic adverse events due to chemotherapy treatment in a group of Mexican children with B-ALL.MethodsNext generation sequencing (NGS) was used to screen six genes of the ABC and seven genes of the SLC transporter families, in a cohort of 96 children with B-ALL. The grade of hematologic toxicity was classified according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, Subsequently, two groups of patients were formed: the null/low-grade (grades 1 and 2) and the high-grade (grades 3 to 5) adverse events groups. To determine whether there is an association between the genetic variants and high-grade hematologic adverse events, logistic regression analyses were performed using co-dominant, dominant, recessive, overdominant and log-additive inheritance models. Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated.ResultsWe found two types of associations among the genetic variants identified as possible predictor factors of hematologic toxicity. One group of variants associated with high-grade toxicity risk: ABCC1 rs129081; ABCC4 rs227409; ABCC5 rs939338, rs1132776, rs3749442, rs4148575, rs4148579 and rs4148580; and another group of protective variants that includes ABCC1 rs212087 and rs212090; SLC22A6 rs4149170, rs4149171 and rs955434.ConclusionThere are genetic variants in the SLC and ABC transporter families present in Mexican children with B-ALL that can be considered as potential risk markers for hematologic toxicity secondary to chemotherapeutic treatment, as well as other protective variants that may be useful in addition to conventional risk stratification for therapeutic decision making in these highly vulnerable patients.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and disproportionately affects children of Hispanic/Latino ethnicity in the United States, who have the highest incidence of disease compared with other racial/ethnic groups. Incidence of childhood ALL is similarly high in several Latin American countries, notably in Mexico, and of concern is the rising incidence of childhood ALL in some Hispanic/Latino populations that may further widen this disparity. Prior studies have implicated common germline genetic variants in the increased risk of ALL among Hispanic/Latino children. In this review, we describe the known disparities in ALL incidence as well as patient outcomes that disproportionately affect Hispanic/Latino children across the Americas, and we focus on the role of genetic variation as well as Indigenous American ancestry in the etiology of these disparities. Finally, we discuss future avenues of research to further our understanding of the causes of the disparities in ALL incidence and outcomes in children of Latin American origin, which will be required for future precision prevention efforts.

IntroductionEpidemiological studies around the world on acute leukemia (AL) and risk factors in infants are scarce. Infant AL has been proposed to originate in utero, which facilitates its study by establishing a short exposure time in pregnant women to environmental and dietary factors that could contribute to the risk of or protection against leukemia. We hypothesized that maternal diet during pregnancy may be an important factor involved in AL in offspring.MethodsWe conducted a hospital-based case-control study from 2010 to 2019 on maternal diet during pregnancy in nine high-specialty public hospitals of different health institutions that diagnose and offer treatment to children with AL in Mexico City. Cases (n=109) were children ≤24 months of age with de novo diagnosis of AL, and controls (n=252) were children obtained in hospitals from second-level medical care matched for age, sex, and health institution. Maternal diet during pregnancy was obtained by a semiquantitative food frequency questionnaire. Unconditional logistic regression models were used to assess the association between food groups and infant AL. Potential confounders were assessed by constructing directed acyclic graphs (DAGs) with Dagitty software in which adjusted options were identified for the construction of unconditional logistic regression models.ResultsCases were slightly predominantly female (52.3%). The years of education of the mother in cases and controls was 0-9 on average, and those who reported smoking cigarettes and consuming alcohol during pregnancy did so at a low frequency. Regarding the mother’s diet, the main findings were that the consumption of allium vegetables during pregnancy was inversely associated with AL for medium and high consumption (OR=0.26, 95% CI 0.14-0.46; P-trend< 0.001). In contrast, the high consumption of high-fat dairy products had a positive association with AL (OR=2.37, 95% CI 1.30-4.34; P-trend

Agricultural residues adequate managing contributes to reduce CO2 emissions and easy the circular economy. In this paper, cucumber, tomato and pepper greenhouse crop residues were characterized both chemically and energetically to potential of waste as a biofuel. When compared to other herbaceous and woody biomass, the data show higher moisture, ash and chlorine contents. The gross calorific values of these residues are in the same range as the herbaceous biomass (14.92 MJ/kg), with net values of 13.71, 14.58 and 15.73 MJ/kg for cucumber, tomato and pepper, respectively. The study also included other not common elements, finding the highest values for calcium (13–25 mg/kg) and potassium (23–30 mg/kg). To date, empirical correlations have been defined to predict the CV as a function of total C content (expressed as % in dry weight) for these residues individually. The empirical correlations obtained had maximum absolute errors (MAE) of 0.11, 0.32 and 0.58 % for cucumber, tomato and pepper whereas the marginal mean bias errors (MBE) were 0.016, 0.002 and 0.004 %, respectively, which confirms the value of using this method to determinate the gross calorific value of these residues. The correlations shown provide a useful tool for developing energy production processes based on crop residues, that would appear to be an interesting source of renewable energy to produce heat.

BackgroundChildhood cancer is the leading cause of disease-related mortality among children aged 5–14 years in Mexico, with acute leukemia being the most common cancer among infants. Examining the overall dietary patterns allows for a comprehensive assessment of food and nutrient consumption, providing a more predictive measure of disease risk than individual foods or nutrients. This study aims to evaluate the association between maternal dietary patterns during pregnancy and the risk of acute leukemia in Mexican infants.MethodsA hospital-based case–control study was conducted, comparing 109 confirmed acute leukemia cases with 152 age-matched controls. All participants (≤24 months) were identified at hospitals in Mexico City between 2010 and 2019. Data on a posteriori dietary patterns and other relevant variables were collected through structured interviews and dietary questionnaires. Multivariate logistic regression was employed to estimate the association between maternal dietary patterns during pregnancy and the risk of acute leukemia in infants.ResultsThe “Balanced & Vegetable-Rich” pattern, characterized by a balanced consumption of various food groups and higher vegetable intake, exhibited a negative association with acute leukemia when compared to the “High Dairy & Cereals” Pattern (adjusted odds ratio [OR] = 0.51; 95% confidence interval [CI]: 0.29, 0.90). We observed that mothers who gave birth to girls and adhered to a healthy dietary pattern during pregnancy exhibited significantly lower odds of their children developing AL compared to those who gave birth to boys [OR = 0.32 (95% CI 0.11, 0.97)]. Our results underscore the significance of maternal nutrition as a modifiable factor in disease prevention and the importance of prenatal health education.

