Bismuthene - Tetrahedral DNA nanobioconjugate for virus detection.

In this work, we present an electrochemical sensor for fast, low-cost, and easy detection of the SARS-CoV-2 spike protein in infected patients. The sensor is based on a selected combination of nanomaterials with a specific purpose. A bioconjugate formed by Few-layer bismuthene nanosheets (FLB) and tetrahedral DNA nanostructures (TDNs) is immobilized on Carbon Screen-Printed Electrodes (CSPE). The TDNs contain on the top vertex an aptamer that specifically binds to the SARS-CoV-2 spike protein, and a thiol group at the three basal vertices to anchor to the FLB. The TDNs are also marked with a redox indicator, Azure A (AA), which allows the direct detection of SARS-CoV-2 spike protein through changes in the current intensity of its electrolysis before and after the biorecognition reaction. The developed sensor can detect SARS-CoV-2 spike protein with a detection limit of 1.74 fg mL-1 directly in nasopharyngeal swab human samples. Therefore, this study offers a new strategy for rapid virus detection since it is versatile enough for different viruses and pathogens.

Prenatal inflammation remodels lung immunity and function by programming ILC2 hyperactivation.

Here, we examine how prenatal inflammation shapes tissue function and immunity in the lung by reprogramming tissue-resident immune cells from early development. Maternal, but not fetal, type I interferon-mediated inflammation provokes expansion and hyperactivation of group 2 innate lymphoid cells (ILC2s) seeding the developing lung. Hyperactivated ILC2s produce increased IL-5 and IL-13 and are associated with acute Th2 bias, decreased Tregs, and persistent lung eosinophilia into adulthood. ILC2 hyperactivation is recapitulated by adoptive transfer of fetal liver precursors following prenatal inflammation, indicative of developmental programming at the fetal progenitor level. Reprogrammed ILC2 hyperactivation and subsequent lung immune remodeling, including persistent eosinophilia, is concomitant with worsened histopathology and increased airway dysfunction equivalent to papain exposure, indicating increased asthma susceptibility in offspring. Our data elucidate a mechanism by which early-life inflammation results in increased asthma susceptibility in the presence of hyperactivated ILC2s that drive persistent changes to lung immunity during perinatal development.

Anatomical factors of the maxillary tuberosity that influence molar distalization.

Objective: To examine the areas of the maxillary tuberosity (MT) (coronal, apical, width, and height) with respect to the presence or absence of the third molar to establish possible anatomical limitations for molar distalization. Methods: A total of 277 tuberosities were evaluated through sagittal computed tomography (CT) images, divided for measurement into coronal (free of bone), apical (area of influence of the maxillary sinus), and tuberosity (bony area) zones, and stratified by the presence or absence of the third molar, sex, and two age subgroups. Mann-Whitney U test was used to compare the groups considering the third molar. Results: The medians of the width and height of the tuberosity decreased significantly in the absence of the third molar (P < 0.001). The apical area also showed differences, with negative values in the absence of the third molar and positive values in the presence of the third molar (P < 0.001). However, no differences were observed for the coronal area (P > 0.05). Conclusions: In the absence of the third molar, the size of the MT, represented by its width and height, was smaller and negative values (decrease) were observed for the maxillary sinus. The sagittal CT provides useful information regarding the amount of bone tissue available for distalization and relationship of the second molar with respect to the maxillary sinus, which allows individualizing each case in relation to the amount and type of movement expected.

Prevalence of Myofascial Trigger Points in Isolated Idiopathic Cervical Dystonia: A Possible Contributor to Pain, Movement and Disability.

