Echinobase: leveraging an extant model organism database to build a knowledgebase supporting research on the genomics and biology of echinoderms.

Echinobase (www.echinobase.org) is a third generation web resource supporting genomic research on echinoderms. The new version was built by cloning the mature Xenopus model organism knowledgebase, Xenbase, refactoring data ingestion pipelines and modifying the user interface to adapt to multispecies echinoderm content. This approach leveraged over 15 years of previous database and web application development to generate a new fully featured informatics resource in a single year. In addition to the software stack, Echinobase uses the private cloud and physical hosts that support Xenbase. Echinobase currently supports six echinoderm species, focused on those used for genomics, developmental biology and gene regulatory network analyses. Over 38 000 gene pages, 18 000 publications, new improved genome assemblies, JBrowse genome browser and BLAST + services are available and supported by the development of a new echinoderm anatomical ontology, uniformly applied formal gene nomenclature, and consistent orthology predictions. A novel feature of Echinobase is integrating support for multiple, disparate species. New genomes from the diverse echinoderm phylum will be added and supported as data becomes available. The common code development design of the integrated knowledgebases ensures parallel improvements as each resource evolves. This approach is widely applicable for developing new model organism informatics resources.

Synthesis, In Silico Study, and In Vitro Antifungal Activity of New 5-(1,3-Diphenyl-1H-Pyrazol-4-yl)-4-Tosyl-4,5-Dihydrooxazoles.

The increase in multi-drug resistant Candida strains has caused a sharp rise in life-threatening fungal infections in immunosuppressed patients, including those with SARS-CoV-2. Novel antifungal drugs are needed to combat multi-drug-resistant yeasts. This study aimed to synthesize a new series of 2-oxazolines and evaluate the ligands in vitro for the inhibition of six Candida species and in silico for affinity to the CYP51 enzymes (obtained with molecular modeling and protein homology) of the same species. The 5-(1,3-diphenyl-1H-pyrazol-4-yl)-4-tosyl-4,5-dihydrooxazoles 6a-j were synthesized using the Van Leusen reaction between 1,3-diphenyl-4-formylpyrazoles 4a-j and TosMIC 5 in the presence of K2CO3 or KOH without heating, resulting in short reaction times, high compound purity, and high yields. The docking studies revealed good affinity for the active site of the CYP51 enzymes of the Candida species in the following order: 6a-j > 4a-j > fluconazole (the reference drug). The in vitro testing of the compounds against the Candida species showed lower MIC values for 6a-j than 4a-j, and for 4a-j than fluconazole, thus correlating well with the in silico findings. According to growth rescue assays, 6a-j and 4a-j (like fluconazole) inhibit ergosterol synthesis. The in silico toxicity assessment evidenced the safety of compounds 6a-j, which merit further research as possible antifungal drugs.

Bionanomining: bioengineered CuO nanoparticles from mining and organic waste for photo-catalytic dye degradation.

The novel bioengineered CuO nanoparticles were successfully synthesized directly using green chemistry, the nontoxic and renewable aqueous extract of waste papaya peel (Carica papaya) as a precursor. The XRD analysis indicated a monoclinic phase of CuO nanoparticles and a size of 20 nm, and the optical absorption analysis showed a peak in the 264 nm range. In TEM, the morphology of the NPs was observed to be almost spherical with a particle size of 15 nm. The CuO nanoparticles showed good efficiency in the degradation of methylene, obtaining up to 50% in 40 min using 6 mg in 60 ml of MB at 10 mg/L. The novel presented in this work derives from using rock minerals, from which we have directly obtained copper salt and copper oxide nanoparticles. This process not only utilizes ecological green chemistry but also offers an economic advantage by directly producing nanoparticles from the mineral instead of purchasing costly pure chemical reagents and employing novel nanomaterials to purify wastewater.

Quasi-Diamond Platelet-Shaped Zinc Oxide Nanostructures Display Enhanced Antibacterial Activity.