IntroductionMaternal dietary consumption during pregnancy has been inconclusively associated with acute leukemia (AL) in infants, probably because epidemiological evidence has emerged mainly from the analysis of one-by-one nutrient, which is not a real-life scenario. Our objective was to evaluate the association between AL in Mexican children under 2 years of age and their mothers’ nutrients concomitant intake during pregnancy, as well as to explore whether there are differences between girls and boys.MethodsWe conducted a study of 110 cases of AL and 252 hospital-based controls in the Mexico City Metropolitan area from 2010 to 2019. We obtained information on maternal intake of 32 nutrients by a food frequency questionnaire and used weighted quantile sum regression to identify nutrient concomitant intakes.ResultsWe found a concomitant intake of nutrients negatively associated with AL (OR 0.17; CI95% 0.03,0.88) only among girls; and we did not find a nutrient concomitant intake positively associated with AL.DiscussionThis is the first study that suggests nutrients that have been individually associated with AL are not necessarily the same in the presence of other nutrients (concomitant intake); as well as that maternal diet might reduce AL risk only in girls.

Introduction: The adipose tissue secretes chemerin and omentin related to metabolic diseases. It has been reported that both proteins encoded by retinoic acid receptor responder protein 2 (RARRES2) and intelectin-1 (ITLN1) genes, respectively, are abnormally expressed in gestational diabetes mellitus (GDM). Aim: To evaluate the expression of these genes in visceral adipose tissue in pregnant women with GDM. Methods: Descriptive cross-sectional study, with two groups, (A) GDM and (B) control group (pregnant women without GDM). Body mass index (BMI), blood pressure, lipids, and glucose were measured. RARRES2 and ITLN1 mRNA expression were evaluated using quantitative real-time Reverse transcription-polymerase chain reaction using TaqMan probes. Statistical analysis was performed using Kolmogórov–Smirnov, Pearson-Spearman correlation, Kruskal–Wallis tests, and R language with Shapiro–Wilk, SPSS V21.0. Results: Sixty-six women were included. Women with normal weight were more frequent in the control group (33.3%) than GDM (15.2%); overweight was similar in both groups (45.5%), and obesity was less common in the control group (21.2%) than GDM (39.3%). No differential expression of RARRES2 and ITLN1 genes among cases and controls were found, but RARRES2 expression differed (P = 0.016) between normal-weight and overweight women in the control group, and ITLN1 expression significantly differed (P = 0.002) between overweight and obese women in the GDM group. Conclusions: ITLN1 could have a role in the GDM severity based on the BMI of the patients.

Los coronavirus (CoV) causan enfermedades respiratorias y entéricas leves, graves o críticas, pudiendo ocasionar la muerte del paciente. Debido a la alta conectividad entre naciones y a la transmisión, actualmente la COVID-19 representa un verdadero problema de salud pública en todo el mundo. El CoV-2 causante del síndrome respiratorio agudo grave (SARS-CoV-2) apareció a finales de diciembre de 2019 en Wuhan, China, y en marzo de 2020 la COVID-19 fue declarada pandemia. En esta revisión se describen las características del genoma y de la proteína espiga del SARS-CoV-2, su papel en la inmunopatogénesis de la COVID-19, la tormenta de citocinas, la actividad citotóxica inducida por células T y la producción de anticuerpos contra el SARS-CoV-2 mediada por células B, así como la eficacia de algunas vacunas, tomando en cuenta las mutaciones presentes en la proteína espiga.

Abstract Background The objective of the FeminFER project was to assess the value of ferric carboxymaltose following a multicriteria decision analysis in obstetrics and gynaecology in Spain. Methods Ferric carboxymaltose (FCM) and ferrous sulphate were evaluated using the EVIDEM framework. Ten stakeholders participated to collect different perspectives. The framework was adapted considering evidence retrieved with a PICO-S search strategy and grey literature. Criteria/subcriteria were weighted by level of relevance and an evidence-based decision-making exercise was developed in each criterion; weights and scores were combined to obtain the value of intervention relative to each criterion/subcriterion, that were further combined into the Modulated Relative Benefit-Risk Balance (MRBRB). Results The most important criterion favouring FCM was Compared Efficacy/Effectiveness (0.183 ± 0.07), followed by Patient Preferences (0.059 ± 0.10). Only Direct medical costs criterion favoured FS (-0.003 ± 0.03). MRBRB favoured FCM; 0.45 ± 0.19; in a scale from -1 to + 1. Conclusions In conclusion, considering the several criteria involved in the decision-making process, participants agreed with the use of FCM according to its MRBRB.

