A Macrophage Colony-Stimulating-Factor-Producing γδ T Cell Subset Prevents Malarial Parasitemic Recurrence.

Despite evidence that γδ T cells play an important role during malaria, their precise role remains unclear. During murine malaria induced by Plasmodium chabaudi infection and in human P. falciparum infection, we found that γδ T cells expanded rapidly after resolution of acute parasitemia, in contrast to αß T cells that expanded at the acute stage and then declined. Single-cell sequencing showed that TRAV15N-1 (Vδ6.3) γδ T cells were clonally expanded in mice and had convergent complementarity-determining region 3 sequences. These γδ T cells expressed specific cytokines, M-CSF, CCL5, CCL3, which are known to act on myeloid cells, indicating that this γδ T cell subset might have distinct functions. Both γδ T cells and M-CSF were necessary for preventing parasitemic recurrence. These findings point to an M-CSF-producing γδ T cell subset that fulfills a specialized protective role in the later stage of malaria infection when αß T cells have declined.

The Aedes aegypti peritrophic matrix controls arbovirus vector competence through HPx1, a heme-induced peroxidase.

Aedes aegypti mosquitoes are the main vectors of arboviruses. The peritrophic matrix (PM) is an extracellular layer that surrounds the blood bolus. It acts as an immune barrier that prevents direct contact of bacteria with midgut epithelial cells during blood digestion. Here, we describe a heme-dependent peroxidase, hereafter referred to as heme peroxidase 1 (HPx1). HPx1 promotes PM assembly and antioxidant ability, modulating vector competence. Mechanistically, the heme presence in a blood meal induces HPx1 transcriptional activation mediated by the E75 transcription factor. HPx1 knockdown increases midgut reactive oxygen species (ROS) production by the DUOX NADPH oxidase. Elevated ROS levels reduce microbiota growth while enhancing epithelial mitosis, a response to tissue damage. However, simultaneous HPx1 and DUOX silencing was not able to rescue bacterial population growth, as explained by increased expression of antimicrobial peptides (AMPs), which occurred only after double knockdown. This result revealed hierarchical activation of ROS and AMPs to control microbiota. HPx1 knockdown produced a 100-fold decrease in Zika and dengue 2 midgut infection, demonstrating the essential role of the mosquito PM in the modulation of arbovirus vector competence. Our data show that the PM connects blood digestion to midgut immunological sensing of the microbiota and viral infections.

Recurrent droughts increase risk of cascading tipping events by outpacing adaptive capacities in the Amazon rainforest.

Tipping elements are nonlinear subsystems of the Earth system that have the potential to abruptly shift to another state if environmental change occurs close to a critical threshold with large consequences for human societies and ecosystems. Among these tipping elements may be the Amazon rainforest, which has been undergoing intensive anthropogenic activities and increasingly frequent droughts. Here, we assess how extreme deviations from climatological rainfall regimes may cause local forest collapse that cascades through the coupled forest-climate system. We develop a conceptual dynamic network model to isolate and uncover the role of atmospheric moisture recycling in such tipping cascades. We account for heterogeneity in critical thresholds of the forest caused by adaptation to local climatic conditions. Our results reveal that, despite this adaptation, a future climate characterized by permanent drought conditions could trigger a transition to an open canopy state particularly in the southern Amazon. The loss of atmospheric moisture recycling contributes to one-third of the tipping events. Thus, by exceeding local thresholds in forest adaptive capacity, local climate change impacts may propagate to other regions of the Amazon basin, causing a risk of forest shifts even in regions where critical thresholds have not been crossed locally.

Quantum Definition of Molecular Structure.

Molecular structure, a key concept of chemistry, has remained elusive from the perspective of all-particle quantum mechanics, despite many efforts. Viewing molecular structure as a manifestation of strong statistical correlation between nuclear positions, we propose a practical method based on Markov chain Monte Carlo sampling and unsupervised machine learning. Application to the D3+ molecule unambiguously shows that it possesses an equilateral triangular structure. These results provide a major step forward in our understanding of the molecular structure from fundamental quantum principles.