The current study compares the antibacterial activity of zinc oxide nanostructures (neZnO). For this purpose, two bacterial strains, Escherichia coli (ATCC 4157) and Staphylococcus aureus (ATCC 29213) were challenged in room light conditions with the aforementioned materials. Colloidal and hydrothermal methods were used to obtain the quasi-round and quasi-diamond platelet-shape nanostructures. Thus, the oxygen vacancy (VO ) effects on the surface of neZnO are also considered to assess its effects on antibacterial activity. The neZnO characterization was achieved by X-ray diffraction (XRD), a selected area electron diffraction (SAED) and Raman spectroscopy. The microstructural effects were monitored by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Furthermore, optical absorption ultraviolet visible spectrophotometry (UV-Vis) and X-ray photoelectron spectroscopy (XPS) analyses complement the physical characterization of these nanostructures; neZnO caused 50 % inhibition (IC50 ) at concentrations from 0.064 to 0.072 mg/mL for S. aureus and from 0.083 to 0.104 mg/mL for E. coli, indicating an increase in activity against S. aureus compared to E. coli. Consequently, quasi-diamond platelet-shaped nanostructures (average particle size of 377.6±10 nm) showed enhanced antibacterial activity compared to quasi-round agglomerated particles (average size of 442.8±12 nm), regardless of Vo presence or absence.

Artificial sweeteners and cardiovascular risk.

PURPOSE OF REVIEW: Globalization and the increase in consumption of ultra-processed foods have led to a need for greater knowledge on the health impacts of certain nutrients such as artificial sweeteners. This review aims to analyse the role of artificial sweeteners (nutritive and nonnutritive) and their impact on cardiometabolic and cardiovascular disease (CVD) risk. RECENT FINDINGS: The detrimental effects of a high-calorie, high-sugar diet have been well established. In light of this, health authorities recommend limiting sugar consumption. This has led the food industry to develop different artificial sweeteners with specific properties, such as flavour and stability (nutritive artificial sweeteners: NAS), and others aimed at limiting sugar in the diet (nonnutritive artificial sweeteners: nNAS). Likewise, recent evidence explores the influence of artificial sweeteners (NAS and nNAS) on CVD risk through risk factors such as obesity and type 2 diabetes mellitus, among others. SUMMARY: This review aims to provide an updated overview of the impact of NAS and nNAS on cardiovascular health and provide recommendations regarding their consumption.

Synthesis of Fluorescent Pyrrolo[1,2-a]pyrimidines from Fischer Carbene Complexes as Building Blocks.

A novel synthetic methodology is reported for the synthesis of fluorescent pyrrolo[1,2-a]pyrimidines. Fischer carbene complexes served as the synthetic platform for (3+3) cyclization to form the heterocyclic moiety. The reaction process furnished two products, their ratio being modulated by the metal, base, and solvent. The selectivity exhibited was studied by analyzing the potential energy surface with density functional theory tools. The photophysical properties of absorption and emission were also evaluated. The dyes absorbed at wavelengths of 240-440 nm, depending on the substituents. The maximum emission wavelength was in the range of 470-513 nm, with quantum yields of 0.36-1.0 and a high Stokes shift range of 75-226 nm.

Liver resection versus radiofrequency ablation in octogenarian patients for hepatocellular carcinoma: a propensity score multicenter analysis.

BACKGROUND: Liver resection (LR) and radiofrequency ablation (RFA) are considered curative options for hepatocellular carcinoma (HCC). The aim of this study was to compare outcomes after LR and RFA in octogenarian patients with HCC. MATERIALS AND METHODS: This multicenter retrospective study included 102 elderly patients (> 80 years old) treated between January 2009 and January 2019, who underwent LR or RFA for HCC (65 and 37 with, respectively). RESULTS: After Propensity Score Matching, the postoperative course of LR was burdened by a higher rate of complications than RFA group (64% vs 14%, respectively, p: 0.001). The LR group had also significantly longer operative time (207 ± 85 min vs 33 ± 49 min, p < 0.001) and postoperative hospital stays than the RFA group (7 d vs 2 d, p = 0.019). Overall survival at 1-, 2-, and 3-year were 86%, 86%, and 70% for the LR group and 82%, 64%, and 52% for the RFA group (p = 0.380). Disease-free survival at 1-, 2-, and 3-year were 89%, 74%, and 56% for the LR group, and 51%, 40%, and 40% for the RFA group (p = 0.037). CONCLUSION: Despite a higher rate of Dindo-Clavien I-II post-operative complications, a longer operative time and length of hospital stay, LR in octogenarian patients can provide comparable 90d mortality than RFA and better long-term outcomes.