BackgroundThe distribution of RUNX1-RUNXT1, PML-RARA, CBFB-MYH11, BCR-ABL1p210, and KMT2A-MLLT3 in the pediatric population with acute myeloid leukemia (AML) in many countries of Latin America is largely unknown. Therefore, we aimed to investigate the frequency of these fusion genes in children with de novo AML from Mexico City, which has one of the highest incidence rates of acute leukemia in the world. Additionally, we explored their impact in mortality during the first year of treatment.MethodsWe retrospectively analyzed the presence of RUNX1-RUNXT1, PML-RARA, CBFB-MYH11, BCR-ABL1p210, and KMT2A-MLLT3 by RT-PCR among 77 patients (

IntroductionOver the years, the Hispanic population living in the United States has consistently shown high incidence rates of childhood acute leukemias (AL). Similarly, high AL incidence was previously observed in Mexico City (MC). Here, we estimated the AL incidence rates among children under 15 years of age in MC during the period 2010–2017.MethodsThe Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia conducted a study gathering clinical and epidemiological information regarding children newly diagnosed with AL at public health institutions of MC. Crude age incidence rates (cAIR) were obtained. Age-standardized incidence rates worldwide (ASIRw) and by municipalities (ASIRm) were calculated by the direct and indirect methods, respectively. These were reported per million population

BackgroundIn Mexico, the incidence of acute myeloid leukemia (AML) has increased in the last few years. Mortality is higher than in developed countries, even though the same chemotherapy protocols are used. CCAAT Enhancer Binding Protein Alpha (CEBPA) mutations are recurrent in AML, influence prognosis, and help to define treatment strategies. CEBPA mutational profiles and their clinical implications have not been evaluated in Mexican pediatric AML patients.Aim of the StudyTo identify the mutational landscape of the CEBPA gene in pediatric patients with de novo AML and assess its influence on clinical features and overall survival (OS).Materials and MethodsDNA was extracted from bone marrow aspirates at diagnosis. Targeted massive parallel sequencing of CEBPA was performed in 80 patients.ResultsCEBPA was mutated in 12.5% (10/80) of patients. Frameshifts at the N-terminal region were the most common mutations 57.14% (8/14). CEBPA biallelic (CEBPABI) mutations were identified in five patients. M2 subtype was the most common in CEBPA positive patients (CEBPAPOS) (p = 0.009); 50% of the CEBPAPOS patients had a WBC count > 100,000 at diagnosis (p = 0.004). OS > 1 year was significantly better in CEBPA negative (CEBPANEG) patients (p = 0.0001). CEBPAPOS patients (either bi- or monoallelic) had a significantly lower OS (p = 0.002). Concurrent mutations in FLT3, CSF3R, and WT1 genes were found in CEBPAPOS individuals. Their contribution to poor OS cannot be ruled out.ConclusionCEBPA mutational profiles in Mexican pediatric AML patients and their clinical implications were evaluated for the first time. The frequency of CEBPAPOS was in the range reported for pediatric AML (4.5–15%). CEBPA mutations showed a negative impact on OS as opposed to the results of other studies.

BackgroundB-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most frequent pediatric cancer worldwide. Despite improvements in treatment regimens, approximately 20% of the cases cannot be cured, highlighting the necessity for identifying new biomarkers to improve the current clinical and molecular risk stratification schemes. We aimed to investigate whether LINC00173 is a biomarker in ALL and to explore its expression level in other human cancer types.MethodsA nested case–control study including Mexican children with BCP-ALL was conducted. LINC00173 expression was evaluated by qRT-PCR using hydrolysis probes. To validate our findings, RNA-seq expression data from BCP-ALL and normal tissues were retrieved from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) repositories, respectively. LINC00173 expression was also evaluated in solid tumors by downloading available data from The Cancer Genome Atlas (TCGA).ResultsA lower expression of LINC00173 in BCP-ALL cases compared to normal subjects was observed (p < 0.05). ALL patients who carry the TCF3/PBX1 fusion gene displayed lower expression of LINC00173 in contrast to other BCP-ALL molecular subtypes (p < 0.04). LINC00173 underexpression was associated with a high risk to relapse (HR = 1.946, 95% CI = 1.213–3.120) and die (HR = 2.073, 95% CI = 1.211–3.547). Patients with TCF3/PBX1 and underexpression of LINC00173 had the worst prognosis (DFS: HR = 12.24, 95% CI = 5.04–29.71; OS: HR = 11.19, 95% CI = 26–32). TCGA data analysis revealed that underexpression of LINC00173 is also associated with poor clinical outcomes in six new reported tumor types.ConclusionOur findings suggest that LINC00173 is a biomarker of poor prognosis in BCP-ALL and other types of cancer. We observed an association between the expression of LINC00173 and TCF3/PBX1 and the risk to relapse and die in BCP-ALL, which is worse in TCF3/PBX1-positive cases displaying underexpression of LINC00173. Experimental studies are needed to provide insight into the LINC00173 and TCF3/PBX relationship.

Acute hepatopancreatic necrosis (AHPND) is an emerging severe disease caused by strains of Vibrio parahaemolyticus (VpAHPND) in whiteleg shrimp (Litopenaeus vannamei). Mitigating its negative impact, and at the same time minimizing antibiotics treatments, is the major challenge in shrimp aquaculture. A sustainable strategy could be to include immunostimulants in diet. Phytobiotics, harmless plant extracts with immunostimulatory and biocidal activities, are promising candidates. In this study, we evaluated the effectiveness of two diets (E and F) supplemented with phytobiotics (functional diets) in terms of protecting shrimp against AHPND. For this purpose, groups of animals were fed functional or control diets for 4 and 5 weeks and, subsequently, they were challenged with VpAHPND by immersion. We compared the mortality in infected groups and estimated the percentage of carriers by using a specific qPCR in hepatopancreas tissue. The results showed that mortality was significantly lower in the group fed functional diet E and, after a 5-week feeding schedule. This group also showed the lowest percentage of carriers. The pathological effects were also reduced with diet F. Thus, feeding shrimp with phytobiotic-enriched diets in critical periods will be highly beneficial because it increases the host’s resistance to AHPND pathology.

