First large-scale study reveals important losses of managed honey bee and stingless bee colonies in Latin America.

Over the last quarter century, increasing honey bee colony losses motivated standardized large-scale surveys of managed honey bees (Apis mellifera), particularly in Europe and the United States. Here we present the first large-scale standardized survey of colony losses of managed honey bees and stingless bees across Latin America. Overall, 1736 beekeepers and 165 meliponiculturists participated in the 2-year survey (2016-2017 and 2017-2018). On average, 30.4% of honey bee colonies and 39.6% of stingless bee colonies were lost per year across the region. Summer losses were higher than winter losses in stingless bees (30.9% and 22.2%, respectively) but not in honey bees (18.8% and 20.6%, respectively). Colony loss increased with operation size during the summer in both honey bees and stingless bees and decreased with operation size during the winter in stingless bees. Furthermore, losses differed significantly between countries and across years for both beekeepers and meliponiculturists. Overall, winter losses of honey bee colonies in Latin America (20.6%) position this region between Europe (12.5%) and the United States (40.4%). These results highlight the magnitude of bee colony losses occurring in the region and suggest difficulties in maintaining overall colony health and economic survival for beekeepers and meliponiculturists.

Decoding the mechanism governing the structural stability of wheat germ agglutinin and its isolated domains: A combined calorimetric, NMR, and MD simulation study.

Wheat germ agglutinin (WGA) demonstrates potential as an oral delivery agent owing to its selective binding to carbohydrates and its capacity to traverse biological membranes. In this study, we employed differential scanning calorimetry and molecular dynamics simulations to comprehensively characterize the thermal unfolding process of both the complete lectin and its four isolated domains. Furthermore, we present the nuclear magnetic resonance structures of three domains that were previously lacking experimental structures in their isolated forms. Our results provide a collective understanding of the energetic and structural factors governing the intricate unfolding mechanism of the complete agglutinin, shedding light on the specific role played by each domain in this process. The analysis revealed negligible interdomain cooperativity, highlighting instead significant coupling between dimer dissociation and the unfolding of the more labile domains. By comparing the dominant interactions, we rationalized the stability differences among the domains. Understanding the structural stability of WGA opens avenues for enhanced drug delivery strategies, underscoring its potential as a promising carrier throughout the gastrointestinal environment.

Validation of the transcranial Doppler rescue criteria for mechanical thrombectomy.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) identifies acute stroke patients with arterial occlusion where treatment may not effectively open the blocked vessel. This study aimed to examine the clinical utility and prognostic value of TCD flow findings in patients enrolled in a multicenter prospective study (CLOTBUST-PRO). METHODS: Patients enrolled with intracranial occlusion on computed tomography angiography (CTA) who underwent urgent TCD evaluation before intravenous thrombolysis was included in this analysis. TCD findings were assessed using the mean flow velocity (MFV) ratio, comparing the reciprocal ratios of the middle cerebral artery (MCA) depths bilaterally (affected MCA-to-contralateral MCA MFV [aMCA/cMCA MFV ratio]). RESULTS: A total of 222 patients with intracranial occlusion on CTA were included in the study (mean age: 64 ± 14 years, 62% men). Eighty-eight patients had M1 MCA occlusions; baseline mean National Institutes of Health Stroke Scale (NIHSS) score was 16, and a 24-hour mean NIHSS score was 10 points. An aMCA/cMCA MFV ratio of <.6 had a sensitivity of 99%, specificity of 16%, positive predictive value (PV) of 60%, and negative PV of 94% for identifying large vessel occlusion (LVO) including M1 MCA, terminal internal carotid artery, or tandem ICA/MCA. Thrombolysis in Brain Ischemia scale, with (grade ≥1) compared to without flow (grade 0), showed a sensitivity of 17.1%, specificity of 86.9%, positive PV of 62%, and negative PV of 46% for identifying LVO. CONCLUSIONS: TCD is a valuable modality for evaluating arterial circulation in acute ischemic stroke patients, demonstrating significant potential as a screening tool for intravenous/intra-arterial lysis protocols.

