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Abstract Vaccination has played a critical role in mitigating COVID-19. Despite the availability of licensed vaccines, there remains a pressing need for improved vaccine platforms that provide high protection, safety, and versatility, while also reducing vaccine costs. In response to these challenges, our aim is to create a self-adjuvanted vaccine against SARS-CoV-2, utilizing Virus-Like Particles (VLPs) as the foundation. To achieve this, we produced bacteriophage (Qβ) VLPs in a prokaryotic system and purified them using a rapid and cost-effective strategy involving organic solvents. This method aims to solubilize lipids and components of the cell membrane to eliminate endotoxins present in bacterial samples. For vaccine formulation, Receptor Binding Domain (RBD) antigens were conjugated using chemical crosslinkers, a process compatible with Good Manufacturing Practice (GMP) standards. Transmission Electron Microscopy (TEM) confirmed the expected folding and spatial configuration of the QβVLPs vaccine. Additionally, vaccine formulation assessment involved SDS-PAGE stained with Coomassie Brilliant Blue, Western blotting, and stereomicroscopic experiments. In vitro and in vivo evaluations of the vaccine formulation were conducted to assess its capacity to induce a protective immune response without causing side effects. Vaccine doses of 20 µg and 50 µg stimulated the production of neutralizing antibodies. In in vivo testing, the group of animals vaccinated with 50 µg of vaccine formulation provided complete protection against virus infection, maintaining stable body weight without showing signs of disease. In conclusion, the QβVLPs-RBD vaccine has proven to be effective and safe, eliminating the necessity for supplementary adjuvants and offering a financially feasible approach. Moreover, this vaccine platform demonstrates flexibility in targeting Variants of Concern (VOCs) via established conjugation protocols with VLPs.

Abstract The production of açaí seed waste from the commercial and extractive exploitation of the Euterpe oleraceae palm tree is a serious problem that contributes to environmental contamination and production of greenhouse gases, a fact that suggests the need for an environmentally correct destination for this waste produced on a large scale. To this end, this study was conducted to evaluate the potential of acaí seed biochar (BCA) in mitigating the toxic effects of copper in Brazilian mahogany plants, analyzing biometrics and gas exchange. The experimental design was in randomized blocks, with five blocks, in a 4 × 3 factorial scheme, corresponding to the control (without Cu) and three concentration of Cu (200, 400, and 600 mg Cu kg−1) and three levels of BCA (0%, 5% and 10%) proportional to the amount of soil in the pots, totaling sixty experimental units. The use of 5% BCA in soils contaminated with up to 200 mg kg−1 Cu promoted biometric increase (height, diameter, number of leaves), maintaining gas exchange (photosynthesis, stomatal conductance, transpiration, internal carbon and internal/external carbon), and consequently, maintaining water use efficiency in plants under abiotic stress, resulting in plant growth. The findings of this study allow us to indicate the use of biochar in remediating and improving the growth of plants grown in copper-contaminated soils. The production of biochar from açaí seeds is an ecologically sustainable alternative, because it reduces its accumulation on public roads and contributes to reducing soil pollution. In the context of public policies, biochar production could be a source of income in the context of the bioeconomy and circular economy practiced in the Amazon, because it is produced in large quantities.

Abstract Inherited retinal dystrophies/degenerations (IRDs) are the leading cause of visual impairment and incurable familial blindness in the Western world. Given the clinical and genetic heterogeneity, establishing a molecular diagnosis is especially relevant. The aim of this study was to perform the first nationwide survey to understand the prevalence and current management of IRDs in Portugal. A response was obtained from 26 healthcare providers (HCP) (76.5% response rate). Only 4 respondents reported not managing IRD patients. Most HCPs (68.1%) reported managing up to 100 patients, while three currently manage between 501 and 1000 patients. Based on the Portuguese population, an estimated IRD prevalence of 0.031%, i.e., about 1 in 3000 individuals, was calculated. In most HCPs (86.3%), most patients are adults, and non-syndromic retinitis pigmentosa is the most frequent diagnosis. Only 4 HCPs currently use the national, web-based IRD registry (IRD-PT). However, all but one respondent expressed interest in participating in such a registry. Genetic testing is available in 54.5%, with 58.3% HCPs reporting solved rates between 61–80%, but 4 to 9 months to get a genetic test result in 83.4% of cases. Based on this survey, the prevalence of biallelic RPE65-associated disease in Portugal is 0.00031%, i.e., approximately 1:300,000 individuals. Data from this study provide vital background information on national differences in the diagnosis and management of IRD patients. Nationwide implementation of the IRD-PT registry should be encouraged and supported to provide population-based reference data and to identify patients eligible for current and future therapies.