BACKGROUND: Myofascial trigger points (TrPs) are hypersensitive points located in a tight band of muscle that, when palpated, produce not only local pain but also referred (distant) pain. The role of TrPs in patients with cervical dystonia (CD) has not been investigated. OBJECTIVE: To identify the presence of TrPs in patients with isolated idiopathic CD and their association with pain. METHODS: Thirty-one patients (74.2% women; age: 61.2 years, SD: 10.1 years) participated. TrPs were explored in the sternocleidomastoid, upper trapezius, splenius capitis, levator scapulae, anterior scalene, suboccipital, and infraspinatus muscles. Clinical features of CD were documented as well as the presence of pain. The severity of dystonia and its consequences were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). RESULTS: The mean number of TrPs for each patient was 12 (SD:3), with no differences between patients with pain (n = 20) and those without pain (n = 11). Active TrPs were only found in patients with pain (mean: 7.5, SD:4). Latent TrPs were found in both groups but were more prevalent (P < 0.001) in patients without pain (mean: 11, SD:3.5) than in those with pain (mean: 5, SD:3.5). The number of active TrPs or latent TrPs was positively associated with the TWSTRS disability subscale and the TWSTRS total score. The number of active, but not latent, TrPs was associated with worse scores on the TWSTRS pain subscale. CONCLUSION: Active TrPs were present in patients with CD reporting pain, while latent TrPs were present in all CD patients, irrespective of their pain status. The numbers of active/latent TrPs were associated with disability. TrPs could act as pain generators in CD and also contribute to the involuntary muscle contractions characteristic of dystonia.

A multimodal framework for extraction and fusion of satellite images and public health data.

In low- and middle-income countries, the substantial costs associated with traditional data collection pose an obstacle to facilitating decision-making in the field of public health. Satellite imagery offers a potential solution, but the image extraction and analysis can be costly and requires specialized expertise. We introduce SatelliteBench, a scalable framework for satellite image extraction and vector embeddings generation. We also propose a novel multimodal fusion pipeline that utilizes a series of satellite imagery and metadata. The framework was evaluated generating a dataset with a collection of 12,636 images and embeddings accompanied by comprehensive metadata, from 81 municipalities in Colombia between 2016 and 2018. The dataset was then evaluated in 3 tasks: including dengue case prediction, poverty assessment, and access to education. The performance showcases the versatility and practicality of SatelliteBench, offering a reproducible, accessible and open tool to enhance decision-making in public health.

Dopamine-derived pigments in nature: Identification of decarboxybetalains in Amaranthaceae species.

A unique family of decarboxylated betalains derived from dopamine has recently been discovered. Due to the lack of chemical standards, the existence and distribution of decarboxylated betalains in nature remains unknown. Traditional betalains contain L-DOPA as the starting point of the biosynthetic pathway and betalamic acid as a structural and functional unit, while the recently discovered betalains rely on dopamine. Here, 30 dopamine-derived betalains were biotechnologically produced, purified, and characterized, creating an unprecedented library to explore their properties and presence in nature. The maximum absorbance wavelengths for the pigments ranged between 461nm and 485 nm. HPLC analysis showed retention times between 0.6-2.2 min higher than traditional betalains due to their higher hydrophobicity. The presence of decarboxybetalains in nature was screened using HPLC-ESI-Q-TOF mass spectrometry in various species of the Amaranthaceae family: beetroot (Beta vulgaris subsp. vulgaris), Swiss chard (B. vulgaris var. cicla), celosia (Celosia argentea var. plumosa) and quinoa (Chenopodium quinoa). The latter species had the highest content of decarboxybetalains (28 compounds in its POEQ-143 variety). 29 pigments were found distributed among the different analyzed plant sources. The abundance of decarboxybetalains demonstrated in this work highlights these pigments as an important family of phytochemicals in the order Caryophyllales.

Padlocking dihydrofurannulation for the control of small degree of helicity built on a fused-tetracyclic core.

Enantioselective construction of small molecules displaying a configurationally stable helical shape built on a fused-tetracyclic core is a daunting synthetic challenge even more pronounced when five-membered rings are incorporated in the structure. The resulting higher configurational lability strongly hampers their access, and therefore the development of new efficient methodologies is timely and highly desirable. In this context, we describe a padlocking approach via the enantioselective organocatalytic domino furannulation of appropriately designed achiral fused-tricyclic precursors resulting in the synthesis of configurationally locked helically chiral tetracyclic scaffolds featuring one or two five-membered rings with the simultaneous control of central and helical chiralities.

Neonatal Vitamin D and Associations with Longitudinal Changes of Eczema up to 25 Years of Age.