Protein tyrosine phosphatase 1B (PTP1B) function, structure, and inhibition strategies to develop antidiabetic drugs.

Tyrosine protein phosphatase non-receptor type 1 (PTP1B; also known as protein tyrosine phosphatase 1B) is a member of the protein tyrosine phosphatase (PTP) family and is a soluble enzyme that plays an essential role in different physiological processes, including the regulation of metabolism, specifically in insulin and leptin sensitivity. PTP1B is crucial in the pathogenesis of type 2 diabetes mellitus and obesity. These biological functions have made PTP1B validated as an antidiabetic and anti-obesity, and potentially anticancer, molecular target. Four main approaches aim to inhibit PTP1B: orthosteric, allosteric, bidentate inhibition, and PTPN1 gene silencing. Developing a potent and selective PTP1B inhibitor is still challenging due to the enzyme's ubiquitous expression, subcellular location, and structural properties. This article reviews the main advances in the study of PTP1B since it was first isolated in 1988, as well as recent contextual information related to the PTP family to which this protein belongs. Furthermore, we offer an overview of the role of PTP1B in diabetes and obesity, and the challenges to developing selective, effective, potent, bioavailable, and cell-permeable compounds that can inhibit the enzyme.

Impact of Direct Transport to Thrombectomy-Capable Center vs. Nearby/Distant Local Stroke Centers on Stroke Outcome in Patients Undergoing Thrombectomy: A Real-Life Study.

Our aim was to compare the stroke outcomes of a direct transfer (DT) to a thrombectomy-capable center vs. initial care at two local stroke centers: a nearby hospital (NH, 36 km) and a distant hospital (DH, 113 km). Patients who underwent a mechanical thrombectomy were analyzed (February 2017-October 2021), and the outcome was considered favorable if the modified Rankin scale (mRS) score was ≤ 2 at three months. A total of 300 patients were included, 55 of which were transferred from the NH and 58 from the DH. There was a difference in the median (IQR) transfer time of 39 min between the hospitals (149 min for the NH vs. 188 min for the DH, p = 0.003). After adjusting for confounding variables, a secondary transfer from the DH, compared to a DT, was associated with a lower functional independence: mRS score ≤ 2 (OR = 0.37, 95% CI = 0.14-0.97, p = 0.043), without significant differences in the mortality between the groups. These differences were not observed in patients from the NH. Conclusions: A secondary transfer from a distant hospital was associated with a poorer functional outcome at 3 months. This unfavorable outcome was not observed among patients transferred from a nearby hospital. These findings highlight the importance of categorizing the suitability of one transfer model over another based on the proximity of hospitals to the thrombectomy center, but also in accordance with organizational and geographic characteristics that vary within each health region.

Thyroid abscess, an uncommon diagnosis: A case report and mini­review of the literature.

Thyroid abscess is a rare entity, commonly experienced by immunocompromised patients, or those who have anatomical abnormalities or a pre-existing thyroid disease. An early diagnosis continued by treatment with antibiotics and drainage of the abscess is the recommended therapeutic strategy for such cases. The present study describes a clinical case of this rare event, and also provides a brief literature review. The present study describes the case of a 48-year-old healthy male with no medical antecedents, apart from acute prostatitis treated with antibiotics for 6 days prior, who visited the Emergency Department of the authors' hospital with neck pain and progressive swelling of the mass. Diagnostic imaging confirmed the authors' suspicion of an abscess and revealed the lesion displacing the airway to the contralateral side. This restricted the mobility of the neck of the patient. As an emergency measure, the patient was then taken to the operating room for a neck examination. A hemithyroidectomy was finally performed. Following a prolonged hospital duration, he was discharged from the hospital and his recovery was uneventful without any voice alterations, hypocalcemia or recurrence.