Abstract Generally, medicinal plants are harvested with high amount of water, so it is essential to subject the product to drying as soon as possible to prevent degradation before application. Most compounds from medicinal plants are sensitive to drying processes, so it is important to adjust the drying conditions. The objective of this study was to describe the drying of Rue (Ruta chalepensis L.) leaves, select the models that best fit each drying condition, determine the activation energy and thermodynamic properties of the leaves, and evaluate their quality after drying. Leaves were harvested with moisture content of 3.55 ± 0.05 kg water kg−1 dry matter and subjected to drying at temperatures of 40, 50, 60 and 70 °C. Valcam model showed the best fit to represent the drying kinetics of Rue leaves at temperatures of 40 and 70 °C, and Midilli model proved to be better for the temperatures of 50 and 60 °C. Effective diffusion coefficient increased linearly with the increase in drying air temperature, and the activation energy was 60.58 kJ mol−1. Enthalpy, entropy and Gibbs free energy values ranged from 57.973 to 57.723 kJ mol−1, from − 0.28538 to − 0.28614 kJ mol−1 K−1 and from 147.34 to 155.91 kJ mol−1, respectively, for the temperature range of 40–70 °C. Drying air temperature promoted darkening or tendency to loss of green color; increase in drying air temperature leads to greater discoloration, as well as a higher concentration of total phenolic compounds (about 221.10 mg GAE mL−1 g–1 dm), with a peak at temperature of 60 °C.

Abstract Acting as a goalkeeper in a video-game, a participant is asked to predict the successive choices of the penalty taker. The sequence of choices of the penalty taker is generated by a stochastic chain with memory of variable length. It has been conjectured that the probability distribution of the response times is a function of the specific sequence of past choices governing the algorithm used by the penalty taker to make his choice at each step. We found empirical evidence that besides this dependence, the distribution of the response times depends also on the success or failure of the previous prediction made by the participant. Moreover, we found statistical evidence that this dependence propagates up to two steps forward after the prediction failure.

Abstract Land subsidence rates in Mexico City reach 500 mm/year, causing progressive damage to the city’s core infrastructure, including the Metro system. A deadly overpass collapse in 2021, along a Metro line that had operated for less than 10 years, brought subsidence-related structural damage to the attention of the system’s authorities and led to major repairs to two of the twelve Metro lines. Still, the need for quantifying the magnitude and extent of subsidence affecting the Metro system’s widespread infrastructure prevails. Using a wealth of satellite radar interferometry observations, levelling surveys, subsurface profiles, linear gradient and differential displacement analyses, and structural-engineering parameters, we assess the vulnerability of the Metro system’s street-level and elevated segments to land subsidence. Our results reveal that high subsidence velocity gradients occur over sharp transitional zones between stable and fast-subsiding areas, reaching values of 1 $$\times \,10 ^{-3}$$ × 10 - 3 year $$^{-1}$$ - 1 , resulting in slope changes up to 3.5% over a 20-year period and differential displacements between columns. Our findings suggest locations where the consequences of subsidence have compromised the train’s braking safety design, increased railway flooding hazard, produced railway bending, and reduced the conceived 50-year service life of the Metro’s elevated overpasses.