Higher independent mobility to school among adolescents: A secondary analysis using cross-sectional data between 2010 and 2017 in Spanish youth.

AIM: To describe and to analyse the associations between independent mobility to school (IM) with gender and age in Spanish youth aged 6-18 years old from 2010 to 2017. Moreover, to study the changes in the rates of IM from 2010 to 2017 by gender and age. METHODS: Cross-sectional data were obtained from 11 Spanish studies. The study sample comprised 3460 children and 1523 adolescents. Logistic regressions models (IM with gender and age) and multilevel logistic regressions (IM with time period) were used. RESULTS: Boys had higher odds ratio (OR) of IM than girls in children (OR = 1.86; CI: 1.50-2.28, p < 0.01). Adolescents showed higher IM than children: 12-14 years old (OR: 6.30; CI: 1.65-23.97) and 14-16 years old (OR: 7.33; CI: 1.18-45.39) had higher IM than 6-8 years old for boys (all, p < 0.05). Moreover, 12-14 years old (OR: 4.23; CI: 1.01-17.81) had higher IM than 6-8 years old for girls (p < 0.001). IM was not associated with the time period. CONCLUSION: The IM is higher in boys and in adolescents, highlighting the relevance to promote IM strategies targeting girls and children. In these strategies is essential the support of researchers, public health practitioners and families to achieve positive results.

Quantum Entanglement and State-Transference in Fenna-Matthews-Olson Complexes: A Post-Experimental Simulation Analysis in the Computational Biology Domain.

Fenna-Mathews-Olson complexes participate in the photosynthetic process of Sulfur Green Bacteria. These biological subsystems exhibit quantum features which possibly are responsible for their high efficiency; the latter may comprise multipartite entanglement and the apparent tunnelling of the initial quantum state. At first, to study these aspects, a multidisciplinary approach including experimental biology, spectroscopy, physics, and math modelling is required. Then, a global computer modelling analysis is achieved in the computational biology domain. The current work implements the Hierarchical Equations of Motion to numerically solve the open quantum system problem regarding this complex. The time-evolved states obtained with this method are then analysed under several measures of entanglement, some of them already proposed in the literature. However, for the first time, the maximum overlap with respect to the closest separable state is employed. This authentic multipartite entanglement measure provides information on the correlations, not only based on the system bipartitions as in the usual analysis. Our study has led us to note a different view of FMO multipartite entanglement as tiny contributions to the global entanglement suggested by other more basic measurements. Additionally, in another related trend, the initial state, considered as a Förster Resonance Energy Transfer, is tracked using a novel approach, considering how it could be followed under the fidelity measure on all possible permutations of the FMO subsystems through its dynamical evolution by observing the tunnelling in the most probable locations. Both analyses demanded significant computational work, making for a clear example of the complexity required in computational biology.

Pyrrole-Based Enaminones as Building Blocks for the Synthesis of Indolizines and Pyrrolo[1,2-a]pyrazines Showing Potent Antifungal Activity.