Nanostructures of etherified arabinoxylans and the effect of arabinose content on material properties.

To further our understanding of a thermoplastic arabinoxylan (AX) material obtained through an oxidation-reduction-etherification pathway, the role of the initial arabinose:xylose ratio on the material properties was investigated. Compression molded films with one molar substitution of butyl glycidyl ether (BGE) showed markedly different tensile behaviors. Films made from low arabinose AX were less ductile, while those made from high arabinose AX exhibited elastomer-like behaviors. X-ray scattering confirmed the presence of nanostructure formation resulting in nano-domains rich in either AX or BGE, from side chain grafting. The scattering data showed variations in the presence of ordered structures, nano-domain sizes and their temperature response between AX with different arabinose contents. In dynamic mechanical testing, three transitions were observed at approximately -90 °C, -50 °C and 80 °C, with a correlation between samples with more structured nano-domains and those with higher onset transition temperatures and lower storage modulus decrease. The mechanical properties of the final thermoplastic AX material can therefore be tuned by controlling the composition of the starting material.

Cultivable Microbiome Approach Applied to Cervical Cancer Exploration.

Traditional microbiological methodology is valuable and essential for microbiota composition description and microbe role assignations at different anatomical sites, including cervical and vaginal tissues; that, combined with molecular biology strategies and modern identification approaches, could give a better perspective of the microbiome under different circumstances. This pilot work aimed to describe the differences in microbiota composition in non-cancer women and women with cervical cancer through a culturomics approach combining culture techniques with Vitek mass spectrometry and 16S rDNA sequencing. To determine the possible differences, diverse statistical, diversity, and multivariate analyses were applied; the results indicated a different microbiota composition between non-cancer women and cervical cancer patients. The Firmicutes phylum dominated the non-cancer (NC) group, whereas the cervical cancer (CC) group was characterized by the predominance of Firmicutes and Proteobacteria phyla; there was a depletion of lactic acid bacteria, an increase in the diversity of anaerobes, and opportunistic and non-typical human microbiota isolates were present. In this context, we hypothesize and propose a model in which microbial composition and dynamics may be essential for maintaining the balance in the cervical microenvironment or can be pro-oncogenesis microenvironmental mediators in a process called Ying-Yang or have a protagonist/antagonist microbiota role.

Non-invasive brain stimulation for functional recovery in animal models of stroke: A systematic review.

Motor and cognitive dysfunction occur frequently after stroke, severely affecting a patient´s quality of life. Recently, non-invasive brain stimulation (NIBS) has emerged as a promising treatment option for improving stroke recovery. In this context, animal models are needed to improve the therapeutic use of NIBS after stroke. A systematic review was conducted based on the PRISMA statement. Data from 26 studies comprising rodent models of ischemic stroke treated with different NIBS techniques were included. The SYRCLE tool was used to assess study bias. The results suggest that both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) improved overall neurological, motor, and cognitive functions and reduced infarct size both in the short- and long-term. For tDCS, it was observed that either ipsilesional inhibition or contralesional stimulation consistently led to functional recovery. Additionally, the application of early tDCS appeared to be more effective than late stimulation, and tDCS may be slightly superior to rTMS. The optimal stimulation protocol and the ideal time window for intervention remain unresolved. Future directions are discussed for improving study quality and increasing their translational potential.

Deletion of the protein tyrosine phosphatase PTPN22 for adoptive T cell therapy facilitates CTL effector function but promotes T cell exhaustion.