Abstract The main objective of the present work was to highlight differences and similarities in gene expression patterns between different pluripotent stem cell cardiac differentiation protocols, using a workflow based on unsupervised machine learning algorithms to analyse the transcriptome of cells cultured as a 2D monolayer or as 3D aggregates. This unsupervised approach effectively allowed to portray the transcriptomic changes that occurred throughout the differentiation processes, with a visual representation of the entire transcriptome. The results allowed to corroborate previously reported data and also to unveil new gene expression patterns. In particular, it was possible to identify a correlation between low cardiomyocyte differentiation efficiencies and the early expression of a set of non-mesodermal genes, which can be further explored as predictive markers of differentiation efficiency. The workflow here developed can also be applied to analyse other stem cell differentiation transcriptomic datasets, envisaging future clinical implementation of cellular therapies.

Abstract Arm cycling is used for cardiorespiratory rehabilitation but its therapeutic effects on the neural control of the trunk after spinal cord injury (SCI) remain unclear. We investigated the effects of single session of arm cycling on corticospinal excitability, and the feasibility of home-based arm cycling exercise training on volitional control of the erector spinae (ES) in individuals with incomplete SCI. Using transcranial magnetic stimulation, we assessed motor evoked potentials (MEPs) in the ES before and after 30 min of arm cycling in 15 individuals with SCI and 15 able-bodied controls (Experiment 1). Both groups showed increased ES MEP size after the arm cycling. The participants with SCI subsequently underwent a 6-week home-based arm cycling exercise training (Experiment 2). MEP amplitudes and activity of the ES, and movements of the trunk during reaching, self-initiated rapid shoulder flexion, and predicted external perturbation tasks were measured. After the training, individuals with SCI reached further and improved trajectory of the trunk during the rapid shoulder flexion task, accompanied by increased ES activity and MEP amplitudes. Exercise adherence was excellent. We demonstrate preserved corticospinal drive after a single arm cycling session and the effects of home-based arm cycling exercise training on trunk function in individuals with SCI.

Abstract Staphylococcus pseudintermedius is an opportunistic pathogen causing a variety of infections that are difficult to treat, especially because of the development of antimicrobial resistance. It has a clonal distribution around the world. To have a better understanding of the MRSP population, we search the presence of MRSP in colonized or infected dogs. Samples from 99 dogs with infections and 35 from asymptomatic dogs were collected. Isolates were identified by mass spectrometry and Multiplex-PCR. The mecA gene was confirmed by conventional PCR. MRSP strains were analyzed by whole-genome sequencing. 75 S. pseudintermedius were identified, most from infection cases. The species were isolated from 70 out of the 135 dogs. Penicillin and Trimethoprim/Sulfamethoxazole presented higher resistance rates. Forty-seven strains were classified as multi-drug resistant (MDR), and were more isolated from dogs with infection (P

Abstract SARS-CoV-2 and its different variants caused a “wave and wave” pandemic pattern. During the first wave we demonstrated that standardized Brazilian green propolis extract (EPP-AF®) reduces length of hospital stay in adult patients with COVID-19. Afterwards, we decided to evaluate the impact of EPP-AF in hospitalized patients during the third wave of the pandemic. BeeCovid2 was a randomized, double-blind, placebo-controlled clinical trial in hospitalized COVID-19 adult patients. Patients were allocated to receive an oral dose of 900 mg/day of EPP-AF® or placebo for 10 days. The primary outcome was length of hospital stay. Secondary outcomes included safety, secondary infection rate, duration of oxygen therapy dependency, acute kidney injury and need for intensive care. Patients were followed up for 28 days after admission. We enrolled 188 patients; 98 were assigned to the propolis group and 90 to the placebo group. The post-intervention length of hospital stay was of 6.5 ± 6.0 days in the propolis group versus 7.7 ± 7.1 days in the control group (95% CI − 0.74 [− 1.94 to 0.42]; p = 0.22). Propolis did not have significant impact on the need for oxygen supplementation or frequency of AKI. There was a significant difference in the incidence of secondary infection between groups, with 6.1% in the propolis group versus 18.9% in the control group (95% CI − 0.28 [0.1–0.76], p = 0.01). The use of EPP-AF was considered safe and associated with a decrease in secondary infections. The drug was not associated with a significant reduction in length of hospital stay. ClinicalTrials.gov (NCT04800224).