Este artículo aborda las dinámicas de consumo cultural de los estudiantes universitarios desde la relación entre la oferta y la demanda de contenido cultural, y desde la construcción de una agencia cultural de estos actores en el primer año de estudios en la Universidad Veracruzana. Mediante un estudio de caso, con una población de 436 estudiantes y el empleo de un método cuantitativo de tipo bivariado se realiza una aproximación a estos actores sociales y su modo de consumir una oferta virtual y presencial. Entre los hallazgos se encuentra un perfil de estudiantes disruptivos, quienes rompen con estructuras de consumo cultural. Se trata de un fenómeno ajeno al contexto escolar, en donde las prácticas continúan siendo tradicionales.

ETV6::RUNX1 is a genetic rearrangement of good prognosis in children with acute lymphoblastic leukemia (ALL). In Mexico, its prevalence is low in comparison with Caucasian populations. We developed a novel TaqMan one-step RT-qPCR approach to assess the prevalence of four genetic rearrangements in a cohort of Hispanic children with ALL from Mexico City. The prevalence of common fusion gene transcripts was as follows: TCF3::PBX1 7.7%; BCR::ABL1p190 3.3%; and KMT2A::AFF1 2.8%, and ETV6::RUNX1was observed with low prevalence (10.5%) in comparison to that reported for developed countries. This is consistent with previous findings on Mexican children with ALL and similar to those reported on children from Hispanic populations. The confirmation of a low prevalence of ETV6::RUNX1 in children of a Hispanic origin represents an advancement in the description of genetic factors of ALL in these populations.

Abstract Purpose To determine the impact of non-cardiovascular comorbidities on the health-related quality of life (HRQoL) of patients with chronic heart failure (CHF). Methods A scoping review of the scientific literature published between 2009 and 2019 was carried out. Observational studies which assessed the HRQoL of patients with CHF using validated questionnaires and its association with non-cardiovascular comorbidities were included. Results The search identified 1904 studies, of which 21 fulfilled the inclusion criteria to be included for analysis. HRQoL was measured through specific, generic, or both types of questionnaires in 72.2%, 16.7%, and 11.1% of the studies, respectively. The most common comorbidities studied were diabetes mellitus (12 studies), mental and behavioral disorders (8 studies), anemia and/or iron deficiency (7 studies), and respiratory diseases (6 studies). Across studies, 93 possible associations between non-cardiovascular comorbidities and HRQoL were tested, of which 21.5% regarded anemia or iron deficiency, 20.4% mental and behavioral disorders, 20.4% diabetes mellitus, and 14.0% respiratory diseases. Despite the large heterogeneity across studies, all 21 showed that the presence of a non-cardiovascular comorbidity had a negative impact on the HRQoL of patients with CHF. A statistically significant impact on worse HRQoL was found in 84.2% of associations between mental and behavioral disorders and HRQoL (patients with depression had up to 200% worse HRQoL than patients without depression); 73.7% of associations between diabetes mellitus and HRQoL (patients with diabetes mellitus had up to 21.8% worse HRQoL than patients without diabetes mellitus); 75% of associations between anemia and/or iron deficiency and HRQoL (patients with anemia and/or iron deficiency had up to 25.6% worse HRQoL than between patients without anemia and/or iron deficiency); and 61.5% of associations between respiratory diseases and HRQoL (patients with a respiratory disease had up to 21.3% worse HRQoL than patients without a respiratory disease). Conclusion The comprehensive management of patients with CHF should include the management of comorbidities which have been associated with a worse HRQoL, with special emphasis on anemia and iron deficiency, mental and behavioral disorders, diabetes mellitus, and respiratory diseases. An adequate control of these comorbidities may have a positive impact on the HRQoL of patients.

Este artículo se basa en una investigación sobre el análisis de las formas de discriminación por género, etnia-raza, orientación del deseo sexual y discapacidad, en el ámbito universitario. Se efectuó durante los años 2017-2019, con el objetivo de conocer las percepciones del estudiantado de la Universidad Nacional de Costa Rica. Se utilizó un enfoque mixto de investigación por medio de la realización de grupos focales y la aplicación de un cuestionario a una muestra probabilística de estudiantes, con lo cual se evidenció un alto grado de manifestaciones de discriminación.

Summary: Background: Early diagnosis is crucial for patients with pancreatic ductal adenocarcinoma (PDAC). The AXL receptor tyrosine kinase is proteolytically processed releasing a soluble form (sAXL) into the blood stream. Here we explore the use of sAXL as a biomarker for PDAC. Methods: AXL was analysed by immunohistochemistry in human pancreatic tissue samples. RNA expression analysis was performed using TCGA/GTEx databases. The plasma concentrations of sAXL, its ligand GAS6, and CA19-9 were studied in two independent cohorts, the HMar cohort (n = 59) and the HClinic cohort (n = 142), including healthy controls, chronic pancreatitis (CP) or PDAC patients, and in a familial PDAC cohort (n = 68). AXL expression and sAXL release were studied in PDAC cell lines and murine models. Findings: AXL is increased in PDAC and precursor lesions as compared to CP or controls. sAXL determined in plasma from two independent cohorts was significantly increased in the PDAC group as compared to healthy controls or CP patients. Patients with high levels of AXL have a lower overall survival. ROC analysis of the plasma levels of sAXL, GAS6, or CA19-9 in our cohorts revealed that sAXL outperformed CA19-9 for discriminating between CP and PDAC. Using both sAXL and CA19-9 increased the diagnostic value. These results were validated in murine models, showing increased sAXL specifically in animals developing PDAC but not those with precursor lesions or acinar tumours. Interpretation: sAXL appears as a biomarker for early detection of PDAC and PDAC–CP discrimination that could accelerate treatment and improve its dismal prognosis. Funding: This work was supported by grants PI20/00625 (PN), RTI2018-095672-B-I00 (AM and PGF), PI20/01696 (MG) and PI18/01034 (AC) from MICINN-FEDER and grant 2017/SGR/225 (PN) from Generalitat de Catalunya.