As a new approach, pyrrolo[1,2-a]pyrazines were synthesized through the cyclization of 2-formylpyrrole-based enaminones in the presence of ammonium acetate. The enaminones were prepared with a straightforward method, reacting the corresponding alkyl 2-(2-formyl-1H-pyrrol-1-yl)acetates, 2-(2-formyl-1H-pyrrol-1-yl)acetonitrile, and 2-(2-formyl-1H-pyrrol-1-yl)acetophenones with DMFDMA. Analogous enaminones elaborated from alkyl (E)-3-(1H-pyrrol-2-yl)acrylates were treated with a Lewis acid to afford indolizines. The antifungal activity of the series of substituted pyrroles, pyrrole-based enaminones, pyrrolo[1,2-a]pyrazines, and indolizines was evaluated on six Candida spp., including two multidrug-resistant ones. Compared to the reference drugs, most test compounds produced a more robust antifungal effect. Docking analysis suggests that the inhibition of yeast growth was probably mediated by the interaction of the compounds with the catalytic site of HMGR of the Candida species.

Non-Local Parallel Processing and Database Settlement Using Multiple Teleportation Followed by Grover Post-Selection.

Quantum information applications emerged decades ago, initially introducing a parallel development that mimicked the approach and development of classical computer science. However, in the current decade, novel computer-science concepts were rapidly extended to the fields of quantum processing, computation, and communication. Thus, areas such as artificial intelligence, machine learning, and neural networks have their quantum versions; furthermore, the quantum brain properties of learning, analyzing, and gaining knowledge are discussed. Quantum properties of matter conglomerates have been superficially explored in such terrain; however, the settlement of organized quantum systems able to perform processing can open a new pathway in the aforementioned domains. In fact, quantum processing involves certain requisites as the settlement of copies of input information to perform differentiated processing developed far away or in situ to diversify the information stored there. Both tasks at the end provide a database of outcomes with which to perform either information matching or final global processing with at least a subset of those outcomes. When the number of processing operations and input information copies is large, parallel processing (a natural feature in quantum computation due to the superposition) becomes the most convenient approach to accelerate the database settlement of outcomes, thus affording a time advantage. In the current study, we explored certain quantum features to realize a speed-up model for the entire task of processing based on a common information input to be processed, diversified, and finally summarized to gain knowledge, either in pattern matching or global information availability. By using superposition and non-local properties, the most valuable features of quantum systems, we realized parallel local processing to set a large database of outcomes and subsequently used post-selection to perform an ending global processing or a matching of information incoming from outside. We finally analyzed the details of the entire procedure, including its affordability and performance. The quantum circuit implementation, along with tentative applications, were also discussed. Such a model could be operated between large processing technological systems using communication procedures and also on a moderately controlled quantum matter conglomerate. Certain interesting technical aspects involving the non-local control of processing via entanglement were also analyzed in detail as an associated but notable premise.

Diet and vascular risk.

PURPOSE OF REVIEW: The basis for the prevention and treatment of cardiovascular disease (CVD) inevitably involves lifestyle modification, including dietary pattern (DP). The aim of this review is to address the different models of healthy DP with their peculiarities and nutritional components as well as their importance in the management of CVD. RECENT FINDINGS: Classical cardiovascular risk factors such as hypertension, dyslipidaemia and diabetes are strongly influenced by diet and physical activity. However, current evidence supports the role of emerging risk factors such as inflammatory status, oxidative stress and endothelial function in the development of CVD. Likewise, recent evidence explores how healthy DP can modulate CVD risk through these risk factors. SUMMARY: Although the Mediterranean diet (MedDiet) is the paradigm of the healthy DP in the light of current scientific evidence, there are other DP that we should be aware of due to their results in epidemiological studies, randomized clinical trials (RCTs) and meta-analyses on CVD risk modulation. The best-analysed DP are the MedDiet, Dietary Approaches to Stop Hypertension (DASH), the Nordic DP, the Vegetarian DP, the Portfolio DP, the Low-carbohydrate DP and the Planetary Health diet initiative.

Divergent Pd-catalyzed Functionalization of 4-Oxazolin-2-ones and 4-Methylene-2-oxazolidinones and Synthesis of Heterocyclic-Fused Indoles.