Abstract Short-term increases in air pollution levels are linked to large adverse effects on health and productivity. However, existing regulatory monitoring systems lack the spatial or temporal resolution needed to capture localized events. This study uses a dense network of over 100 sensors, deployed across the city of Chicago, Illinois, to capture the spread of smoke from short-term structural fire events. Examining all large structural fires that occurred in the city over a year (N = 21), we characterize differences in PM $$_{2.5}$$ 2.5 concentrations downwind versus upwind of the fires. On average, we observed increases of up to 10.7 $$\upmu$$ μ g/m $$^{3}$$ 3 (95% CI 5.7–15.7) for sensors within 2 km and up to 7.7 $$\upmu$$ μ g/m $$^{3}$$ 3 (95% CI 3.4–12.0) for sensors 2–5 km downwind of fires. Statistically significant elevated concentrations were evident as far as 5 km downwind of the location of the fire and persisted over approximately 2 h on average. This work shows how low-cost sensors can provide insight on local and short-term pollution events, enabling regulators to provide timely warnings to vulnerable populations.

Abstract Brassica napus, a versatile crop with significant socioeconomic importance, serves as a valuable source of nutrition for humans and animals while also being utilized in biodiesel production. The expansion potential of B. napus is profoundly influenced by climatic variations, yet there remains a scarcity of studies investigating the correlation between climatic factors and its distribution. This research employs CLIMEX to identify the current and future ecological niches of B. napus under the RCP 8.5 emission scenario, utilizing the Access 1.0 and CNRM-CM5 models for the time frame of 2040–2059. Additionally, a sensitivity analysis of parameters was conducted to determine the primary climatic factors affecting B. napus distribution and model responsiveness. The simulated outcomes demonstrate a satisfactory alignment with the known current distribution of B. napus, with 98% of occurrence records classified as having medium to high climatic suitability. However, the species displays high sensitivity to thermal parameters, thereby suggesting that temperature increases could trigger shifts in suitable and unsuitable areas for B. napus, impacting regions such as Canada, China, Brazil, and the United States.

Abstract We introduce and validate four adaptive models (AMs) to perform a physiologically based Nested-Model-Selection (NMS) estimation of such microvascular parameters as forward volumetric transfer constant, Ktrans, plasma volume fraction, vp, and extravascular, extracellular space, ve, directly from Dynamic Contrast-Enhanced (DCE) MRI raw information without the need for an Arterial-Input Function (AIF). In sixty-six immune-compromised-RNU rats implanted with human U-251 cancer cells, DCE-MRI studies estimated pharmacokinetic (PK) parameters using a group-averaged radiological AIF and an extended Patlak-based NMS paradigm. One-hundred-ninety features extracted from raw DCE-MRI information were used to construct and validate (nested-cross-validation, NCV) four AMs for estimation of model-based regions and their three PK parameters. An NMS-based a priori knowledge was used to fine-tune the AMs to improve their performance. Compared to the conventional analysis, AMs produced stable maps of vascular parameters and nested-model regions less impacted by AIF-dispersion. The performance (Correlation coefficient and Adjusted R-squared for NCV test cohorts) of the AMs were: 0.914/0.834, 0.825/0.720, 0.938/0.880, and 0.890/0.792 for predictions of nested model regions, vp, Ktrans, and ve, respectively. This study demonstrates an application of AMs that quickens and improves DCE-MRI based quantification of microvasculature properties of tumors and normal tissues relative to conventional approaches.

Abstract Aluminium (Al)-rich palaeosols—i.e., palaeobauxite deposits—should have formed in karst depressions in carbonate sequences as a result of acidic solutions from oxidative weathering of sulfide minerals during the Great Oxidation Event (GOE), but no GOE-related karst-palaeobauxite deposits have so far been recorded. Here, we report results of in situ uranium–lead (U–Pb) dating of detrital zircon and spatially associated rutile from a metamorphosed Al-rich rock within a dolomite sequence in the Quadrilátero Ferrífero (QF) of Minas Gerais, Brazil, known as the Gandarela Formation. Rutile grains are highly enriched in thorium (Th = 3–46 ppm; Th/U ratio = 0.3–3.7) and yielded an isochron, lower-intercept age of ca. 2.12 Ga, which coincides with the final phase of the GOE—i.e., the Lomagundi event. The rutile age represents either authigenic growth of TiO2 enriched in Th, U and Pb during bauxite formation, or subsequent rutile crystallisation during metamorphic overprint. Both cases require an authigenic origin for the rutile. Its high Th contents can be used as a palaeoenvironmental indicator for decreased soil pH during the GOE. Our results also have implications for iron (Fe)-ore genesis in the QF. This study demonstrates that in situ U–Th–Pb-isotope analyses of rutile can place tight constraints on the age and nature of palaeosols.