BackgroundAcute lymphoblastic leukemia (ALL) is characterized by an abnormal proliferation of immature lymphocytes, in whose development involves both environmental and genetic factors. It is well known that single nucleotide polymorphisms (SNPs) in coding and noncoding genes contribute to the susceptibility to ALL. This study aims to determine whether SNPs in miR-146a, miR-196a-2, miR-499a, and miR-612 genes are associated with the risk to ALL in pediatric Mexican population.MethodsA multicenter case-control study was carried out including patients with de novo diagnosis of ALL and healthy subjects as control group. The DNA samples were obtained from saliva and peripheral blood, and the genotyping of rs2910164, rs12803915, rs11614913, and rs3746444 was performed using the 5′exonuclease technique. Gene-gene interaction was evaluated by the multifactor dimensionality reduction (MDR) software.ResultsmiR-499a rs3746444 showed significant differences among cases and controls. The rs3746444G allele was found as a risk factor to ALL (OR, 1.6 [95% CI, 1.05–2.5]; p = 0.028). The homozygous GG genotype of rs3746444 confers higher risk to ALL than the AA genotype (OR, 5.3 [95% CI, 1.23–23.4]; p = 0.01). Moreover, GG genotype highly increases the risk to ALL in male group (OR, 17.6 [95% CI, 1.04–298.9]; p = 0.00393). In addition, an association in a gender-dependent manner among SNPs located in miR-146a and miR-196a-2 genes and ALL susceptibility was found.ConclusionOur findings suggest that SNP located in miR-499a, miR-146a, and miR-196a-2 genes confer risk to ALL in Mexican children. Experimental analysis to decipher the role of these SNPs in human hematopoiesis could improve our understanding of the molecular mechanism underlying the development of ALL.

Acute lymphoblastic leukemia (ALL) is a malignancy with high heterogeneity in its biological features and treatments. Although the overall survival (OS) of patients with ALL has recently improved considerably, owing to the application of conventional chemo-therapeutic agents, approximately 20% of the pediatric cases and 40–50% of the adult patients relapse during and after the treatment period. The potential mechanisms that cause relapse involve clonal evolution, innate and acquired chemoresistance, and the ability of ALL cells to escape the immune-suppressive tumor response. Currently, immunotherapy in combination with conventional treatment is used to enhance the immune response against tumor cells, thereby significantly improving the OS in patients with ALL. Therefore, understanding the mechanisms of immune evasion by leukemia cells could be useful for developing novel therapeutic strategies.

Objetivo: Analizar las diferencias según el sexo en el perfil clínico de riesgo de los pacientes amputados de miembro inferior por causa no traumática. Método: Estudio retrospectivo descriptivo con 697 pacientes amputados de miembro inferior por causa no traumática, en un Servicio de Angiología y Cirugía Vascular, durante un periodo de 5 años y divididos en función del sexo. Se analizaron variables demográficas (edad) y clínicas (causa, comorbilidad, factores de riesgo cardiovascular y nivel de amputación). Resultados: La edad media (± desviación estándar) de las mujeres fue mayor (75.3 ± 12 frente a 68.9 ± 11 años; p < 0.001) y ellas presentaron mayor frecuencia de factores de riesgo cardiovascular concomitantes, tales como diabetes, hipertensión y obesidad, que los varones, mientras que ellos presentaron mayor frecuencia de tabaquismo. No hubo diferencia significativa entre sexos respecto a la distribución de las causas de amputación, siendo la principal causa la isquémica, destacando la arteriosclerosis. Las mujeres presentaron mayor frecuencia y predisposición para un nivel de amputación mayor. Conclusiones: En nuestro estudio, las mujeres presentaron un perfil de riesgo cardiovascular más desfavorable y el sexo femenino fue un predictor independiente de amputación mayor de miembro inferior por causa no traumática.

Non-specific low back pain (NSLBP) affects many people and represents a high cost for health care. Manual pressure release of myofascial trigger points is used to treat NSLBP and is very effective but difficult to standardize since it is provided by different therapists, which also suffer musculoskeletal complications from this highly repetitive activity. A robot designed for this purpose may help in reducing these problems. Here, we present data from a two-arm, single-blinded, randomized controlled clinical trial evaluating the efficiency of a therapeutic massage robot (ADAMO) in reducing NSLBP (clinicaltrials.gov, registration number: NCT04882748). Forty-four patients were randomly distributed into the two arms of the study (robot vs. control). A physician filled the Oswestry disability index (ODI) before starting the treatment and at the end of it, in a blind fashion. In addition, patients filled a visual analogue scale (VAS) after each of the 10 treatment sessions. The ODI and the VAS were analyzed as the primary and secondary outcome measures. Both treatments (robot and control) resulted in a significantly lower ODI (p < 0.05). On the other hand, robot-treated patients significantly reduced their VAS levels (p = 0.0001) whereas control treatment did not reach statistical significance. Patients of both sexes obtained similar benefits from either treatment. Overweight patients (body mass index ≥ 25kg/m2) in the robot arm benefited more from the treatment (p = 0.008) than patients with normal weight. In conclusion, the ADAMO robot is, at least, as efficient as regular treatment in reducing low back pain, and may be more beneficial for specific patients, such as those with excessive weight.