Automatic Smoke Analysis in Minimally Invasive Surgery by Image-Based Machine Learning.

INTRODUCTION: Minimally Invasive Surgery uses electrosurgical tools that generate smoke. This smoke reduces the visibility of the surgical site and spreads harmful substances with potential hazards for the surgical staff. Automatic image analysis may provide assistance. However, the existing studies are restricted to simple clear versus smoky image classification. MATERIALS AND METHODS: We propose a novel approach using surgical image analysis with machine learning, including deep neural networks. We address three tasks: 1) smoke quantification, which estimates the visual level of smoke, 2) smoke evacuation confidence, which estimates the level of confidence to evacuate smoke, and 3) smoke evacuation recommendation, which estimates the evacuation decision. We collected three datasets with expert annotations. We trained end-to-end neural networks for the three tasks. We also created indirect predictors using task 1 followed by linear regression to solve task 2 and using task 2 followed by binary classification to solve task 3. RESULTS: We observe a reasonable inter-expert variability for tasks 1 and a large one for tasks 2 and 3. For task 1, the expert error is 17.61 percentage points (pp) and the neural network error is 18.45 pp. For tasks 2, the best results are obtained from the indirect predictor based on task 1. For this task, the expert error is 27.35 pp and the predictor error is 23.60 pp. For task 3, the expert accuracy is 76.78% and the predictor accuracy is 81.30%. CONCLUSIONS: Smoke quantification, evacuation confidence, and evaluation recommendation can be achieved by automatic surgical image analysis with similar or better accuracy as the experts.

Fish oil supplementation during pregnancy decreases liver endocannabinoid system and lipogenic markers in newborn rats exposed to maternal high-fat diet.

PURPOSE: Maternal high-fat diet (HF) programs obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), hypertriglyceridemia, and hyperglycemia associated with increased endocannabinoid system (ECS) in the liver of adult male rat offspring. We hypothesized that maternal HF would induce sex specific ECS changes in the liver of newborn rats, prior to obesity onset, and maternal fish oil (FO) supplementation would reprogram the ECS and lipid metabolism markers preventing liver triglycerides (TG) accumulation. METHODS: Female rats received a control (CT) (10.9% fat) or HF (28.7% fat) diet 8 weeks prior to mating and during pregnancy. A subgroup of HF dams received 3% FO supplementation in the HF diet (35.4% fat) during pregnancy (HFFO). Serum hormones and liver TG, ECS, lipid metabolism, oxidative stress and autophagy markers were assessed in male and female newborn offspring. RESULTS: Maternal HF diet increased liver cannabinoid receptor 1 (CB1) in males and decreased CB2 in females, with no effect on liver TG. Maternal FO supplementation reduced liver CB1 regardless of the offspring sex, but reduced TG liver content only in females. FO reduced the liver content of the endocannabinoid anandamide in males, and the content of 2-arachidonoylglycerol in both sexes. Maternal HF increased lipogenic and decreased lipid oxidation markers, and FO induced the opposite regulation in the liver of offspring. CONCLUSION: Prenatal HF and FO differentially modulate liver ECS in the offspring before obesity and MASLD development. These results suggest that maternal nutrition at critical stages of development can modulate the offspring's ECS, predisposing or preventing the onset of metabolic diseases.

Factors associated with mortality of patients with COVID-19 on invasive mechanical ventilation: A retrospective cohort study in a university hospital in Northeastern Brazil.

The aim of this study is to identify the factors associated with mortality in patients with COVID-19 undergoing invasive mechanical ventilation at a university hospital in Northeastern Brazil. This is a retrospective cohort from April to August 2020 through an analysis of medical records, considering the demographic profile, comorbidities, complications, supports, respiratory and laboratory parameters. A total of 65 patients required invasive mechanical ventilation, of which 64.6% died in the ICU. They were older, had more comorbidities, shorter length of stay in the intensive care unit, received more support such as palliative care and two vasopressors simultaneously, showed lower levels of pH, hemoglobin and calcium, and higher levels of bicarbonate, lactate, prothrombin time, international normalized ratio, troponin and ferritin at the start of invasive mechanical ventilation. Furthermore, the time course of pH, arterial oxygen partial pressure to fractional inspired oxygen ratio, arterial carbon dioxide partial pressure, lactate, hemoglobin, platelets, lymphocytes, neutrophil-to-lymphocyte ratio, coagulation parameters, calcium, urea, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, ferritin, static compliance, airway resistance, tidal volume, and noradrenaline doses showed association with mortality. There was a high mortality rate in invasively mechanically ventilated COVID-19 patients, with some associated factors identified at the start of invasive mechanical ventilation and others identified over time.