Abstract During the past 15 years, new treatment paradigms for neovascular age-related macular degeneration (nvAMD) have evolved due to the advent of intravitreal anti-vascular endothelial growth factor (VEGF) therapy and rapid advances in retinal imaging. Recent publications describe eyes with type 1 macular neovascularization (MNV) as showing more resistance to macular atrophy than eyes with other lesion types. We sought to explore whether the perfusion status of the native choriocapillaris (CC) surrounding type 1 MNV influences its pattern of growth. To evaluate this effect, we analyzed a case series of 22 eyes from 19 nvAMD patients with type 1 MNV exhibiting growth on swept-source optical coherence tomography angiography (SS-OCTA) over a minimum follow-up of 12 months. We observed an overall weak correlation between type 1 MNV growth and CC flow deficits (FDs) average size (τ = 0.17, 95% CI [− 0.20, 0.62]) and a moderate correlation with CC FD % (τ = 0.21, 95% CI [− 0.16, 0.68]). Type 1 MNV was located beneath the fovea in most of the eyes (86%) and median visual acuity was 20/35 Snellen equivalent. Our results support that type 1 MNV recapitulates areas of CC blood flow impairment while serving to preserve foveal function.

Abstract The majority of early prediction scores and methods to predict COVID-19 mortality are bound by methodological flaws and technological limitations (e.g., the use of a single prediction model). Our aim is to provide a thorough comparative study that tackles those methodological issues, considering multiple techniques to build mortality prediction models, including modern machine learning (neural) algorithms and traditional statistical techniques, as well as meta-learning (ensemble) approaches. This study used a dataset from a multicenter cohort of 10,897 adult Brazilian COVID-19 patients, admitted from March/2020 to November/2021, including patients [median age 60 (interquartile range 48–71), 46% women]. We also proposed new original population-based meta-features that have not been devised in the literature. Stacking has shown to achieve the best results reported in the literature for the death prediction task, improving over previous state-of-the-art by more than 46% in Recall for predicting death, with AUROC 0.826 and MacroF1 of 65.4%. The newly proposed meta-features were highly discriminative of death, but fell short in producing large improvements in final prediction performance, demonstrating that we are possibly on the limits of the prediction capabilities that can be achieved with the current set of ML techniques and (meta-)features. Finally, we investigated how the trained models perform on different hospitals, showing that there are indeed large differences in classifier performance between different hospitals, further making the case that errors are produced by factors that cannot be modeled with the current predictors.

Abstract Crocodilians are a taxonomic group of large predators with important ecological and evolutionary benefits for ecosystem functioning in the face of global change. Anthropogenic actions affect negatively crocodilians’ survival and more than half of the species are threatened with extinction worldwide. Here, we map and explore three dimensions of crocodilian diversity on a global scale. To highlight the ecological importance of crocodilians, we correlate the spatial distribution of species with the ecosystem services of nutrient retention in the world. We calculate the effectiveness of global protected networks in safeguarding crocodilian species and provide three prioritization models for conservation planning. Our results show the main hotspots of ecological and evolutionary values are in southern North, Central and South America, west-central Africa, northeastern India, and southeastern Asia. African species have the highest correlation to nutrient retention patterns. Twenty-five percent of the world’s crocodilian species are not significantly represented in the existing protected area networks. The most alarming cases are reported in northeastern India, eastern China, and west-central Africa, which include threatened species with low or non-significant representation in the protected area networks. Our highest conservation prioritization model targets southern North America, east-central Central America, northern South America, west-central Africa, northeastern India, eastern China, southern Laos, Cambodia, and some points in southeastern Asia. Our research provides a global prioritization scheme to protect multiple dimensions of crocodilian diversity for achieving effective conservation outcomes.