BACKGROUND: Adoptive cell therapy (ACT) is a promising strategy for treating cancer, yet it faces several challenges such as lack of long-term protection due to T cell exhaustion induced by chronic TCR stimulation in the tumor microenvironment. One benefit of ACT, however, is that it allows for cellular manipulations, such as deletion of the phosphotyrosine phosphatase non-receptor type 22 (PTPN22), which improves CD8+ T cell antitumor efficacy in ACT. We tested whether Ptpn22KO cytolytic T cells (CTLs) were also more effective than Ptpn22WT CTL in controlling tumors in scenarios that favor T cell exhaustion. METHODS: Tumor control by Ptpn22WT and Ptpn22KO CTL was assessed following adoptive transfer of low numbers of CTL to mice with subcutaneously implanted MC38 tumors. Tumor infiltrating lymphocytes were isolated for analysis of effector functions. An in vitro assay was established to compare CTL function in response to acute and chronic restimulation with antigen-pulsed tumor cells. The expression of effector and exhaustion-associated proteins by Ptpn22WT and Ptpn22KO T cells was followed over time in vitro and in vivo using the ID8 tumor model. Finally, the effect of PD-1 and TIM-3 blockade on Ptpn22KO CTL tumor control was assessed using monoclonal antibodies and CRISPR/Cas9-mediated knockout. RESULTS: Despite having improved effector function at the time of transfer, Ptpn22KO CTL became more exhausted than Ptpn22WT CTL, characterized by more rapid loss of effector functions, and earlier and higher expression of inhibitory receptors (IRs), particularly the terminal exhaustion marker TIM-3. TIM-3 expression, under the control of the transcription factor NFIL3, was induced by IL-2 signaling which was enhanced in Ptpn22KO cells. Antitumor responses of Ptpn22KO CTL were improved following PD-1 blockade in vivo, yet knockout or antibody-mediated blockade of TIM-3 did not improve but further impaired tumor control, indicating TIM-3 signaling itself did not drive the diminished function seen in Ptpn22KO CTL. CONCLUSIONS: This study questions whether TIM-3 plays a role as an IR and highlights that genetic manipulation of T cells for ACT needs to balance short-term augmented effector function against the risk of T cell exhaustion in order to achieve longer-term protection.

The synergy of halotolerant PGPB and mauran mitigates salt stress in tomato (Solanum lycopersicum) via osmoprotectants accumulation.

Salinity stress is one of the major abiotic factors limiting sustainable agriculture. Halotolerant plant growth-promoting bacteria (PGPB) increased salt stress tolerance in plants, but the mechanisms underlying the tolerance are poorly understood. This study investigated the PGP activity of four halotolerant bacteria under salinity stress and the tomato salt-tolerance mechanisms induced by the synergy of these bacteria with the exopolysaccharide (EPS) mauran. All PGPB tested in this study were able to offer a significant improvement of tomato plant biomass under salinity stress; Peribacillus castrilensis N3 being the most efficient one. Tomato plants treated with N3 and the EPS mauran showed greater tolerance to NaCl than the treatment in the absence of EPS and PGPB. The synergy of N3 with mauran confers salt stress tolerance in tomato plants by increasing sodium transporter genes' expression and osmoprotectant content, including soluble sugars, polyols, proline, GABA, phenols and the polyamine putrescine. These osmolytes together with the induction of sodium transporter genes increase the osmotic adjustment capacity to resist water loss and maintain ionic homeostasis. These findings suggest that the synergy of the halotolerant bacterium N3 and the EPS mauran could enhance tomato plant growth by mitigating salt stress and could have great potential as an inductor of salinity tolerance in the agriculture sector.

External Validation of SAFE Score to Predict Atrial Fibrillation Diagnosis after Ischemic Stroke: A Retrospective Multicenter Study.