The extraction method used to obtain biologically active compounds from microalgal biomass may affect the biostimulant capacity of the microalgae. The objective of this assay was to determine the most efficient extraction method to release the active components of the biomass of Chlorella vulgaris (C. vulgaris). Plantlets of Pelargonium × hortorum were grown in a greenhouse and five treatments were applied: C-application with water; M-application with untreated C. vulgaris microalgae; M-US-application with C. vulgaris microalgae treated with ultrasound; M-USHY-application with C. vulgaris microalgae treated with ultrasound and enzymatic hydrolysis; and M-USHYAU-application with C. vulgaris microalgae treated with ultrasound, enzymatic hydrolysis, and autoclaving. All microalgae treatments increased shoot number and stem and plant diameter. The US-treated biomass increased the inflorescence of the plant significantly compared to the control. To extract bioactive compounds from eukaryotic microalgae for plant biostimulating purposes, the US-treatment (or any other method damaging the plasma membrane) of microalgae cell is, or seems to be, suitable.. Macronutrient content in leaves was not affected by the microalgae treatment, except for K.

We present the case of a patient with myocardial infarction and COVID-19 disease who developed hemorrhagic pericardial effusion and cardiac tamponade. The differential diagnosis included post-infarction pericarditis and mechanical complications, thrombolysis, Dressler syndrome, and viral pericarditis. The histopathologic examination of the pericardial tissue sample and electron microscopic examination established the diagnosis. (Level of Difficulty: Advanced.)

Abstract Background Colistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence of carbapenem-resistant gram-negative bacilli (CR-GNB). However, the efficacy and safety of colistin are not well defined. Methods A multicenter prospective randomized trial conducted in 32 European centers compared the efficacy and safety of colistin (4.5 million unit loading dose followed by a maintenance dose of 3 million units every 8 h) versus meropenem (2 g every 8 h), both in combination with levofloxacin (500 mg every 12 h) for 7–14 days in patients with late VAP. Between May 2012 and October 2015, 232 patients were randomly assigned to the 2 treatment groups. The primary endpoint was mortality at 28 days after randomization in the microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical and microbiological cure, renal function at the end of the treatment, and serious adverse events. The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group; therefore, the sample size was not achieved. Results A total of 157 (67.7%) patients were included in the mMITT population, 36 of whom (22.9%) had VAP caused by CR-GNB. In the mMITT population, no significant difference in mortality between the colistin group (19/82, 23.2%) and the meropenem group (19/75, 25.3%) was observed, with a risk difference of − 2.16 (− 15.59 to 11.26, p = 0.377); the noninferiority of colistin was not demonstrated due to early termination and limited number of patients infected by carbapenem-resistant pathogens. Colistin plus levofloxacin increased the incidence of renal failure (40/120, 33.3%, versus 21/112, 18.8%; p = 0.012) and renal replacement therapy (11/120, 9.1%, versus 2/112, 1.8%; p = 0.015). Conclusions This study did not demonstrate the noninferiority of colistin compared with meropenem, both combined with levofloxacin, in terms of efficacy in the empirical treatment of late VAP but demonstrated the greater nephrotoxicity of colistin. These findings do not support the empirical use of colistin for the treatment of late VAP due to early termination. Trial registration ClinicalTrials.gov, NCT01292031. Registered 9 February 2011.

Abstract Background Diabetic nephropathy is a global common cause of chronic kidney disease and end-stage renal disease. A lot of research has been conducted in biomedical sciences, which has enhanced understanding of the pathophysiology of diabetic nephropathy and has expanded the potential available therapies. An increasing number of evidence suggests that genetic alterations play a major role in development and progression of diabetic nephropathy. This systematic review was focused on searching an association between Arg913Gln variation in SLC12A3 gene with diabetic nephropathy in individuals with Type 2 Diabetes and Gitelman Syndrome. Methods An extensive systematic review of the literature was completed using PubMed, EBSCO and Cochrane Library, from their inception to January 2018. The PRISMA guidelines were followed and the search strategy ensured that all possible studies were identified to compile the review. Inclusion criteria for this review were: 1) Studies that analyzed the SLC12A3 gene in individuals with Type 2 Diabetes and Gitelman Syndrome. 2) Use of at least one analysis investigating the association between the Arg913Gln variation of SLC12A3 gene with diabetic nephropathy. 3) Use of a case–control or follow-up design. 4) Investigation of type 2 diabetes mellitus in individuals with Gitelman’s syndrome, with a history of diabetic nephropathy. Results The included studies comprised 2106 individuals with diabetic nephropathy. This review shows a significant genetic association in most studies in the Arg913Gln variation of SLC12A3 gene with the diabetic nephropathy, pointing out that the mutations of this gene could be a key predictor of end-stage renal disease. Conclusions The results showed in this systematic review contribute to better understanding of the association between the Arg913Gln variation of SLC12A3 gene with the pathogenesis of diabetic nephropathy in individuals with T2DM and GS.

Abstract Background Mexico City has one of the highest incidences and mortality rates of acute lymphoblastic leukemia (ALL) in the world and a high frequency of early relapses (17%) and early mortality (15%). Otherwise, childhood overweight and obesity are reaching epidemic proportions. They have been associated with poor outcomes in children with ALL. The aim of present study was to identify if overweight and obesity are predictors of early mortality and relapse in Mexican children with ALL. Methods A multicenter cohort study was conducted. ALL children younger than 15 years old were included and followed-up during the first 24 months after diagnosis. Overweight and obesity were classified according World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Early mortality and early relapses were the main outcomes. Results A total of 1070 children were analyzed. Overweight/obesity at diagnosis were predictors of early mortality (WHO: HR = 1.4, 95%CI:1.0–2.0; CDC: HR = 1.6, 95%CI:1.1–2.3). However, no associations between overweight (WHO: HR = 1.5, 95%CI:0.9–2.5; CDC: HR = 1.0; 95% CI:0.6–1.6) and obesity (WHO: HR = 1.5, 95%CI:0.7–3.2; CDC: HR = 1.4; 95%CI:0.9–2.3) with early relapse were observed. Conclusions Overweight and obese patients embody a subgroup with high risk of dying during leukemia treatment.

Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compared with ER, PR, and HER2‐positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non‐coding RNA (lncRNA) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lncRNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of LncKLHDC7B (ENSG00000226738). A total of 710 lncRNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lncRNA were independently validated. We discovered that LncKLHDC7B (ENSG00000226738) acts as a transcriptional modulator of its neighboring coding gene KLHDC7B in the immunomodulatory subtype. Furthermore, LncKLHDC7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of LncKLHDC7B to induction of apoptosis and inhibition of cell migration and invasion, suggesting that TNBC tumors with enrichment of LncKLHDC7B may exhibit distinct regulatory activity, or that this may be a generalized process in breast cancer. Additionally, in silico analysis confirmed for the first time that the low expression of KLHDC7B and LncKLHDC7B is associated with poor prognosis in patients with breast cancer.

The burden of asthma varies between ancestries, but GWAS have so far focused on mainly European ancestry populations. Here, Daya et al. perform GWAS for asthma in 14,654 individuals of African ancestry and, besides confirming previously known loci, identify two potentially African ancestry-specific loci.

Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tumor in women worldwide. BRCA is a molecularly heterogeneous disease, particularly at gene expression (mRNAs) level. Recent evidence shows that coding RNAs represent only 34% of the total transcriptome in a human cell. The rest of the 66% of RNAs are non−coding, so we might be missing relevant biological, clinical or regulatory information. In this report, we identified two novel tumor types from TCGA with LINC00460 deregulation. We used survival analysis to demonstrate that LINC00460 expression is a marker for poor overall (OS), relapse-free (RFS) and distant metastasis-free survival (DMFS) in basal-like BRCA patients. LINC00460 expression is a potential marker for aggressive phenotypes in distinct tumors, including HPV-negative HNSC, stage IV KIRC, locally advanced lung cancer and basal-like BRCA. We show that the LINC00460 prognostic expression effect is tissue-specific, since its upregulation can predict poor OS in some tumors, but also predicts an improved clinical course in BRCA patients. We found that the LINC00460 expression is significantly enriched in the Basal-like 2 (BL2) TNBC subtype and potentially regulates the WNT differentiation pathway. LINC00460 can also modulate a plethora of immunogenic related genes in BRCA, such as SFRP5, FOSL1, IFNK, CSF2, DUSP7 and IL1A and interacts with miR-103-a-1, in-silico, which, in turn, can no longer target WNT7A. Finally, LINC00460:WNT7A ratio constitutes a composite marker for decreased OS and DMFS in Basal-like BRCA, and can predict anthracycline therapy response in ER-BRCA patients. This evidence confirms that LINC00460 is a master regulator in BRCA molecular circuits and influences clinical outcome.

Almost two decades ago, the sequencing of the human genome and high throughput technologies came to revolutionize the clinical and therapeutic approaches of patients with complex human diseases. In acute lymphoblastic leukemia (ALL), the most frequent childhood malignancy, these technologies have enabled to characterize the genomic landscape of the disease and have significantly improved the survival rates of ALL patients. Despite this, adverse reactions from treatment such as toxicity, drug resistance and secondary tumors formation are still serious consequences of chemotherapy, and the main obstacles to reduce ALL-related mortality. It is well known that germline variants and somatic mutations in genes involved in drug metabolism impact the efficacy of drugs used in oncohematological diseases therapy. So far, a broader spectrum of clinically actionable alterations that seems to be crucial for the progression and treatment response have been identified. Although these results are promising, it is necessary to put this knowledge into the clinics to help physician make medical decisions and generate an impact in patients’ health. This review summarizes the gene variants and clinically actionable mutations that modify the efficacy of antileukemic drugs. Therefore, knowing their genetic status before treatment is critical to reduce severe adverse effects, toxicities and life-threatening consequences in ALL patients.

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period.

Studies have suggested a potential role of somatic mitochondrial mutations in cancer development. To analyze the landscape of somatic mitochondrial mutation in breast cancer and to determine whether mitochondrial DNA (mtDNA) mutational burden is correlated with overall survival (OS), we sequenced whole mtDNA from 92 matched-paired primary breast tumors and peripheral blood. A total of 324 germline variants and 173 somatic mutations were found in the tumors. The most common germline allele was 663G (12S), showing lower heteroplasmy levels in peripheral blood lymphocytes than in their matched tumors, even reaching homoplasmic status in several cases. The heteroplasmy load was higher in tumors than in their paired normal tissues. Somatic mtDNA mutations were found in 73.9% of breast tumors; 59% of these mutations were located in the coding region (66.7% non-synonymous and 33.3% synonymous). Although the CO1 gene presented the highest number of mutations, tRNA genes (T,C, and W), rRNA 12S, and CO1 and ATP6 exhibited the highest mutation rates. No specific mtDNA mutational profile was associated with molecular subtypes of breast cancer, and we found no correlation between mtDNA mutational burden and OS. Future investigations will provide insight into the molecular mechanisms through which mtDNA mutations and heteroplasmy shifting contribute to breast cancer development.