Abstract The objective of this study was to verify the physiological behavior and development of maize plants under hydric deficit inoculated with the AMF Rhizophagus clarus and Claroideoglomus etunicatum and the commercial inoculant ROOTELLA BR in nonsterilized soil as a strategy to mitigate the effects of drought in the crop. Corn seeds were grown and inoculated with R. clarus, C. etunicatum and the commercial inoculant ROOTELLA BR separately at sowing. The plants were grown in a greenhouse and submitted to water deficit in stage V3, keeping the pots at 20% field capacity for 10 days. The first analyses were performed, followed by reirrigation for 2 days, and the analyses were performed again. The experiment was a double factorial, with 2 water treatments (irrigated and water deficit) × 4 inoculation treatments (control, ROOTELLA BR, R. clarus, C. etunicatum) × 5 replicates per treatment, totaling 40 vessels. The results indicate that the plants were able to recover favorably according to the physiological data presented. It is noted that in inoculated plants, there was no damage to the photosynthetic apparatus. These data demonstrate that AMF contribute greatly to better plant recovery after a dry period and a new irrigation period. Inoculation with AMF favors postwater stress recovery in plants.

Abstract Phenolic compounds are natural dyes contained in sugarcane juice and represent an important parameter in industrial processing, as they significantly affect the color formation of raw sugar. This study investigated the relationship between color formation and phenolic compounds during a Very High Polarization (VHP) sugar manufacturing process, in which the RB92579 genotype represents about 50% of the processed sugarcane. The products evaluated during the industrial processing of sugarcane were: raw juice, mixed juice, lime-treated juice, clarified juice, syrup, massecuite, and VHP sugar. The polyphenols catechin (CAT), chlorogenic acid (CGA), caffeic acid (CAF), vanillin (VAN), syringaldehyde (SYR), p-coumaric acid (p-COU), coumarin (CUM), and rutin (RUT) were quantified by high-performance liquid chromatography (HPLC). The highest concentrations of CGA and SYR were obtained from the sucrose crystallization product (massecuite), similarly to the parameters of color, total phenols and the total polyphenol content. CGA was the predominant polyphenol in the samples of clarified juice, syrup, massecuite and VHP sugar, with the latter presenting concentrations above 50%. The presence of phenolic compounds provided different indices of color during the production process. In this context, chlorogenic acid (CGA) was the compound that presented the most expressive results, contributing significantly to the formation of color in sugarcane processing products, which is a fact that has not yet been reported in the literature. The color of the VHP sugar crystals also had a positive relationship with the concentration of phenolics, with greater evidence for CGA.

Abstract Tremors are common disorders characterized by an involuntary and relatively rhythmic oscillation that can occur in any part of the body and may be physiological or associated with some pathological condition. It is known that the mass loading can change the power spectral distribution of the tremor. Nowadays, many instruments have been used in the evaluation of tremors with bult-in inertial sensors, such as smartphones and wearables, which can significantly differ in the device mass. The aim of this study was to compare the quantification of hand tremor using Fourier spectral techniques obtained from readings of accelerometers built-in a lightweight handheld device and a commercial smartphone in healthy young subjects. We recruited 28 healthy right-handed subjects with ages ranging from 18 to 40 years. We tested hand tremors at rest and postural conditions using lightweight wearable device (5.7 g) and smartphone (169 g). Comparing both devices at resting tremor, we found with smartphone the power distribution of peak ranging 5 and 12 Hz in both hands. With wearable, the result was similar but less evident. When comparing both devices in postural tremor, there were significant differences in both frequency ranges in peak frequency and peak amplitude in both hands. Our main findings show that in resting condition the hand tremor spectrum had a higher peak amplitude in the 5–12 Hz range when the tremor was recorded with smartphones, and in postural condition there was a significantly (p