Introduction: The screening for atrial fibrillation (AF) scale (SAFE score) was recently developed to provide a prediction of the diagnosis of AF after an ischemic stroke. It includes 7 items: age ≥ 65 years, bronchopathy, thyroid disease, cortical location of stroke, intracranial large vessel occlusion, NT-ProBNP ≥250 pg/mL, and left atrial enlargement. In the internal validation, a good performance was obtained, with an AUC = 0.88 (95% CI 0.84-0.91) and sensitivity and specificity of 83% and 80%, respectively, for scores ≥ 5. The aim of this study is the external validation of the SAFE score in a multicenter cohort. Methods: A retrospective multicenter study, including consecutive patients with ischemic stroke or transient ischemic attack between 2020 and 2022 with at least 24 hours of cardiac monitoring. Patients with previous AF or AF diagnosed on admission ECG were excluded. Results: Overall, 395 patients were recruited for analysis. The SAFE score obtained an AUC = 0.822 (95% CI 0.778-0.866) with a sensitivity of 87.2%, a specificity of 65.4%, a positive predictive value of 44.1%, and a negative predictive value of 94.3% for a SAFE score ≥ 5, with no significant gender differences. Calibration analysis in the external cohort showed an absence of significant differences between the observed values and those predicted by the model (Hosmer-Lemeshow's test 0.089). Conclusions: The SAFE score showed adequate discriminative ability and calibration, so its external validation is justified. Further validations in other external cohorts or specific subpopulations of stroke patients might be required.

Cobertura algal en dos sitios del Parque Nacional de Guanahacabibes, plataforma suroccidental de Cuba

Introducción: Las comunidades de macroalgas marinas del Parque Nacional Guanahacabibes no han sido estudiadas desde el punto de vista cuantitativo, a pesar de la influencia que la vegetación submarina tiene sobre la estructura y el funcionamiento de los ecosistemas costeros, componente que hasta ahora ha sido subestimado en la región. Objetivo: Evaluar la variación temporal y espacial de los géneros de macroalgas en dos sitios de María La Gorda, sur del Parque Nacional de Guanahacabibes, y evaluar la salud del arrecife de acuerdo con la cobertura de los diferentes morfo-tipos de macroalgas predominantes. Metodología: El muestreo fue cuatrimestral entre febrero 2014 y marzo 2017 en Yemayá y Laberinto, mediante buceo autónomo a una profundidad de 10 m. La cobertura algal fue estimada siguiendo la metodología AGRRA. Se usaron ocho transectos de 20 m por sitio de muestreo de acuerdo con las condiciones del arrecife y la forma del fondo. Cada cinco metros se colocó un cuadrante de 25 x 25 cm. Se calculó el porcentaje de cobertura que aporta cada género y de los grupos morfofuncionales a la cobertura total. Resultados: Los géneros dominantes durante el periodo de estudio fueron: Dictyota, Lobophora y Halimeda. Las algas carnosas y calcáreas mostraron mayor cubrimiento en Laberinto (carnosas= 57.8 ±15.6; calcáreas = 8.3 ± 6.8) que en Yemayá, (carnosas = 47.3 ± 23.1; calcáreas = 8.5 ± 9.3). Las formas costrosas son más abundantes en Yemayá (17.1 ± 15.1) que en Laberinto (7.7 ± 10). El índice de las carnosas fue superior en Laberinto (225.7 ± 110.2). Conclusión: La disminución en los niveles de cobertura de algas costrosas y la dominancia de formas carnosas como Dictyota y Lobophora en la zona de estudio, evidencian el deterioro en ambos sitios, a pesar de las políticas de conservación de parques nacionales.