Correction: Oliveira et al. Effect of Polymer Hydrophobicity in the Performance of Hybrid Gel Gas Sensors for E-Noses. Sensors 2023, 23, 3531.

In the published publication [...].

Atrial Fibrillation in Endurance Training Athletes: Scoping Review.

Background: Moderate regular physical activity is indicated to avoid atrial fibrillation (AF), whereas athletes should be counseled that long-lasting vigorous sports engagement may cause AF, according to the 2016 European Society of Cardiology (ESC) recommendations for AF treatment. Exercise and AF are complex. Objectives: To evaluate the relationship between Endurance training and AF, in addition to the starting point/trigger by which Endurance Training causes impairment of cardiac function and AF, considering the time and intensity of Endurance training. Materials and Methods: We synthesized evidence from articles published in the PubMed, EMBASE, and SciELO databases using their respective Boolean operators. A total of 112 original articles related to AF and endurance athletes published up to the year 2023 were reviewed. Results: Our study verified multiples aspects of the genesis of AF in athletes, such as cardiac adaptations to exercise, disturbances in cardiac injury biomarkers, sex differences in cardiac adaptations and their role in AF risk, and the relationship between body composition (height, weight, and physical fitness) and AF pathogenesis. Conclusions: Variations in cardiac structure (increased atrial thickness and size in addition to myocardial fibrosis) and significant increases in vagal tone (sinus bradycardia and imbalances in sympathetic and parasympathetic activation) shorten the refractory period shortening in athletes, induce the onset of re-entrance mechanisms, and serve as ectopic triggers that can lead to AF.

Similarities and controversies in imaging of pediatric renal tumors: A SIOP-RTSG and COG collaboration.

Malignant renal tumors are rare in children, and Wilms tumors (WTs) are the most common subtype. Imaging plays an essential role in the diagnosis, staging, and follow-up of these patients. Initial workup for staging is mainly performed by cross-sectional imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Imaging approach within the two core international groups, the Children's Oncology Group (COG, North America) and the International Society of Pediatric Oncology - Renal Tumor Study Group (SIOP-RTSG, Europe), differs. Whereas abdominal ultrasound (US) is used for the initial diagnosis of a suspected pediatric renal tumor globally, COG protocols support the use of CT or MRI for locoregional staging, contrary to the preference for MRI over CT for abdominopelvic evaluation within the SIOP-RTSG. The purpose of this manuscript is to summarize current imaging approaches, highlighting differences and similarities within these core international groups, while focusing on future innovative efforts and collaboration within the HARMONICA initiative.

SANS Spectra with PLUMED: Implementation and Application to Metainference.

Using small-angle scattering with either X-ray or neutron sources has become common in the investigation of soft-matter systems. These experiments provide information about the coarse shape of the scattered objects, but obtaining more-detailed information can usually only be achieved with the aid of molecular simulations. In this Application Note, we report the implementation of an extension in PLUMED to compute the small-angle neutron scattering (SANS), which can be used for data processing as well for enhanced sampling, in particular with the metainference method to bias simulations and sample structures with a resulting spectrum in agreement with an experimental reference. Our implementation includes a resolution function that can be used to smear the SANS intensities according to beamline error sources and is compatible with both all-atom and coarse-grained simulations. Scripts to aid in the calculation of the scattering lengths when the system is coarse-grained and to aid in preparing the inputs are provided. We illustrate the use of the implementation with metainference by performing coarse-grained simulations of beta-octylglucoside and dodecylphosphocholine micelles in water. With different software and different Hamiltonians, we show that the metainference SANS bias can drive micelles to be split and to change shapes to achieve a better agreement with the experimental reference.

