Binding and sensing diverse small molecules using shape-complementary pseudocycles.

We describe an approach for designing high-affinity small molecule-binding proteins poised for downstream sensing. We use deep learning-generated pseudocycles with repeating structural units surrounding central binding pockets with widely varying shapes that depend on the geometry and number of the repeat units. We dock small molecules of interest into the most shape complementary of these pseudocycles, design the interaction surfaces for high binding affinity, and experimentally screen to identify designs with the highest affinity. We obtain binders to four diverse molecules, including the polar and flexible methotrexate and thyroxine. Taking advantage of the modular repeat structure and central binding pockets, we construct chemically induced dimerization systems and low-noise nanopore sensors by splitting designs into domains that reassemble upon ligand addition.

Efficacy of alendronic acid solution in removal calcium hydroxide from root canals.

Background: Intracanal medication is considered an alternative after instrumentation in the case of pulp necrosis. However, the elimination of this medication plays an important role in the obturation process, which is why various chelating solutions have currently been studied for this purpose. Therefore, this study aimed to analyze the irrigant based on alendronic acid (AA), which contains in its chemical structure functional groups capable of forming complexes with Ca2+ ions. Material and Methods: 90 single-rooted teeth were crowned and standardized to a length of 13 mm. They were instrumented with a progressive K file (Dentsply Maillefer) from #15 to #30. Ca(OH)2 was placed as intracanal medication for 7 days. The roots were randomly divided into the following 4 experimental groups (n=13) according to the irrigant used: 2.25% NaClO, calcium suspension, 0.22% AA, and 10% citric acid; as well as negative (n=5; saline solution) and positive controls (n=5, 17% EDTA). The roots were divided longitudinally and the % of permeable dentinal tubules (% PDT) was determined by thirds (cervical, middle and apical), by analyzing the micrographs obtained by scanning electron microscope (SEM) and the imageJ program. The quantification of the remaining Ca2+ was determined using the Arsenazo III technique. Results: The Kruskal Wallis test was used for the % of permeable dentinal tubules where a significant difference was determined for the different thirds (p<0.005). In the apical third, citric acid and AA irrigants presented a median of 17.71 and 17.51 % PDT respectively. In relation to the quantification of the remaining total calcium, the lowest value was found with AA with a concentration of 4.83 mmol/L. Conclusions: The 0.22% AA solution has the same capacity to remove Ca(OH)2 from the root canal walls as 17% EDTA and 10% citric acid. Key words:Alendronic acid, calcium hydroxide, citric acid, EDTA, irrigant solution,root canal.

Mixed-methods analysis of satisfaction during a 12-session mindfulness-based intervention for women with a substance use disorder and trauma symptomatology.

Satisfaction with an intervention influences the uptake of behavior changes and the long-term efficacy of the intervention. Therefore, it is crucial to assess satisfaction by participant profile when creating and adapting behavior interventions for minoritized populations. Qualitative and quantitative data on participant trauma symptom severity and intervention satisfaction were collected through self-report surveys from 54 women. The sample was 59.3% Hispanic, with an average age of 33.21 (SD = 10.42), who were in residential treatment for substance use disorders (SUDs) and participated in a 12-session mindfulness-based intervention. Qualitative responses were coded using thematic analysis, and an integrative mixed-methods approach was used to compare qualitative theme frequency between high-trauma (N = 28) and low-trauma (N = 26) groups at session 2 and session 11. High- and low-trauma groups were determined by interquartile ranges (bottom 25% = low; top 75% = high). In session 2, the low-trauma group reported significantly higher satisfaction (M = 4.20, SD = 0.55) than the high-trauma group (M = 3.77, SD = 0.89); t(43) = 1.90, p = 0.03. In session 11, there was no significant difference between groups. The mixed-methods analysis revealed that "trouble focusing" appeared more frequently in the high-trauma group than in the low-trauma group during session 2, but the theme was not present in either group at session 11, suggesting that this might pose an initial barrier for individuals with high trauma but subsides as the intervention progresses. This speaks to the importance of retention strategies tailored for participants with SUDs and high trauma while they adjust to the intervention. Assessing initial challenges with satisfaction may help facilitators intervene to increase participant satisfaction.