Introduction: The macroalgal communities of the Guanahacabibes National Park have been poorly studied from the quantitative point of view, despite the influence that underwater vegetation has on the structure and functioning of coastal ecosystems, a component that until now has been underestimated in the Cuba region. Objetive: To evaluate the temporal and spatial variation of the macroalgal genera in two sites of María La Gorda, south of the Guanahacabibes National Park, and evaluate the reef health according to the coverage of the different predominant macroalgal morphotypes. Methodology: Sampling took place quarterly between February 2014 and March 2017, in Laberinto and Yemayá by SCUBA diving at a depth of 10 m. The algal coverage was estimated following the AGRRA methodology. Eight 20 m transects per sampling site were used according to reef conditions and bottom shape. Every five meters a 25 x 25 cm square was placed. The coverage (%) contributed per genus and morpho-functional group to the total coverage found was calculated. Results: The dominant genera during the study period were: Dictyota, Lobophora and Halimeda. Fleshy and calcareous algae showed greater coverage in Laberinto (fleshy= 57.8 ± 15.6; calcareous = 8.3 ± 6.8) than in Yemayá (fleshy = 47.3 ± 23.1; calcareous = 8.5 ± 9.3). Crustose algae were more abundant in Yemayá (17.1 ± 15.1) than in Laberinto (7.7 ± 10). The fleshy index was higher in Laberinto (225.7 ± 110.2). Conclusion: The decrease in the levels of crustose algal cover, as well as the dominance of fleshy forms Dictyota and Lobophora in the study area, shows the deterioration in both sites, despite the conservation policies of national parks.

New Organotin (IV) Compounds Derived from Dehydroacetic Acid and Thiosemicarbazides: Synthesis, Rational Design, Cytotoxic Evaluation, and Molecular Docking Simulation.

Organotin complexes were prepared through a one-pot reaction with three components by reacting thiosemicarbazide or 4-methyl-3-thiosemicarbazide or 4-phenylthiosemicarbazide, dehydroacetic acid (DHA) and dibutyl, diphenyl, dicyclohexyl, and bis[(trimethylsilyl)methyl]tin(IV) oxides; all complexes were characterized by infrared (IR), ultraviolet-visible (UV-vis), mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy. The 119Sn NMR revealed chemical shifts corresponding to a pentacoordinated environment in solution. The X-ray crystallography of the two complexes evidenced the formation of monomeric complexes with a pentacoordinated geometry around tin via three donor atoms from the ligand, the sulfur of the thiol, the nitrogen of the imine group, and the oxygen of the pyran ring. The geometries of the five-coordinated complexes 3a (Bu2SnL3), 3c (Ph2SnL3), and 3d (Cy2SnL3) acid were intermediate between square pyramidal and trigonal bipyramidal, and complex 1a (Bu2SnL1) adopted a bipyramidal trigonal geometry (BPT). The sulforhodamine B assay assessed the cytotoxicity of organotin(IV) complexes against the MDA-MB-231 and MCF-7 (human mammary adenocarcinoma) cell lines and one normal COS-7 (African green monkey kidney fibroblast). The IC50 values evidenced a significant antiproliferative effect on cancer cells; the complexes were more potent than the positive cisplatin control and the corresponding ligands, dehydroacetic acid thiosemicarbazone (L1), dehydroacetic acid-N(4)-methylthiosemicarbazone (L2), and dehydroacetic acid-N(4)-phenylthiosemicarbazone (L3). The IC50 values also indicated that the organotin(IV) complexes were more cytotoxic against the triple-negative breast cell line MDA-MB-231 than MCF-7, inducing significant morphological alterations. The interactions of organotin(IV) 1c (Ph2SnL1), 1d (Cy2SnL1), and 1e (((CH3)3SiCH2)2SnL1) were evaluated with ss-DNA by fluorescence; intensity changes of the fluorescence were indicative of the displacement of ethidium bromide (EB), confirming the interaction of the organotin(IV) complexes with ss-DNA; the results showed a DNA binding affinity. The thermodynamic parameters obtained through isothermal titration calorimetry showed that the interaction of 1c (Ph2SnL1), with ss-ADN, was exothermic. Molecular docking studies also demonstrated that the organotin(IV) complexes were intercalated in DNA by conventional hydrogen bonds, carbon-hydrogen bonds, and π-alkyl interactions. These complexes furthermore showed a greater affinity towards DNA than cisplatin.

External Validation and Recalibration of a Mortality Prediction Model for Patients with Ischaemic Stroke.