On screen experiment showed that becoming a parent for the first time shifted people's priorities from themselves to their infant at 1 year of age.

AIM: This study used a screen-based perceptual matching task to see how non-parents, people trying to get pregnant, and those who had given birth prioritised shapes and labels relating to self or infant conditions. METHODS: The study took place at Aarhus University Hospital in Denmark from December 2016 to November 2021. Recruitment methods included family planning clinics, social media, online recruitment systems and local bulletin boards. The modified perceptual matching task linked five shapes to five labels, including self and infant. RESULTS: We found that 67 males and females with a mean age of 24.4 ± 3 years, who had no plans to become parents in the near future, reacted faster and more accurately to self-shapes and labels (p < 0.001), which validated the experiment. The 56 participants aged 27.1 ± 4.4 years who were actively trying to become parents showed no statistically significant prioritisation. A subset of 21 participants aged 28.7 ± 4.4 years showed faster response times to infant than self-shapes and labels 1 year after giving birth (p < 0.001). CONCLUSION: Healthy first-time parents showed faster reactions to infant than self-conditions 1 year after giving birth, in contrast to the other two groups.

Air velocity spatial variability in open Compost-Bedded Pack Barn system with positive pressure ventilation.

In Compost-Bedded Pack Barn (CBP) systems, air velocity is linked with the thermal comfort of housed dairy cattle and bedding quality and, therefore, assessing ventilation efficiency is essential. In this context, the objective of this study was to evaluate and characterize dependence and spatial distribution of air velocity at the 1.5 m height (vair,M) and at bedding level (vair,B) in an open CBP system with positive pressure ventilation. The study was conducted in 2021, in a facility located in the Zona da Mata region, Minas Gerais, Brazil. The facility area was divided into a mesh composed of 55 equidistant points, where vair,M and vair,B data were collected in the morning (09:00 a.m.) and afternoon (03:00 p.m.) periods, during three weeks in Brazilian winter. Geostatistics techniques were used to assess dependence and spatial distribution. In both periods evaluated, there were a strong occurrence of spatial dependence and non-uniform vair,M and vair,B distributions. The vair,M and vair,B values were lower than recommended (1.8 m∙s-1) in more than 65.0% of the area. Adequate ventilation levels were observed only in the first 20.0 m of the facility, from Southeast to Northwest, because of the fan lines present.

Identification of phlebotomine sand fly (Diptera: Psychodidae) in Atlantic forest fragments and their dispersal to urban area.

The geographical distribution of sand flies in Brazil has been the subject of some studies, yet there is no information about the phlebotomine fauna in João Pessoa, State of Paraíba, Brazil. The aim of this work is to evaluate the occurrence and distribution of sand flies in the Atlantic forest fragments and to evaluate a possible dispersion in 06 nearby districts. Light traps were used during three consecutive nights, supplemented by an aspirator during the dry period and rainy season. A total of 222 sand flies were found, 143 (130 males and 13 females) in the Atlantic forest, and 79 in urban areas. During the entire dry season, three species of phlebotomine sand flies were recorded in 11 forest fragments, Lutzomyia longipalpis, Lu. migonei and Lu. whitmani. During the rainy season, only Lu. longipalpis was found. This was the only species identified in the studied neighborhoods during both seasons. The differences in diversity of sand flies encountered between natural habitats and urban areas may thus be correlated mostly with adaptations to particular habitats and availability of food. One species (Lu. longipalpis) appears to be rapidly adapting to urban areas because of deforestation.

Ocular lesions in cats diagnosed with systemic sporotrichosis.