Strategy for the analysis of lignocellulosic biomass to select a viable transformation route in the Colombian context.

Lignocellulosic biomass is widely available in the world. However, a consensus has yet to be established to evaluate the biomass valorization alternatives. The chemical composition is the primary technical limitation in selecting a transformation route to obtain value-added products. In this paper, the bagasse from non-centrifuged sugar (NCS) production and Pinus patula (PP) wood chips were analyzed in terms of complete chemical composition to establish their potential for selecting the transformation routes. A strategy to select the best route based on the chemical composition was applied and a feedstock criteria model was proposed. Schemes were obtained and compared using a bioprocess selection strategy proposed in previous works. As a result, the preliminary biorefinery schemes were finally defined. The assessment of schemes derived from the outlined strategy included technical, economic, environmental, and social analyses. The environmental evaluation was complemented with a geolocation assessment, revealing a 0.75-ton CO2-eq/yr contribution to the carbon footprint for local distribution. The sustainability index for the PP biorefinery and the bagasse from NCS production was analyzed, resulting in indices of 44.8 and 60.9, respectively. These values were primarily derived from the economic and environmental analyses of both processes.

Abiotic processes control carbon dioxide dynamics in temperate karst lakes.

Inland waters are crucial in the carbon cycle, contributing significantly to the global CO2 fluxes. Carbonate lakes may act as both sources and sinks of CO2 depending on the interactions between the amount of dissolved inorganic carbon (DIC) inputs, lake metabolisms, and geochemical processes. It is often difficult to distinguish the dominant mechanisms driving CO2 dynamics and their effects on CO2 emissions. This study was undertaken in three groundwater-fed carbonate-rich lakes in central Spain (Ruidera Lakes), severely polluted with nitrates from agricultural overfertilization. Diel and seasonal (summer and winter) changes in CO2 concentration (CCO2) DIC, and CO2 emissions-(FCO2)-, as well as physical and chemical variables, including primary production and phytoplanktonic chlorophyll-a were measured. In addition, δ13C-DIC, δ13C-CO2 in lake waters, and δ13C of the sedimentary organic matter were measured seasonally to identify the primary CO2 sources and processes. While the lakes were consistently CCO2 supersaturated and FCO2 was released to the atmosphere during both seasons, the highest CCO2 and DIC were in summer (0.36-2.26 µmol L-1). Our results support a strong phosphorus limitation for primary production in these lakes, which impinges on CO2 dynamics. External DIC inputs to the lake waters primarily drive the CCO2 and, therefore, the FCO2. The δ13C-DIC signatures below -12‰  confirmed the primary geogenic influence on DIC. As also suggested by the high values on the calcite saturation index, the Miller-Tans plot revealed that the CO2 source in the lakes was close to the signature provided by the fractionation of δ13C-CO2 from calcite precipitation. Therefore, the main contribution behind the CCO2 values found in these karst lakes should be attributed to the calcite precipitation process, which is temperature-dependent according to the seasonal change observed in δ13C-DIC values. Finally, co-precipitation of phosphate with calcite could partly explain the observed low phytoplankton production in these lakes and the impact on the contribution to increasing greenhouse gas emissions. However, as eutrophication increases and the soluble reactive phosphorus (SRP) content increases, the co-precipitation of phosphate is expected to be progressively inhibited. These thresholds must be assessed to understand how the CO32- ions drive lake co-precipitation dynamics. Carbonate regions extend over 15% of the Earth's surface but seem essential in the CO2 dynamics at a global scale.

Atomically accurate de novo design of single-domain antibodies.

Despite the central role that antibodies play in modern medicine, there is currently no way to rationally design novel antibodies to bind a specific epitope on a target. Instead, antibody discovery currently involves time-consuming immunization of an animal or library screening approaches. Here we demonstrate that a fine-tuned RFdiffusion network is capable of designing de novo antibody variable heavy chains (VHH's) that bind user-specified epitopes. We experimentally confirm binders to four disease-relevant epitopes, and the cryo-EM structure of a designed VHH bound to influenza hemagglutinin is nearly identical to the design model both in the configuration of the CDR loops and the overall binding pose.