Palladium-catalyzed functionalization was presently performed on two building blocks: 4-oxazolin-2-ones and 4-methylene-2-oxazolidinones. Direct Heck arylation of 4-oxazolin-2-ones led to a series of 5-aryl-4-oxazolin-2-ones, including analogues with N-chiral auxiliary, in an almost quantitative yield. The Pd(II)-catalyzed homocoupling reaction of 4-oxazolin-2-ones provided novel heterocyclic across-ring dienes. Meanwhile, the intramolecular cross-coupling of N-aryl-4-methylene-2-oxazolidinones furnished a series of oxazolo[3,4-a]indol-3-ones. Further functionalization of 4-methylene-2-oxazolidinones afforded substituted indoles and heterocyclic-fused indoles with aryl, bromo, carbinol, formyl, and vinyl groups. A computational study was carried out to account for the behavior of the formylated derivatives. The currently developed methodology was applied to a new formal total synthesis of ellipticine.

Cascade synthesis of indolizines and pyrrolo[1,2-a]pyrazines from 2-formyl-1-propargylpyrroles.

A straightforward synthesis of indolizines and pyrrolo[1,2-a]pyrazines was performed through a cascade condensation/cyclization/aromatization reaction of substituted 2-formyl-N-propargylpyrroles with active methylene compounds such as nitromethane, alkyl malonates, methyl cyanoacetate and malononitrile. Under basic conditions, the reaction proceeded satisfactorily to provide the corresponding 6,7-disubstituted indolizines. The condensation of the pyrrolic analogues with ammonium acetate gave rise to pyrrolo[1,2-a]pyrazines in high yields. N-Allenyl-2-formylpyrroles behaved as more reactive substrates than 2-formyl-N-propargylpyrroles, furnishing the expected indolizines in higher yields. Hence, an allenyl-containing intermediate was probably generated as the reactive species in the reaction mechanism of some N-propargyl pyrroles prior to the cyclization reaction.

Optofluidic real-time cell sorter for longitudinal CTC studies in mouse models of cancer.

Circulating tumor cells (CTCs) play a fundamental role in cancer progression. However, in mice, limited blood volume and the rarity of CTCs in the bloodstream preclude longitudinal, in-depth studies of these cells using existing liquid biopsy techniques. Here, we present an optofluidic system that continuously collects fluorescently labeled CTCs from a genetically engineered mouse model (GEMM) for several hours per day over multiple days or weeks. The system is based on a microfluidic cell sorting chip connected serially to an unanesthetized mouse via an implanted arteriovenous shunt. Pneumatically controlled microfluidic valves capture CTCs as they flow through the device, and CTC-depleted blood is returned back to the mouse via the shunt. To demonstrate the utility of our system, we profile CTCs isolated longitudinally from animals over 4 days of treatment with the BET inhibitor JQ1 using single-cell RNA sequencing (scRNA-Seq) and show that our approach eliminates potential biases driven by intermouse heterogeneity that can occur when CTCs are collected across different mice. The CTC isolation and sorting technology presented here provides a research tool to help reveal details of how CTCs evolve over time, allowing studies to credential changes in CTCs as biomarkers of drug response and facilitating future studies to understand the role of CTCs in metastasis.

Quantification of glycated hemoglobin and glucose in vivo using Raman spectroscopy and artificial neural networks.

Undiagnosed type 2 diabetes (T2D) remains a major public health concern. The global estimation of undiagnosed diabetes is about 46%, being this situation more critical in developing countries. Therefore, we proposed a non-invasive method to quantify glycated hemoglobin (HbA1c) and glucose in vivo. We developed a technique based on Raman spectroscopy, RReliefF as a feature selection method, and regression based on feed-forward artificial neural networks (FFNN). The spectra were obtained from the forearm, wrist, and index finger of 46 individuals. The use of FFNN allowed us to achieve an error in the predictive model of 0.69% for HbA1c and 30.12 mg/dL for glucose. Patients were classified according to HbA1c values into three categories: healthy, prediabetes, and T2D. The proposed method obtained a specificity and sensitivity of 87.50% and 80.77%, respectively. This work demonstrates the benefit of using artificial neural networks and feature selection techniques to enhance Raman spectra processing to determine glycated hemoglobin and glucose in patients with undiagnosed T2D.