BACKGROUND: Stroke is a highly prevalent disease that can provoke severe disability. We evaluate a predictive model based on the Minimum Basic Data Set (MBDS) compiled by the Spain Health Ministry, obtained for the period 2008-2012 for patients with ischaemic stroke in Spain, to establish the model's validity and to optimise its calibration. The MBDS is the main clinical-administrative database for hospitalisations recorded in Spain, and to our knowledge, no predictive models for stroke mortality have previously been developed using this resource. The main study aim is to perform an external validation and recalibration of the coefficients of this predictive model with respect to a chronologically later cohort. MATERIAL AND METHODS: External validation (testing the model on a different cohort to assess its performance) and recalibration (validation with optimisation of model coefficients) were performed using the MBDS for patients admitted for ischaemic stroke in the period 2016-2018. A cohort study was designed, in which a recalibrated model was obtained by applying the variables of the original model without their coefficients. The variables from the original model were then applied to the subsequent cohort, together with the coefficients from the initial model. The areas under the curve (AUC) of the recalibration and the external validation procedure were compared. RESULTS: The recalibrated model produced an AUC of 0.743 and was composed of the following variables: age (odds ratio, OR:1.073), female sex (OR:1.143), ischaemic heart disease (OR:1.192), hypertension (OR:0.719), atrial fibrillation (OR:1.414), hyperlipidaemia (OR:0.652), heart failure (OR:2.133) and posterior circulation stroke (OR: 0.755). External validation produced an AUC of 0.726. CONCLUSIONS: The recalibrated clinical model thus obtained presented moderate-high discriminant ability and was generalisable to predict death for patients with ischaemic stroke. Rigorous external validation slightly decreased the AUC but confirmed the validity of the baseline model for the chronologically later cohort.

SEN1990 is a predicted winged helix-turn-helix protein involved in the pathogenicity of Salmonella enterica serovar Enteritidis and the expression of the gene oafB in the SPI-17.

Excisable genomic islands (EGIs) are horizontally acquired genetic elements that harbor an array of genes with diverse functions. ROD21 is an EGI found integrated in the chromosome of Salmonella enterica serovar Enteritidis (Salmonella ser. Enteritidis). While this island is known to be involved in the capacity of Salmonella ser. Enteritidis to cross the epithelial barrier and colonize sterile organs, the role of most ROD21 genes remains unknown, and thus, the identification of their function is fundamental to understanding the impact of this EGI on bacterium pathogenicity. Therefore, in this study, we used a bioinformatical approach to evaluate the function of ROD21-encoded genes and delve into the characterization of SEN1990, a gene encoding a putative DNA-binding protein. We characterized the predicted structure of SEN1990, finding that this protein contains a three-stranded winged helix-turn-helix (wHTH) DNA-binding domain. Additionally, we identified homologs of SEN1990 among other members of the EARL EGIs. Furthermore, we deleted SEN1990 in Salmonella ser. Enteritidis, finding no differences in the replication or maintenance of the excised ROD21, contrary to what the previous Refseq annotation of the protein suggests. High-throughput RNA sequencing was carried out to evaluate the effect of the absence of SEN1990 on the bacterium's global transcription. We found a downregulated expression of oafB, an SPI-17-encoded acetyltransferase involved in O-antigen modification, which was restored when the deletion mutant was complemented ectopically. Additionally, we found that strains lacking SEN1990 had a reduced capacity to colonize sterile organs in mice. Our findings suggest that SEN1990 encodes a wHTH domain-containing protein that modulates the transcription of oafB from the SPI-17, implying a crosstalk between these pathogenicity islands and a possible new role of ROD21 in the pathogenesis of Salmonella ser. Enteritidis.

Evaluation of factors leading to poor outcomes for pediatric acute lymphoblastic leukemia in Mexico: a multi-institutional report of 2,116 patients.