Recent Latinx immigrants to Miami/Dade County (FL): Travel patterns before, during, and one year after the COVID-19 pandemic lockdown.

INTRODUCTION: Understanding the transportation needs of immigrants is crucial for the design and promotion of safe, equitable, and sustainable living environments. This study examines the transportation patterns from a sample of Recent Latinx Immigrants (RLIs) upon arrival to Miami/Dade Co (MDC), Florida. METHODS: Collected between 2018 and 2021, data came from a longitudinal study examining drinking and driving trajectories among 540 RLIs to MDC. Retrospective pre-immigration data (T0) were obtained simultaneously with the first-year post-immigration data (T1). Follow up surveys were conducted one year later, before (T2-BC) or during a pandemic lockout (T2-DC), and two years later (T3). Descriptive and repeated measures mixed-model regression were used to examine the data. RESULTS: Driving declined from T0 to T1, although remained higher than previously reported for other locations. Not having a valid driver's license was the main reason for the decline. The initial reduction in driving was paralleled by an increase in the use of transit, riding as passengers in private vehicles, and walking. A year later (T2), as RLIs' income and access to a driver's license grew, driving rates increased (even during the pandemic lockdown), while the use of other transportation modes decreased. A year after the pandemic lockdown (T3), driving as well as the use of other transportation modes receded. Reasons for this decline are unclear. CONCLUSIONS: RLIs reported elevated driving rates upon their arrival to MDC. The COVID-19 pandemic seems to have altered the RLIs' transportation patterns, provoking an overall decline in mobility that lasted even after the pandemic lockdown ceased. PRACTICAL APPLICATIONS: Transportation planners working on developing safe and equitable transportation systems in MDC should: (1) identify and address barriers to the use of transportation modes other than driving by RLIs; and (2) understand reasons for the broad decline in transportation modes after the pandemic lockdown.

Remotely Controlled Electrochemical Degradation of Metallic Implants.

Biodegradable medical implants promise to benefit patients by eliminating risks and discomfort associated with permanent implantation or surgical removal. The time until full resorption is largely determined by the implant's material composition, geometric design, and surface properties. Implants with a fixed residence time, however, cannot account for the needs of individual patients, thereby imposing limits on personalization. Here, an active Fe-based implant system is reported whose biodegradation is controlled remotely and in situ. This is achieved by incorporating a galvanic cell within the implant. An external and wireless signal is used to activate the on-board electronic circuit that controls the corrosion current between the implant body and an integrated counter electrode. This configuration leads to the accelerated degradation of the implant and allows to harvest electrochemical energy that is naturally released by corrosion. In this study, the electrochemical properties of the Fe-30Mn-1C/Pt galvanic cell model system is first investigated and high-resolution X-ray microcomputed tomography is used to evaluate the galvanic degradation of stent structures. Subsequently, a centimeter-sized active implant prototype is assembled with conventional electronic components and the remotely controlled corrosion is tested in vitro. Furthermore, strategies toward the miniaturization and full biodegradability of this system are presented.

Somatic Mutations in Latin American Breast Cancer Patients: A Systematic Review and Meta-Analysis.

(1) Background: Somatic mutations may be connected to the exposome, potentially playing a role in breast cancer's development and clinical outcomes. There needs to be information regarding Latin American women specifically, as they are underrepresented in clinical trials and have limited access to somatic analysis in their countries. This study aims to systematically investigate somatic mutations in breast cancer patients from Latin America to gain a better understanding of tumor biology in the region. (2) Methods: We realize a systematic review of studies on breast cancer in 21 Latin American countries using various databases such as PubMed, Google Scholar, Web of Science, RedAlyc, Dianlet, and Biblioteca Virtual en Salud. Of 392 articles that fit the criteria, 10 studies have clinical data which can be used to create a database containing clinical and genetic information. We compared mutation frequencies across different breast cancer subtypes using statistical analyses and meta-analyses of proportions. Furthermore, we identified overexpressed biological processes and canonical pathways through functional enrichment analysis. (3) Results: 342 mutations were found in six Latin American countries, with the TP53 and PIK3CA genes being the most studied mutations. The most common PIK3CA mutation was H1047R. Functional analysis provided insights into tumor biology and potential therapies. (4) Conclusion: evaluating specific somatic mutations in the Latin American population is crucial for understanding tumor biology and determining appropriate treatment options. Combining targeted therapies may improve clinical outcomes in breast cancer. Moreover, implementing healthy lifestyle strategies in Latin America could enhance therapy effectiveness and clinical outcomes.