OBJECTIVES: To describe the most common ocular lesions and demonstrate the frequency of ophthalmic involvement in a group of cats with systemic sporotrichosis. ANIMALS STUDIED: Two hundred seventy-four cats diagnosed with systemic sporotrichosis. The inclusion criteria included previous positive cytopathological examination, histopathological examination, or fungal culture. PROCEDURES: In a prospective case-control study, 274 cats diagnosed with systemic sporotrichosis underwent ophthalmic evaluation and received treatment for systemic sporotrichosis. Of these animals, 63 had ocular abnormalities which were recorded, and conjunctivitis was scored from 0 to 5. Diagnostic techniques utilized included fungal culture, as well as cytopathological (10 eyes; 10 cats), and histopathological examination of the palpebral conjunctiva and eyes (2 eyes). RESULTS: Cytopathological and histopathological examination of the conjunctiva, as well as fungal culture, proved to be important tests for the detection of Sporothrix sp. Five cats without the evidence of ophthalmic abnormalities also had a positive fungal culture. The identified ocular lesions in animals with systemic sporotrichosis included increased serous discharge (79 eyes; 53 cats), blepharoconjunctivitis (33 eyes; 25 cats), conjunctivitis (39 eyes, 20 cats), blepharitis (9 eyes; 8 cats), uveitis (5 eyes; 3 cats), and Florida keratopathy-like lesions (2 eyes; 1 cat). CONCLUSION: Sporotrichosis should be considered a differential diagnosis for conjunctivitis and blepharoconjunctivitis, especially in endemic areas. Fungal culture and cytopathology of ocular discharge and histopathological examinations of the conjunctiva are important for the diagnosis of ophthalmic sporotrichosis, although not all cats underwent laboratory testing in this study. Ocular discharge could be a source of contagion transmission.

Effect of Polymer Hydrophobicity in the Performance of Hybrid Gel Gas Sensors for E-Noses.

Relative humidity (RH) is a common interferent in chemical gas sensors, influencing their baselines and sensitivity, which can limit the performance of e-nose systems. Tuning the composition of the sensing materials is a possible strategy to control the impact of RH in gas sensors. Hybrid gel materials used as gas sensors contain self-assembled droplets of ionic liquid and liquid crystal molecules encapsulated in a polymeric matrix. In this work, we assessed the effect of the matrix hydrophobic properties in the performance of hybrid gel materials for VOC sensing in humid conditions (50% RH). We used two different polymers, the hydrophobic PDMS and the hydrophilic bovine gelatin, as polymeric matrices in hybrid gel materials containing imidazolium-based ionic liquids, [BMIM][Cl] and [BMIM][DCA], and the thermotropic liquid crystal 5CB. Better accuracy of VOC prediction is obtained for the hybrid gels composed of a PDMS matrix combined with the [BMIM][Cl] ionic liquid, and the use of this hydrophobic matrix reduces the effect of humidity on the sensing performance when compared to the gelatin counterpart. VOCs interact with all the moieties of the hybrid gel multicomponent system; thus, VOC correct classification depends not only on the polymeric matrix used, but also on the IL selected, which seems to be key to achieve VOCs discrimination at 50% RH. Thus, hybrid gels' tunable formulation offers the potential for designing complementary sensors for e-nose systems operable under different RH conditions.

A multiple criteria approach for building a pandemic impact assessment composite indicator: The case of COVID-19 in Portugal.

The COVID-19 pandemic has caused major damage and disruption to social, economic, and health systems (among others). In addition, it has posed unprecedented challenges to public health and policy/decision-makers who have been responsible for designing and implementing measures to mitigate its strong negative impact. The Portuguese health authorities have used decision analysis techniques to assess the impact of the pandemic and implemented measures for counties, regions, or across the entire country. These decision tools have been subject to some criticism and many stakeholders requested novel approaches. In particular, those which considered the dynamic changes in the pandemic's behaviour due to new virus variants and vaccines. A multidisciplinary team formed by researchers from the COVID-19 Committee of Instituto Superior Técnico at the University of Lisbon (CCIST analyst team) and physicians from the Crisis Office of the Portuguese Medical Association (GCOM expert team) collaborated to create a new tool to help politicians and decision-makers to fight the pandemic. This paper presents the main steps that led to the building of a pandemic impact assessment composite indicator applied to the specific case of COVID-19 in Portugal. A multiple criteria approach based on an additive multi-attribute value theory aggregation model was used to build the pandemic assessment composite indicator. The parameters of the additive model were devised based on an interactive socio-technical and co-constructive process between the CCIST and GCOM team members. The deck of cards method was the adopted technical tool to assist in the assessment the value functions as well as in the assessment of the criteria weights. The final tool was presented at a press conference and had a powerful impact on the Portuguese media and on the main health decision-making stakeholders in the country. In this paper, a completed mathematical and graphical description of this tool is presented.