BACKGROUND: Early-life vitamin D is a potentially modifiable risk factor for the development of eczema, but there is a lack of data on longitudinal associations. METHOD: We measured 25(OH)D3 levels from neonatal dried blood spots in 223 high-allergy-risk children. Latent class analysis was used to define longitudinal eczema phenotype up to 25 years (4 subclasses). Skin prick tests (SPTs) to 6 allergens and eczema outcomes at 6 time points were used to define eczema/sensitization phenotypes. Associations between 25(OH)D3 and prevalent eczema and eczema phenotypes were assessed using logistic regression models. RESULTS: Median 25(OH)D3 level was 32.5 nmol/L (P25-P75 = 23.1 nmol/L). Each 10 nmol/L increase in neonatal 25(OH)D3 was associated with a 26% reduced odds of early-onset persistent eczema (adjusted multinomial odds ratio (aMOR) = 0.74, 95% CI = 0.56-0.98) and 30% increased odds of early-onset-resolving eczema (aMOR = 1.30, 95% CI = 1.05-1.62) when compared to minimal/no eczema up to 12 years. Similar associations were seen for eczema phenotype up to 25 years. We did not see any strong evidence for the association between neonatal 25(OH)D3 and prevalent eczema or eczema/sensitization phenotype. CONCLUSIONS: Higher neonatal 25(OH)D3 levels, a reflection of maternal vitamin D levels in pregnancy, may reduce the risk of early-onset persistent eczema.

DF-DM: A foundational process model for multimodal data fusion in the artificial intelligence era.

In the big data era, integrating diverse data modalities poses significant challenges, particularly in complex fields like healthcare. This paper introduces a new process model for multimodal Data Fusion for Data Mining, integrating embeddings and the Cross-Industry Standard Process for Data Mining with the existing Data Fusion Information Group model. Our model aims to decrease computational costs, complexity, and bias while improving efficiency and reliability. We also propose "disentangled dense fusion," a novel embedding fusion method designed to optimize mutual information and facilitate dense inter-modality feature interaction, thereby minimizing redundant information. We demonstrate the model's efficacy through three use cases: predicting diabetic retinopathy using retinal images and patient metadata, domestic violence prediction employing satellite imagery, internet, and census data, and identifying clinical and demographic features from radiography images and clinical notes. The model achieved a Macro F1 score of 0.92 in diabetic retinopathy prediction, an R-squared of 0.854 and sMAPE of 24.868 in domestic violence prediction, and a macro AUC of 0.92 and 0.99 for disease prediction and sex classification, respectively, in radiological analysis. These results underscore the Data Fusion for Data Mining model's potential to significantly impact multimodal data processing, promoting its adoption in diverse, resource-constrained settings.

Rapid and simple viral protein detection by functionalized 2D MoS2/graphene electrochemiluminescence aptasensor.

In this work we present the development of an electrochemiluminescence aptasensor based on electrografting molybdenum disulphide nanosheets functionalized with diazonium salt (MoS2-N2+) upon screen-printed electrodes of graphene (SPEs GPH) for viral proteins detection. In brief, this aptasensor consists of SPEs GPH electrografted with MoS2-N2+ and modified with a thiolated aptamer, which can specifically recognize the target protein analyte. In this case, we have used SARS-CoV-2 spike protein as model protein. Electrochemiluminescence detection was performed by using the [Ru(bpy)3]2+/TPRA (tripropylamine) system, which allows the specific detection of the SARS-CoV-2 spike protein easily and rapidly with a detection limit of 9.74 fg/mL and a linear range from 32.5 fg/mL to 50.0 pg/mL. Moreover, the applicability of the aptasensor has been confirmed by the detection of the protein directly in human saliva samples. Comparing our device with a traditional saliva antigen test, our aptasensor can detect the spike protein even when the saliva antigen test gives a negative result.

Sensitization-Associated Symptoms and Neuropathic-like Features in Patients with Cervical Dystonia and Pain.