Effect of HKUST-1 metal-organic framework in root and shoot systems, as well as seed germination.

The seed germination, as well as root and shoot growth effect of HKUST-1 MOF, and its derived linear polymer ([Cu2(OH)(BTC)(H2O)]n·2nH2O) were herein examined. These effects were studied for seven higher plant species: sweet corn (Zea mays L.), black bean (Phaseolus vulgaris L.), tomato (Solanum lycopersicum L.), lettuce (Lactuca sativa L.), celosia (Celosia argentea L.), Aztec marigold (Tagetes erecta L.), and gypsophila (Gypsophila paniculata L.). The studied concentrations of MOFs were 10, 100, 500, or 1000 mg/L, enhancing the percentage of germination and growth of plants in most species. In general, the growth of the root is lower compared to the controls due to the capacity of the MOF to adsorb water and provide micronutrients such as C, O, and Cu, acting as a reserve for the plant. Shoot system growths are more pronounced with HKUST-1 compared with control, and linear polymer, due to the 3D structure adsorbs major water contents. It was found that all studied species are tolerant not only to Cu released from the material, but more evident to Cu structured in MOFs, and this occurs at high concentrations compared to many other systems. Finally, copper fixation was not present, studied by EDX mapping, banning the possibility of metallic phytotoxicity to the tested cultivars.

3D nanofabricated soft microrobots with super-compliant picoforce springs as onboard sensors and actuators.

Microscale organisms and specialized motile cells use protein-based spring-like responsive structures to sense, grasp and move. Rendering this biomechanical transduction functionality in an artificial micromachine for applications in single-cell manipulations is challenging due to the need for a bio-applicable nanoscale spring system with a large and programmable strain response to piconewton-scale forces. Here we present three-dimensional nanofabrication and monolithic integration, based on an acrylic elastomer photoresist, of a magnetic spring system with quantifiable compliance sensitive to 0.5 pN, constructed with customized elasticity and magnetization distributions at the nanoscale. We demonstrate the effective design programmability of these 'picospring' ensembles as energy transduction mechanisms for the integrated construction of customized soft micromachines, with onboard sensing and actuation functions at the single-cell scale for microrobotic grasping and locomotion. The integration of active soft springs into three-dimensional nanofabrication offers an avenue to create biocompatible soft microrobots for non-disruptive interactions with biological entities.

Magnetotactic Sperm Cells for Assisted Reproduction.

Biohybrid micromotors are active microscopic agents consisting of biological and synthetic components that are being developed as novel tools for biomedical applications. By capturing motile sperm cells within engineered microstructures, they can be controlled remotely while being propelled forward by the flagellar beat. This makes them an interesting tool for reproductive medicine that can enable minimally invasive sperm cell delivery to the oocyte in vivo, as a treatment for infertility. The generation of sperm-based micromotors in sufficiently large numbers, as they are required in biomedical applications has been challenging, either due to the employed fabrication techniques or the stability of the microstructure-sperm coupling. Here, biohybrid micromotors, which can be assembled in a fast and simple process using magnetic microparticles, are presented. These magnetotactic sperm cells show a high motility and swimming speed and can be transferred between different environments without large detrimental effects on sperm motility and membrane integrity. Furthermore, clusters of micromotors are assembled magnetically and visualized using dual ultrasound (US)/photoacoustic (PA) imaging. Finally, a protocol for the scaled-up assembly of micromotors and their purification for use in in vitro fertilization (IVF) is presented, bringing them closer to their biomedical implementation.