Background and aims: Pediatric acute lymphoblastic leukemia (ALL) survival rates in low- and middle-income countries are lower due to deficiencies in multilevel factors, including access to timely diagnosis, risk-stratified therapy, and comprehensive supportive care. This retrospective study aimed to analyze outcomes for pediatric ALL at 16 centers in Mexico. Methods: Patients <18 years of age with newly diagnosed B- and T-cell ALL treated between January 2011 and December 2019 were included. Clinical and biological characteristics and their association with outcomes were examined. Results: Overall, 2,116 patients with a median age of 6.3 years were included. B-cell immunophenotype was identified in 1,889 (89.3%) patients. The median white blood cells at diagnosis were 11.2.5 × 103/mm3. CNS-1 status was reported in 1,810 (85.5%), CNS-2 in 67 (3.2%), and CNS-3 in 61 (2.9%). A total of 1,488 patients (70.4%) were classified as high-risk at diagnosis. However, in 52.5% (991/1,889) of patients with B-cell ALL, the reported risk group did not match the calculated risk group allocation based on National Cancer Institute (NCI) criteria. Fluorescence in situ hybridization (FISH) and PCR tests were performed for 407 (19.2%) and 736 (34.8%) patients, respectively. Minimal residual disease (MRD) during induction was performed in 1,158 patients (54.7%). The median follow-up was 3.7 years. During induction, 191 patients died (9.1%), and 45 patients (2.1%) experienced induction failure. A total of 365 deaths (17.3%) occurred, including 174 deaths after remission. Six percent (176) of patients abandoned treatment. The 5-year event-free survival (EFS) was 58.9% ± 1.7% for B-cell ALL and 47.4% ± 5.9% for T-cell ALL, while the 5-year overall survival (OS) was 67.5% ± 1.6% for B-cell ALL and 54.3% ± 0.6% for T-cell ALL. The 5-year cumulative incidence of central nervous system (CNS) relapse was 5.5% ± 0.6%. For the whole cohort, significantly higher outcomes were seen for patients aged 1-10 years, with DNA index >0.9, with hyperdiploid ALL, and without substantial treatment modifications. In multivariable analyses, age and Day 15 MRD continued to have a significant effect on EFS. Conclusion: Outcomes in this multi-institutional cohort describe poor outcomes, influenced by incomplete and inconsistent risk stratification, early toxic death, high on-treatment mortality, and high CNS relapse rate. Adopting comprehensive risk-stratification strategies, evidence-informed de-intensification for favorable-risk patients and optimized supportive care could improve outcomes.

The invasive margin of early-stage human colon tumors is infiltrated with neutrophils of an antitumoral phenotype.

Neutrophils infiltrate several types of cancer; however, whether their presence is associated with disease progression remains controversial. Here, we show that colon tumors overexpress neutrophil chemoattractants compared to healthy tissues, leading to their recruitment to the invasive margin and the central part of colon tumors. Of note, tumor-associated neutrophils expressing tumor necrosis factor α, which usually represents an antitumoral phenotype, were predominantly located in the invasive margin. Tumor-associated neutrophils from the invasive margin displayed an antitumoral phenotype with higher ICAM-1 and CD95 expression than neutrophils from healthy adjacent tissues. A higher neutrophil/lymphocyte ratio was found at later stages compared to the early phases of colon cancer. A neutrophil/lymphocyte ratio ≤3.5 predicted tumor samples had significantly more neutrophils at the invasive margin and the central part. Moreover, tumor-associated neutrophils at the invasive margin of early-stage tumors showed higher ICAM-1 and CD95 expression. Coculture of colon cancer cell lines with primary neutrophils induced ICAM-1 and CD95 expression, confirming our in situ findings. Thus, our data demonstrate that tumor-associated neutrophils with an antitumoral phenotype characterized by high ICAM-1 and CD95 expression infiltrate the invasive margin of early-stage colon tumors, suggesting that these cells can combat the disease at its early courses. The presence of tumor-associated neutrophils with antitumoral phenotype could help predict outcomes of patients with colon cancer.