Background: This exploratory study evaluated the presence of sensitization-associated and neuropathic-like symptoms and identified their association with pressure sensitivity, pain, and disability in patients with cervical dystonia (CD). Methods: Thirty-one patients with CD (74.2% women, age: 61.2 years, SD 10.1) participated. Data collected included clinical variables, the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), the Central Sensitization Inventory (CSI), the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI), as well as widespread pressure pain thresholds (PPTs). Results: Patients with CD with pain (n = 20, 64.5%) showed higher scores on the TWSTRS disability subscale and the CSI (p < 0.001), and lower PPTs (p < 0.05). Fifteen patients (15/31, 48%) showed sensitization-associated symptoms (CSI ≥ 40), whereas five of the patients with pain (5/20, 25%) exhibited neuropathic-like symptoms (S-LANSS ≥ 12). The CSI and S-LANSS were positively associated with the TWSTRS, HADS-A and HADS-D, and negatively associated with PPTs. HADS-D and S-LANSS explained 72.5% of the variance of the CSI (r2: 0.725), whereas CSI explained 42.3% of the variance of the S-LANSS (r2: 0.423). Conclusions: Pain is an important source of disability in CD, and may be a consequence of different mechanisms, including sensitization.

The Human Health Impacts of the Red Imported Fire Ant in the Western Pacific Region Context: A Narrative Review.

Background: The red imported fire ant (RIFA) is one of the world's most destructive invasive species. RIFA stings are painful and can lead to allergic reactions, including life-threatening anaphylaxis, yet health impacts remain inadequately defined. Methods: We searched MEDLINE (Ovid) and Google Scholar (grey literature) from inception until 20 September 2023 for articles in English using search terms related to red imported fire ants and allergies, including anaphylaxis. Results: Approximately a third of the population in RIFA-infested areas are stung each year. The most frequent reaction is a sterile 1-2 mm pseudo pustule on the skin. Approximately 20% of stings cause a large local reaction and between about 0.5% and 2% stings cause a systemic allergic reaction which can range from skin symptoms to life-threatening anaphylaxis. Local biodiversity is also significantly disrupted by invading RIFA and may lead to complex adverse effects on human health, from agriculture losses to expanded ranges for pathogen vectors. Conclusions: The potential for red imported fire ants to establish themselves as an invasive species in the Western Pacific presents a substantial and costly health issue. Successful eradication and surveillance programs, to identify and eradicate new incursions, would avoid substantial health impacts and costs.

Virtual reality and augmented reality in medical education: an umbrella review.

Objective: This umbrella review aims to ascertain the extent to which immersive Virtual Reality (VR) and Augmented Reality (AR) technologies improve specific competencies in healthcare professionals within medical education and training, in contrast to traditional educational methods or no intervention. Methods: Adhering to PRISMA guidelines and the PICOS approach, a systematic literature search was conducted across major databases to identify studies examining the use of VR and AR in medical education. Eligible studies were screened and categorized based on the PICOS criteria. Descriptive statistics and chi-square tests were employed to analyze the data, supplemented by the Fisher test for small sample sizes or specific conditions. Analysis: The analysis involved cross-tabulating the stages of work (Development and Testing, Results, Evaluated) and variables of interest (Performance, Engagement, Performance and Engagement, Effectiveness, no evaluated) against the types of technologies used. Chi-square tests assessed the associations between these categorical variables. Results: A total of 28 studies were included, with the majority reporting increased or positive effects from the use of immersive technologies. VR was the most frequently studied technology, particularly in the "Performance" and "Results" stages. The chi-square analysis, with a Pearson value close to significance (p = 0.052), suggested a non-significant trend toward the association of VR with improved outcomes. Conclusions: The results indicate that VR is a prevalent tool in the research landscape of medical education technologies, with a positive trend toward enhancing educational outcomes. However, the statistical analysis did not reveal a significant association, suggesting the need for further research with larger sample sizes. This review underscores the potential of immersive technologies to enhance medical training yet calls for more rigorous studies to establish definitive evidence of their efficacy.

Unraveling the Complex Interactions: Machine Learning Approaches to Predict Bacterial Survival against ZnO and Lanthanum-Doped ZnO Nanoparticles.