A qualitative community health assessment of HIV prevention awareness in a semi-rural Latinx seasonal farm working community in South Florida.

This article explores HIV awareness and prevention in a Latinx seasonal farmworker community of south Miami-Dade County in the USA. The study took place as part of a larger community assessment that aimed to determine community needs and resources related to substance abuse, violence and HIV in the Latinx seasonal farmworker communities of south Miami-Dade County, with a particular focus on fathers' and their male sons' relationships. The study collected data on HIV knowledge and prevention, healthcare-seeking behaviours, cultural norms, and communication barriers about HIV prevention between fathers and sons. Data were collected through in-depth interviews with community leaders, two focus groups with social and health services providers, and four focus groups involving fathers and their adolescent sons. A deductive approach to data analysis was undertaken. Five major themes were identified: (1) HIVrelated knowledge and perception; (2) HIV prevention strategies; (3) barriers and needs for tailored preventive health and care services in the community; (4) stress over sex-related communication; and (5) the dominance of traditional masculine gender norms in the household and the community.

Perceived Stress and Depressive Symptoms Among Recent Latino/a Immigrants: The Moderating Effects of Emotion Regulation and Dispositional Mindfulness.

Their initial years in the U.S. can be stressful for recent Latino/a immigrants (RLIs). This study examines the association between perceived stress and depressive symptoms and the moderating effect of emotion regulation and dispositional mindfulness. Cross-sectional data from an ongoing longitudinal study of RLIs was used. Hierarchical multiple regression analyses were performed to examine simple main effects of the predictor variables on depressive symptoms. The study also tested the moderating effects of emotion regulation and dispositional mindfulness on the association between perceived stress and depressive symptoms. Greater perceived stress and cognitive reappraisal were associated with greater depressive symptoms. Lower levels of appraisal and higher levels of non-reactivity mindfulness strengthened the association between perceived stress and depressive symptoms. Findings can inform the development of culturally tailored interventions that account for distinct aspects of emotion regulation and dispositional mindfulness associated with managing stress and decreasing depressive symptoms among RLIs.

Leveraging the adolescent brain cognitive development study to advance and promote adolescent health: Introduction to the special issue.

The empirical reports in this special issue of Health Psychology showcase the work of a diverse array of accomplished early-stage investigators who are members of the Adolescent Brain Cognitive Development (ABCD) study consortium and who are drawn from the community of female and underrepresented scientists. Their studies focus primarily on youth assessed during preadolescence and early adolescence, and they are based on the ABCD data that were available to the scientific community at the time this special issue was being prepared (e.g., baseline, Years 1 and 2 assessments). They address a variety of questions about adolescent health behavior, such as the effects of screen time and caffeine on sleep; individual lifestyle, neighborhood, and environmental factors associated with physical health conditions and brain development; and the antecedents and consequences of prenatal and adolescent substance exposure. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Acculturative Orientations Among Hispanic/Latinx Caregivers in the ABCD Study: Associations With Caregiver and Youth Mental Health and Youth Brain Function.

Background: Population-based neuroscience offers opportunities to examine important but understudied sociocultural factors such as acculturation. Acculturation refers to the extent to which an individual retains their cultural heritage and/or adopts the receiving society's culture and is particularly salient among Hispanic/Latinx immigrants. Specific acculturative orientations have been linked to vulnerability to substance use, depression, and suicide and are known to influence family dynamics between caregivers and their children. Methods: Using data from first- and second-generation Hispanic/Latinx caregivers in the Adolescent Brain Cognitive Development (ABCD) Study (N = 1057), we examined how caregivers' acculturative orientation affects their mental health, as well as the mental health and brain function of their children. Neuroimaging analyses focused on regions associated with self- and affiliation-based social processing (ventromedial prefrontal cortex, insula, and temporoparietal junction). Results: We identified 2 profiles of caregiver acculturation: bicultural (retains heritage culture while adopting U.S. culture) and detached (discards heritage culture and rejects U.S. culture). Bicultural caregivers exhibited fewer internalizing and externalizing problems than detached caregivers; furthermore, youth exhibited similar internalizing effects across caregiver profiles. In addition, youth with bicultural caregivers displayed increased resting-state brain activity (i.e., fractional amplitude of low-frequency fluctuations and regional homogeneity) in the left insula, which has been linked to psychopathology; however, differences in long-range functional connectivity were not significant. Conclusions: Caregiver acculturation is an important familial factor that has been linked to significant differences in youth mental health and insula activity. Future work should examine sociocultural and neurodevelopmental changes across adolescence to assess health outcomes and determine whether localized, corticolimbic brain effects are ultimately translated into long-range connectivity differences.