Germline pathogenic variants in Mexican patients with hereditary triple-negative breast cancer.

OBJECTIVE: Describe the prevalence of breast cancer (BC)- associated germline pathogenic variants (PVs) among Mexican patients with triple-negative BC (TNBC). MATERIALS AND METHODS: The spectrum of PVs identified among patients with TNBC who were enrolled in a prospective registry and underwent genetic testing was analyzed. RESULTS: Of 387 patients with invasive TNBC and a median age at diagnosis of 39 years (range 21-72), 113 (29%) were carriers of PVs in BC-susceptibility genes: BRCA1 (79%), BRCA2 (15%), and other (6%: ATM, BRIP1, PALB2, PTEN, RAD51C, and TP53). PV carriers were younger at BC diagnosis (37 vs. 40 years, p=0.004) than non-carriers. CONCLUSION: A large proportion of TNBC in Mexican patients is associated with germline PVs, the vast majority in BRCA. The incremental yield of PVs in other BC-susceptibility genes was modest, and a stepwise approach starting with BRCA testing may be justified if it is more cost-effective than multigene panel testing.

Crossroads in Liver Transplantation: Is Artificial Intelligence the Key to Donor-Recipient Matching?

Liver transplantation outcomes have improved in recent years. However, with the emergence of expanded donor criteria, tools to better assist donor-recipient matching have become necessary. Most of the currently proposed scores based on conventional biostatistics are not good classifiers of a problem that is considered "unbalanced." In recent years, the implementation of artificial intelligence in medicine has experienced exponential growth. Deep learning, a branch of artificial intelligence, may be the answer to this classification problem. The ability to handle a large number of variables with speed, objectivity, and multi-objective analysis is one of its advantages. Artificial neural networks and random forests have been the most widely used deep classifiers in this field. This review aims to give a brief overview of D-R matching and its evolution in recent years and how artificial intelligence may be able to provide a solution.

Cancer control in Latin America and the Caribbean: recent advances and opportunities to move forward.

The increasing burden of cancer represents a substantial problem for Latin America and the Caribbean. Two Lancet Oncology Commissions in 2013 and 2015 highlighted potential interventions that could advance cancer care in the region by overcoming existing challenges. Areas requiring improvement included insufficient investment in cancer control, non-universal health coverage, fragmented health systems, inequitable concentration of cancer services, inadequate registries, delays in diagnosis or treatment initiation, and insufficient palliative services. Progress has been made in key areas but remains uneven across the region. An unforeseen challenge, the COVID-19 pandemic, strained all resources, and its negative effect on cancer control is expected to continue for years. In this Series paper, we summarise progress in several aspects of cancer control since 2015, and identify persistent barriers requiring commitment of additional resources to reduce the cancer burden in Latin America and the Caribbean.

Fischer Carbene Complexes: A Glance at Two Decades of Research on Higher-Order Cycloaddition Reactions.

The structure of Fischer carbene complexes (FCCs) is electron deficient. If bearing an α,ß-unsaturated system, it can generate a wide variety of compounds by undergoing many different transformations, including higher-order cycloadditions. The latter are described as pericyclic reactions in which more than six electrons participate. These reactions have been employed in various areas of organic synthesis, resulting in highly selective compounds with a broad range of scaffolds. The first studies on higher-order cycloadditions involving FCCs frequently yielded competing byproducts. Many groups have attempted to increase selectivity by exploring distinct reaction conditions, reagents and co-catalysts (e. g., metal-mediated cycloadditions). The present review is the first to focus exclusively on using higher-order cycloadditions involving FCCs to synthesize carbocycles and heterocycles. Based on two decades of reports, an analysis is made of the main aspects of the mechanisms proposed for higher-order cycloadditions and the structural diversity obtained by the substituent effect.