Background: Acute lymphoblastic leukemia (ALL) is the main type of cancer in children. In Mexico and other Hispanic populations, the incidence of this neoplasm is one of the highest reported worldwide. Functional polymorphisms of various enzymes involved in the metabolism of xenobiotics have been associated with an increased risk of developing ALL, and the risk is different by ethnicity. The aims of the present study were to identify whether NQO1, CYP2E1, and NAT2 polymorphisms or some genotype-environmental interactions were associated with ALL risk in Mexican children.Methods: We conducted a case-control study including 478 pediatric patients diagnosed with ALL and 284 controls (children without leukemia). Ancestry composition of a subset of cases and controls was assessed using 32 ancestry informative markers. Genetic-environmental interactions for the exposure to hydrocarbons were assessed by logistic regression analysis.Results: The polymorphisms rs1801280 (OR 1.54, 95% CI 1.21–1.93), rs1799929 (OR 1.96, 95% CI 1.55–2.49), and rs1208 (OR 1.44, 95% CI 1.14–1.81) were found to increase the risk of ALL; being the risks higher under a recessive model (OR 2.20, 95% CI 1.30–1.71, OR 3.87, 95% CI 2.20–6.80, and OR 2.26, 95% CI 1.32–3.87, respectively). Gene-environment interaction analysis showed that NAT2 rs1799929 TT genotype confers high risk to ALL under exposure to fertilizers, insecticides, hydrocarbon derivatives, and parental tobacco smoking. No associations among NQO1, CYP2E1, and ALL were observed.Conclusion: Our study provides evidence for the association between NAT2 polymorphisms/gene-environment interactions, and the risk of childhood ALL in Mexican children.

Introduction Haematopoietic stem cell transplantation (HSCT) is a life-saving treatment for a number of haematological diseases. Graft versus host disease (GVHD) is its main complication and hampers survival. There is strong evidence that intestinal microbiota diversity of the recipient may increase the risk of GVHD worsening survival. Antibiotic regimens used during the early phase of the transplant may influence clinical outcomes by reducing intestinal microbiota diversity. Present guidelines of European Conference on Infections in Leukaemia exhort to optimising antibiotic use in haematological patients including HSCT recipients. The present study aims to investigate if, in HSCT recipients, the optimisation of antibacterial use may preserve intestinal microbiota composition reducing the incidence and severity of acute GVHD and improving relevant clinical outcomes.Methods and analysis This is a prospective longitudinal observational study of two cohorts of HSCT recipients: (1) the intervention cohort includes patients treated in centres in which a predefined strategy of antibiotherapy optimisation is implemented, with the objective of optimising and reducing antibiotic administration according to clinical criteria and (2) the control cohort includes patients treated in centres in which a classic permissive strategy of antibiotic prophylaxis and treatment is used. Adult patient receiving a first HSCT as a treatment for any haematological condition are included. Clinical variables are prospectively recorded and up to five faecal samples are collected for microbiota characterisation at prestablished peritransplant time points. Patients are followed since the preconditioning phase throughout 1-year post-transplant and four follow-up visits are scheduled. Faecal microbiota composition and diversity will be compared between both cohorts along with acute GVHD incidence and severity, severe infections rate, mortality and overall and disease-free survival.Ethics and dissemination The study was approved between 2017 and 2018 by the Ethical Committees of participant centres. Study results will be disseminated through peer-reviewed journals and national and international scientific conferences.Trial registration number NCT03727113

IntroductionBLK has been identified as a risk factor to rheumatoid arthritis (RA) primarily in Asian or European-derived populations. However, this finding has not been evaluated in other populations such as Latin-Americans, except for Colombians. On the other hand, BANK1 single nucleotide variants (SNVs) have been scarcely studied in RA patients.ObjectiveThe aim of this study was to determine whether the BLK rs2736340T/C, rs13277113A/G, and BANK1 rs10516487G/A (R61H) and rs3733197G/A (A383T) polymorphisms are risk factors to RA in a sample of patients from Central Mexico.Materials and MethodsWe studied 957 women; 487 controls and 470 patients with RA by means of a TaqMan® SNP genotyping assay with fluorescent probes for the BLK rs13277113A/G, rs2736340T/C and BANK1 10516487G/A (R61H) and rs3733197G/A (A383T) variants.ResultThe BLK rs2736340T/C and rs13277113A/G variants were associated with risk for RA: C vs T; OR 1.39, p = 0.001, and G vs A; OR 1.37, p = 0.004, respectively. In addition, there was also an association between BANK1 R61H and RA: A vs G; OR 1.49, p = 0.003, but no with BANK1 A383T. We also identified an interaction significant between genotypes of BLK rs2736340T/C-BANK1 rs10516487G/A and RA: OR 1.65, p = 0.0001.ConclusionsOur data suggest that both BLK and BANK1 confer susceptibility to RA in Mexican patients. The individual association of BANK1 rs1054857G/A with RA had not been previously reported in a particular population (except for pooled patients from several countries), therefore, our study presents the first evidence of association between this BANK1 variant and RA.

Abstract In Mexico, due to the high rates of diabetes, overweight, and obesity, there has also been noted an increased newborn weight, which may be contributing to the elevated incidence rate of childhood acute leukemia (AL). We conducted a case–control study in public hospitals of Mexico City aimed to know whether a greater weight at birth is associated with a higher risk of developing leukemia. We included incident cases with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) diagnosed between 2010 and 2015. Controls were frequency‐matched to the cases by age, sex, and health institution. Logistic regression analysis was performed adjusting risks by child's sex, overcrowding index, birth order, and mother's age at the time of pregnancy. Adjusted odds ratios (aORs) and 95% confidence intervals were calculated. A total of 1455 cases and 1455 controls were included. An evident association between ALL and child's birthweight ≥2500 g was found (aOR 2.06; 95% CI: 1.59, 2.66) and also, in those with birthweight ≥3500 g (aOR 1.19; 95% CI: 1.00, 1.41). In AML patients with birthweight ≥2500 g and ≥3500 g, an aOR of 1.77 (95% CI: 1.07, 2.94) and 1.42 (95% CI: 1.03–1.95) was observed, respectively. No association was noticed with either type of AL and a birthweight ≥4000 g. To sum up, we found a moderate association between not having a low birthweight and an increased risk of acute leukemias. Birthweight ≥3500 g was also a risk factor for both types of leukemia. This suggests that a greater birthweight may increase the risk of acute leukemias in Mexican children.