Abstract Bipolar disorder (BD) is associated with systemic toxicity, represented by changes in biomarkers associated with mood episodes, leading to neurological damage, which may reflect cognitive functions and functionality and the progression of the disease. We aimed to analyze the effect of four biomarkers, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and thiobarbituric acid reactive substances (TBA-RS), related to oxidative stress in BD and to correlate them with cognitive functions and functionality. We studied 50 bipolar types I/II patients in the euthymic phase, which was divided into two subgroups with 25 patients each (≤ 3 years and ≥ 10 years of diagnosis, from the first episode of mania) and 25 control patients. To analyze frontal cognitive functions and functionality, we used the Frontal Assessment Battery (FAB) and Functioning Assessment Short Test (FAST) tests, respectively. The scores of the FAST and FAB tests showed an increase and decrease respectively, in both bipolar groups, when compared to the control group, demonstrating impairment in cognitive functions and functionality since the disease onset. In addition, changes occurred in all six domains of the FAST test, and in four domains of the FAB test in bipolar patients when compared to the control group. Regarding oxidative stress biomarkers, we did not find changes in SOD and GSH-Px activities; however, a significant increase in CAT activity and lipid peroxidation was observed in both groups, although the patients were euthymic and medicated. These results allow us to raise the hypothesis that since the beginning of the disease, the euthymic bipolar patient has presented a level of oxidative stress, which gets worse with the evolution of the disease, promoting impairments in the frontal cognitive functions and functionality gradually.

Abstract In the present study, we aimed to evaluate the therapeutic effect of Passiflora edulis fruit peel aqueous (AFA) extract as an adjuvant to insulin to confer nephroprotection against streptozotocin-induced diabetes. Male Wistar rats were divided into four groups based on treatment received for 60 days: diabetic (DB), control (CTL), insulin (INS), and insulin + AFA extract (INS + AFA). mRNA and protein expression levels of podocyte (nephrin, podocin, and WT1) and tubular (megalin) proteins were measured in kidney tissue specimens and urine. Biochemical parameters and kidney histopathology were also examined. Herein, the INS + AFA group showed superior glycemic control, which resulted in the reduction of urinary albumin/creatinine ratio, maintenance of baseline levels of Nphs1, Nphs2, Wt1, and Lrp2 mRNA expression, prevention of protein loss from the kidney tissue into the urinary space, along with the maintenance of glomerular basement membrane thickness, hyalinization, glomerular and tubulointerstitial fibrosis at values approximating those of the CTL group and significantly lower than those in the DB group. Therefore, these results suggest that, as an anti-diabetic agent, the AFA extract adjuvant to insulin could reduce and potentially prevent diabetic kidney disease.

Abstract Coronavirus disease 2019 (COVID-19) continues to significantly impact the global population, thus countermeasure platforms that enable rapid development of therapeutics against variants of SARS-CoV-2 are essential. We report use of a phage display human antibody library approach to rapidly identify neutralizing antibodies (nAbs) against SARS-CoV-2. We demonstrate the binding and neutralization capability of two nAbs, STI-2020 and STI-5041, against the SARS-CoV-2 WA-1 strain as well as the Alpha and Beta variants. STI-2020 and STI-5041 were protective when administered intravenously or intranasally in the golden (Syrian) hamster model of COVID-19 challenged with the WA-1 strain or Beta variant. The ability to administer nAbs intravenously and intranasally may have important therapeutic implications and Phase 1 healthy subjects clinical trials are ongoing.