Calculating herbage utilization and intake by dairy cows under subtropical conditions using conventional field measurement techniques or the HerbValo method.

This study aimed to evaluate the HerbValo method in comparison to conventional field measurement techniques as a tool for estimating the herbage utilization and dry matter (DM) intake by grazing dairy cows under subtropical conditions. It was carried out during 18 months in a commercial farm of Southern Brazil. The herbage utilization was estimated monthly in two to four randomly selected paddocks (total n = 40) using the rising-plate meter or the double-sampling technique. In parallel, the herbage utilization was estimated by the HerbValo method, which is based on simple descriptions of the herd, supplements, pasture and grazing management. Values of herbage utilization estimated by field techniques were linearly (P < 0.01) related to those estimated by HerbValo, with no effect of pasture type (tropical vs. temperate) on the origin or on the slope of the regression (slope = 0.97; origin = -0.1; R2 = 0.81; rsd = 0.17 t DM/ha). At cow × day level, values of herbage intake estimated by field techniques were also linearly related to those estimated by HerbValo (P < 0.01; R2 = 0.82; rsd = 1.30 kg DM/cow/day). A negative linear relationship (P < 0.01) between herbage and supplement intake was obtained for both field (slope = -1.06; R2 = 0.72; rsd = 1.64) and HerbValo (slope = -0.92; R2 = 0.82; rsd = 1.08) approaches. Herbage utilization and intake by a dairy herd in a subtropical grazing-based system can be reliably estimated by the HerbValo method with the advantage of not requiring direct field pasture measurements.

Directional turnover towards larger-ranged plants over time and across habitats.

Species turnover is ubiquitous. However, it remains unknown whether certain types of species are consistently gained or lost across different habitats. Here, we analysed the trajectories of 1827 plant species over time intervals of up to 78 years at 141 sites across mountain summits, forests, and lowland grasslands in Europe. We found, albeit with relatively small effect sizes, displacements of smaller- by larger-ranged species across habitats. Communities shifted in parallel towards more nutrient-demanding species, with species from nutrient-rich habitats having larger ranges. Because these species are typically strong competitors, declines of smaller-ranged species could reflect not only abiotic drivers of global change, but also biotic pressure from increased competition. The ubiquitous component of turnover based on species range size we found here may partially reconcile findings of no net loss in local diversity with global species loss, and link community-scale turnover to macroecological processes such as biotic homogenisation.

Centromere protein J is overexpressed in human glioblastoma and promotes cell proliferation and migration.

Glioblastoma is the most common and malignant type of primary brain tumor. Previous studies have shown that alterations in centrosome amplification and its components are frequently found in treatment-resistant tumors and may be associated with tumor progression. A centrosome protein essential for centrosome biogenesis is the centromere protein J (CENPJ), known to control the proliferation of neural progenitors and hepatocarcinoma cells, and also neuronal migration. However, it remains unknown the role of CENPJ in glioblastoma. Here we show that CENPJ is overexpressed in human glioblastoma cell lines in comparison to human astrocytes. Using bioinformatics analysis, we find that high Cenpj expression is associated with poor prognosis in glioma patients. Examining Cenpj loss of function in glioblastoma by siRNA transfection, we find impairments in cell proliferation and migration. Using a Cenpj mutant version with the deleted PN2-3 or TCP domain, we found that a conserved PN2-3 region is required for glioblastoma migration. Moreover, Cenpj downregulation modulates glioblastoma morphology resulting in microtubules stabilization and actin filaments depolymerization. Altogether, our findings indicate that CENPJ controls relevant aspects of glioblastoma progression and might be a target for therapeutic intervention and a biomarker for glioma malignancy.