The rise in antibiotic-resistant bacteria is a global health challenge. Due to their unique properties, metal oxide nanoparticles show promise in addressing this issue. However, optimizing these properties requires a deep understanding of complex interactions. This study incorporated data-driven machine learning to predict bacterial survival against lanthanum-doped ZnO nanoparticles. The effect of incorporation of lanthanum ions on ZnO was analyzed. Even with high lanthanum concentration, no significant variations in structural, morphological, and optical properties were observed. The antibacterial activity of La-doped ZnO nanoparticles against Gram-positive and Gram-negative bacteria was qualitatively and quantitatively evaluated. Nanoparticles induce 60%, 95%, and 55% bacterial death against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, respectively. Algorithms such as Multilayer Perceptron, K-Nearest Neighbors, Gradient Boosting, and Extremely Random Trees were used to predict the bacterial survival percentage. Extremely Random Trees performed the best among these models with 95.08% accuracy. A feature relevance analysis extracted the most significant attributes to predict the bacterial survival percentage. Lanthanum content and particle size were irrelevant, despite what can be assumed. This approach offers a promising avenue for developing effective and tailored strategies to reduce the time and cost of developing antimicrobial nanoparticles.

Enhancing antioxidant properties of CeO2 nanoparticles with Nd3+ doping: structural, biological, and machine learning insights.

The antioxidant capabilities of nanoparticles are contingent upon various factors, including their shape, size, and chemical composition. Herein, novel Nd-doped CeO2 nanoparticles were synthesized and the neodymium content was varied to investigate the synergistic impact on the antioxidant properties of CeO2 nanoparticles. Incorporating Nd3+ induced changes in lattice parameters and significantly altered the morphology from nanoparticles to nanorods. The biological activity of Nd-doped CeO2 was examined against pathogenic bacterial strains, breast cancer cell lines, and antioxidant models. The antibacterial and anticancer activities of nanoparticles were not observed, which could be associated with the Ce3+/Ce4+ ratio. Notably, the incorporation of neodymium improved the antioxidant capacity of CeO2. Machine learning techniques were employed to forecast the antioxidant activity to enhance understanding and predictive capabilities. Among these models, the random forest model exhibited the highest accuracy at 96.35%, establishing it as a robust computational tool for elucidating the biological behavior of Nd-doped CeO2 nanoparticles. This study presents the first exploration of the influence of Nd3+ on the structural, optical, and biological attributes of CeO2, contributing valuable insights and extending the application of machine learning in predicting the therapeutic efficacy of inorganic nanomaterials.

Cabergoline as a Novel Strategy for Post-Pregnancy Breast Cancer Prevention in Mice and Human.

Post-pregnancy breast cancer often carries a poor prognosis, posing a major clinical challenge. The increasing trend of later-life pregnancies exacerbates this risk, highlighting the need for effective chemoprevention strategies. Current options, limited to selective estrogen receptor modulators, aromatase inhibitors, or surgical procedures, offer limited efficacy and considerable side effects. Here, we report that cabergoline, a dopaminergic agonist, reduces the risk of breast cancer post-pregnancy in a Brca1/P53-deficient mouse model, with implications for human breast cancer prevention. We show that a single dose of cabergoline administered post-pregnancy significantly delayed the onset and reduced the incidence of breast cancer in Brca1/P53-deficient mice. Histological analysis revealed a notable acceleration in post-lactational involution over the short term, characterized by increased apoptosis and altered gene expression related to ion transport. Over the long term, histological changes in the mammary gland included a reduction in the ductal component, decreased epithelial proliferation, and a lower presence of recombinant Brca1/P53 target cells, which are precursors of tumors. These changes serve as indicators of reduced breast cancer susceptibility. Additionally, RNA sequencing identified gene expression alterations associated with decreased proliferation and mammary gland branching. Our findings highlight a mechanism wherein cabergoline enhances the protective effect of pregnancy against breast cancer by potentiating postlactational involution. Notably, a retrospective cohort study in women demonstrated a markedly lower incidence of post-pregnancy breast cancer in those treated with cabergoline compared to a control group. Our work underscores the importance of enhancing postlactational involution as a strategy for breast cancer prevention, and identifies cabergoline as a promising, low-risk option in breast cancer chemoprevention. This strategy has the potential to revolutionize breast cancer prevention approaches, particularly for women at increased risk due to genetic factors or delayed childbirth, and has wider implications beyond hereditary breast cancer cases.