Food security remains a principal challenge in the developing tropics where communities rely heavily on marine-based protein. While some improvements in fisheries management have been made in these regions, a large fraction of coastal fisheries remain unmanaged, mismanaged, or use only crude input controls. These quasi-open-access conditions often lead to severe overfishing, depleted stocks, and compromised food security. A possible fishery management approach in these institution-poor settings is to implement fully protected marine protected areas (MPAs). Although the primary push for MPAs has been to solve the conservation problems that arise from mismanagement, MPAs can also benefit fisheries beyond their borders. The literature has not completely characterized how to design MPAs under diverse ecological and economic conditions when food security is the objective. We integrated four key biological and economic variables (i.e., fish population growth rate, fish mobility, fish price, and fishing cost) as well as an important aspect of reserve design (MPA size) into a general model and determined their combined influence on food security when MPAs are implemented in an open-access setting. We explicitly modeled open-access conditions that account for the behavioral response of fishers to the MPA; this approach is distinct from much of the literature that focuses on assumptions of scorched earth (i.e., severe over-fishing), optimized management, or an arbitrarily defined fishing mortality outside the MPAs boundaries. We found that the MPA size that optimizes catch depends strongly on economic variables. Large MPAs optimize catch for species heavily harvested for their high value and/or low harvesting cost, while small MPAs or no closure are best for species lightly harvested for their low value and high harvesting cost. Contrary to previous theoretical expectations, both high and low mobility species are expected to experience conservation benefits from protection, although, as shown previously, greater conservation benefits are expected for low mobility species. Food security benefits from MPAs can be obtained from species of any mobility. Results deliver both qualitative insights and quantitative guidance for designing MPAs for food security in open-access fisheries.

Abstract Depression is a common mental disorder that may comprise distinct, underlying symptom patterns over time. Associations between stressful life events throughout the civilian lifecourse—including during childhood—and adult depression have been documented in many populations, but are less commonly assessed in military samples. We identified different trajectories of depression symptoms across four years in a military cohort using latent class growth analysis, and investigated the relationship between these trajectories and two domains of civilian life experiences: childhood adversity (e.g., being mistreated during childhood) and more proximal stressful experiences (e.g., divorce). A four-group depression model was identified, including a symptom-free group (62%), an increasing symptom group (13%), a decreasing symptom group (16%), and a “chronic” symptom group (9%). Compared to the symptom-free group, soldiers with childhood adversity were more likely to be in the chronic depression, decreasing, and increasing symptom groups. Time-varying adult stressors had the largest effect on depression symptoms for the increasing symptom group compared to other groups, particularly in the last two years of follow-up. This study indicates the importance of considering events from throughout the lifecourse—not only those from deployment—when studying the mental health of servicemembers.

Abstract Soybean (Glycine max L.) is an economically important crop, and is cultivated worldwide, although increasingly long periods of drought have reduced the productivity of this plant. Research has shown that inoculation with arbuscular mycorrhizal fungi (AMF) provides a potential alternative strategy for the mitigation of drought stress. In the present study, we measured the physiological and morphological performance of two soybean cultivars in symbiosis with Rhizophagus clarus that were subjected to drought stress (DS). The soybean cultivars Anta82 and Desafio were grown in pots inoculated with R. clarus. Drought stress was imposed at the V3 development stage and maintained for 7 days. A control group, with well-irrigated plants and no AMF, was established simultaneously in the greenhouse. The mycorrhizal colonization rate, and the physiological, morphological, and nutritional traits of the plants were recorded at days 3 and 7 after drought stress conditions were implemented. The Anta82 cultivar presented the highest percentage of AMF colonization, and N and K in the leaves, whereas the DS group of the Desafio cultivar had the highest water potential and water use efficiency, and the DS + AMF group had thermal dissipation that permitted higher values of Fv/Fm, A, and plant height. The results of the principal components analysis demonstrated that both cultivars inoculated with AMF performed similarly under DS to the well-watered plants. These findings indicate that AMF permitted the plant to reduce the impairment of growth and physiological traits caused by drought conditions.

Abstract Fungal infections represent a major global health problem affecting over a billion people that kills more than 1.5 million annually. In this study, we employed an integrative approach to reveal the landscape of the human immune responses to Candida spp. through meta-analysis of microarray, bulk, and single-cell RNA sequencing (scRNA-seq) data for the blood transcriptome. We identified across these different studies a consistent interconnected network interplay of signaling molecules involved in both Toll-like receptor (TLR) and interferon (IFN) signaling cascades that is activated in response to different Candida species (C. albicans, C. auris, C. glabrata, C. parapsilosis, and C. tropicalis). Among these molecules are several types I IFN, indicating an overlap with antiviral immune responses. scRNA-seq data confirmed that genes commonly identified by the three transcriptomic methods show cell type-specific expression patterns in various innate and adaptive immune cells. These findings shed new light on the anti-Candida immune response, providing putative molecular pathways for therapeutic intervention.