Aminopeptidase N/CD13 Crosslinking Promotes the Activation and Membrane Expression of Integrin CD11b/CD18.

The ß2 integrin CD11b/CD18, also known as complement receptor 3 (CR3), and the moonlighting protein aminopeptidase N (CD13), are two myeloid immune receptors with overlapping activities: adhesion, migration, phagocytosis of opsonized particles, and respiratory burst induction. Given their common functions, shared physical location, and the fact that some receptors can activate a selection of integrins, we hypothesized that CD13 could induce CR3 activation through an inside-out signaling mechanism and possibly have an influence on its membrane expression. We revealed that crosslinking CD13 on the surface of human macrophages not only activates CR3 but also influences its membrane expression. Both phenomena are affected by inhibitors of Src, PLCγ, Syk, and actin polymerization. Additionally, after only 10 min at 37 °C, cells with crosslinked CD13 start secreting pro-inflammatory cytokines like interferons type 1 and 2, IL-12p70, and IL-17a. We integrated our data with a bioinformatic analysis to confirm the connection between these receptors and to suggest the signaling cascade linking them. Our findings expand the list of features of CD13 by adding the activation of a different receptor via inside-out signaling. This opens the possibility of studying the joint contribution of CD13 and CR3 in contexts where either receptor has a recognized role, such as the progression of some leukemias.

The challenge of adequately reporting preeclampsia for epidemiological surveillance: An example from a referral center in a middle-income country.

Adequately reporting of preeclampsia is a challenge. The aim of this study was to compare the diagnosis of preeclampsia based on clinical and laboratory findings and ICD-10 codes (International Classification of Diseases) at admission and discharge in a referral center, over a one-year period. Among 2,839 women admitted for childbirth, 208 presented confirmed preeclampsia, based on chart audits. Among these, 77.4% at admission presented ICD-10 codes assigned as hypertension, and 47.1% at discharge. In 14.4% of confirmed preeclampsia, ICD-10 codes for hypertension were not used. Adequate reporting of preeclampsia is key for clinical surveillance, counselling and guiding public health interventions.

The Impact of HIV-Related Stigma on Racial/Ethnic Disparities in Retention in HIV Care Among Adults Living with HIV in Florida.

BACKGROUND: Our study examines the effects of distinct HIV stigma subtypes on retention in care and racial-ethnic differences among persons with HIV (PWH). METHODS: Using Florida Medical Monitoring Project 2015-2017 data, we analyzed patients' clinical and behavioral characteristics. We analyzed 89,889 PWH in Florida (50.0% non-Hispanic Blacks, 20.8% Hispanics, 29.2% non-Hispanic whites). HIV stigma subtypes, negative self-image, anticipated stigma, personalized stigma, and retention in care were examined with logistic regressions. RESULTS: People with high negative self-image and anticipated stigma were less likely to be retained (CI: 0.84-0.92; 0.47-0.53). The association between HIV-related stigma subtypes and retention in care differed between Black, White, and Hispanic participants. Negative self-image was associated with higher retention rates among Hispanics (CI: 5.64-9.26) and Whites (CI: 1.04-1.27), while low retention rates among Blacks (0.617-0.686). The likelihood of staying in care was lower across all racial-ethnic groups when the anticipated stigma was high or moderate. In contrast, personalized stigma increased retention across all racial-ethnic groups. CONCLUSION: Results showed that distinct types of HIV stigma differentially impact retention, and these associations differ by race and ethnicity. Future interventions should address the effect HIV stigma subtypes have on racially minoritized PWH retention.