Lanthanide-Doped ZnO Nanoparticles: Unraveling Their Role in Cytotoxicity, Antioxidant Capacity, and Nanotoxicology.

This study used a sonochemical synthesis method to prepare (La, Sm)-doped ZnO nanoparticles (NPs). The effect of incorporating these lanthanide elements on the structural, optical, and morphological properties of ZnO-NPs was analyzed. The cytotoxicity and the reactive oxygen species (ROS) generation capacity of ZnO-NPs were evaluated against breast (MCF7) and colon (HT29) cancer cell lines. Their antioxidant activity was analyzed using a DPPH assay, and their toxicity towards Artemia salina nauplii was also evaluated. The results revealed that treatment with NPs resulted in the death of 10.559-42.546% and 18.230-38.643% of MCF7 and HT29 cells, respectively. This effect was attributed to the ability of NPs to downregulate ROS formation within the two cell lines in a dose-dependent manner. In the DPPH assay, treatment with (La, Sm)-doped ZnO-NPs inhibited the generation of free radicals at IC50 values ranging from 3.898 to 126.948 µg/mL. Against A. salina nauplii, the synthesized NPs did not cause death nor induce morphological changes at the tested concentrations. A series of machine learning (ML) models were used to predict the biological performance of (La, Sm)-doped ZnO-NPs. Among the designed ML models, the gradient boosting model resulted in the greatest mean absolute error (MAE) (MAE 9.027, R2 = 0.86). The data generated in this work provide innovative insights into the influence of La and Sm on the structural arrangement and chemical features of ZnO-NPs, together with their cytotoxicity, antioxidant activity, and in vivo toxicity.

Transcriptome Analysis in Mexican Adults with Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) represents around 25% of adult acute leukemias. Despite the increasing improvement in the survival rate of ALL patients during the last decade, the heterogeneous clinical and molecular features of this malignancy still represent a major challenge for treatment and achieving better outcomes. To identify aberrantly expressed genes in bone marrow (BM) samples from adults with ALL, transcriptomic analysis was performed using Affymetrix Human Transcriptome Array 2.0 (HTA 2.0). Differentially expressed genes (DEGs) (±2-fold change, p-value < 0.05, and FDR < 0.05) were detected using the Transcriptome Analysis Console. Gene Ontology (GO), Database for Annotation, Visualization, and Integrated Discovery (DAVID), and Ingenuity Pathway Analysis (IPA) were employed to identify gene function and define the enriched pathways of DEGs. The protein-protein interactions (PPIs) of DEGs were constructed. A total of 871 genes were differentially expressed, and DNTT, MYB, EBF1, SOX4, and ERG were the top five up-regulated genes. Meanwhile, the top five down-regulated genes were PTGS2, PPBP, ADGRE3, LUCAT1, and VCAN. An association between ERG, CDK6, and SOX4 expression levels and the probability of relapse and death was observed. Regulation of the immune system, immune response, cellular response to stimulus, as well as apoptosis signaling, inflammation mediated by chemokines and cytokines, and T cell activation were among the most altered biological processes and pathways, respectively. Transcriptome analysis of ALL in adults reveals a group of genes consistently associated with hematological malignancies and underscores their relevance in the development of ALL in adults.

Linking QKD Testbeds across Europe.

Quantum-key-distribution (QKD) networks are gaining importance and it has become necessary to analyze the most appropriate methods for their long-distance interconnection. In this paper, four different methods of interconnecting remote QKD networks are proposed. The methods are used to link three different QKD testbeds in Europe, located in Berlin, Madrid, and Poznan. Although long-distance QKD links are only emulated, the methods used can serve as a blueprint for the secure interconnection of distant QKD networks in the future. Specifically, the presented approaches combine, in a transparent way, different fiber and satellite physical media, as well as common standards of key delivery interfaces. The testbed interconnections are designed to increase the security by utilizing multipath techniques and multiple hybridizations of QKD and post-quantum cryptography (PQC) algorithms.