The disulfide catalyst QSOX1 maintains the colon mucosal barrier by regulating Golgi glycosyltransferases.

Mucus is made of enormous mucin glycoproteins that polymerize by disulfide crosslinking in the Golgi apparatus. QSOX1 is a catalyst of disulfide bond formation localized to the Golgi. Both QSOX1 and mucins are highly expressed in goblet cells of mucosal tissues, leading to the hypothesis that QSOX1 catalyzes disulfide-mediated mucin polymerization. We found that knockout mice lacking QSOX1 had impaired mucus barrier function due to production of defective mucus. However, an investigation on the molecular level revealed normal disulfide-mediated polymerization of mucins and related glycoproteins. Instead, we detected a drastic decrease in sialic acid in the gut mucus glycome of the QSOX1 knockout mice, leading to the discovery that QSOX1 forms regulatory disulfides in Golgi glycosyltransferases. Sialylation defects in the colon are known to cause colitis in humans. Here we show that QSOX1 redox control of sialylation is essential for maintaining mucosal function.

An allosteric redox switch involved in oxygen protection in a CO2 reductase.

Metal-dependent formate dehydrogenases reduce CO2 with high efficiency and selectivity, but are usually very oxygen sensitive. An exception is Desulfovibrio vulgaris W/Sec-FdhAB, which can be handled aerobically, but the basis for this oxygen tolerance was unknown. Here we show that FdhAB activity is controlled by a redox switch based on an allosteric disulfide bond. When this bond is closed, the enzyme is in an oxygen-tolerant resting state presenting almost no catalytic activity and very low formate affinity. Opening this bond triggers large conformational changes that propagate to the active site, resulting in high activity and high formate affinity, but also higher oxygen sensitivity. We present the structure of activated FdhAB and show that activity loss is associated with partial loss of the metal sulfido ligand. The redox switch mechanism is reversible in vivo and prevents enzyme reduction by physiological formate levels, conferring a fitness advantage during O2 exposure.

Asymmetric dimerization in a transcription factor superfamily is promoted by allosteric interactions with DNA.

Transcription factors, such as nuclear receptors achieve precise transcriptional regulation by means of a tight and reciprocal communication with DNA, where cooperativity gained by receptor dimerization is added to binding site sequence specificity to expand the range of DNA target gene sequences. To unravel the evolutionary steps in the emergence of DNA selection by steroid receptors (SRs) from monomeric to dimeric palindromic binding sites, we carried out crystallographic, biophysical and phylogenetic studies, focusing on the estrogen-related receptors (ERRs, NR3B) that represent closest relatives of SRs. Our results, showing the structure of the ERR DNA-binding domain bound to a palindromic response element (RE), unveil the molecular mechanisms of ERR dimerization which are imprinted in the protein itself with DNA acting as an allosteric driver by allowing the formation of a novel extended asymmetric dimerization region (KR-box). Phylogenetic analyses suggest that this dimerization asymmetry is an ancestral feature necessary for establishing a strong overall dimerization interface, which was progressively modified in other SRs in the course of evolution.

Opinion dynamics in financial markets via random networks.

We investigate financial market dynamics by introducing a heterogeneous agent-based opinion formation model. In this work, we organize individuals in a financial market according to their trading strategy, namely, whether they are noise traders or fundamentalists. The opinion of a local majority compels the market exchanging behavior of noise traders, whereas the global behavior of the market influences the decisions of fundamentalist agents. We introduce a noise parameter, q, to represent the level of anxiety and perceived uncertainty regarding market behavior, enabling the possibility of adrift financial action. We place individuals as nodes in an Erdös-Rényi random graph, where the links represent their social interactions. At any given time, individuals assume one of two possible opinion states ±1 regarding buying or selling an asset. The model exhibits fundamental qualitative and quantitative real-world market features such as the distribution of logarithmic returns with fat tails, clustered volatility, and the long-term correlation of returns. We use Student's t distributions to fit the histograms of logarithmic returns, showing a gradual shift from a leptokurtic to a mesokurtic regime depending on the fraction of fundamentalist agents. Furthermore, we compare our results with those concerning the distribution of the logarithmic returns of several real-world financial indices.

Enhanced Electrochemiluminescence at the Gas/Liquid Interface of Bubbles Propelled into Solution.

Electrochemiluminescence (ECL) is typically confined to a micrometric region from the electrode surface. This study demonstrates that ECL emission can extend up to several millimeters away from the electrode employing electrogenerated chlorine bubbles. The mechanism behind this bubble-enhanced ECL was investigated using an Au microelectrode in chloride-containing and chloride-free electrolyte solutions. We discovered that ECL emission at the gas/solution interface is driven by two parallel effects. First, the bubble corona effect facilitates the generation of hydroxyl radicals capable of oxidizing luminol while the bubble is attached to the surface. Second, hypochlorite generated from chlorine sustains luminol emission for over 200 s and extends the emission range up to 5 mm into the solution, following bubble detachment. The new approach can increase the emission intensity of luminol-based assays 5-fold compared to the conventional method. This is demonstrated through a glucose bioassay, using a midrange mobile phone camera for detection. These findings significantly expand the potential applications of ECL by extending its effective range in time and space.

Fecal microbiota transplantation ameliorates high-fat diet-induced memory impairment in mice.

Gut dysbiosis is linked to metabolic and neurodegenerative diseases and comprises a plausible link between high-fat diet (HFD) and brain dysfunction. Here we show that gut microbiota modulation by either antibiotic treatment for 5 weeks or a brief 3-day fecal microbiota transplantation (FMT) regimen from low-fat (control) diet-fed mice decreased weight gain, adipose tissue hypertrophy, and glucose intolerance induced by HFD in C57BL/6 male mice. Notably, gut microbiota modulation by FMT completely reversed impaired recognition memory induced by HFD, whereas modulation by antibiotics had less pronounced effect. Improvement in recognition memory by FMT was accompanied by decreased HFD-induced astrogliosis in the hippocampal cornu ammonis region. Gut microbiome composition analysis indicated that HFD diminished microbiota diversity compared to control diet, whereas FMT partially restored the phyla diversity. Our findings reinforce the role of the gut microbiota on HFD-induced cognitive impairment and suggest that modulating the gut microbiota may be an effective strategy to prevent metabolic and cognitive dysfunction associated with unfavorable dietary patterns.

Neonatal limited bedding and nesting experience may lead to a sex-dependent increase in panic-like defensive behaviours in adult mice.

In humans, adverse physical and/or psychological traumas in childhood may predispose to developing psychiatric disorders in adulthood, including panic disorder. To model early life adversity in mice, we subjected male and female C57BL/6 J mice to a limited bedding and nesting (LBN) protocol between postnatal days 2-9 and investigated its effect on responsiveness to panicogenic challenges in adulthood. Panic-like escape behaviour was assessed during exposure to a high concentration of CO2 (20%) or in the beetle mania task (BMT), used to model respiratory and non-respiratory-related types of panic respectively. Neonatal exposure to LBN increased panic-like jumping during the CO2 challenge in male but not female mice. In an initial pharmacological validation of the BMT as a panic-inducing paradigm, undirected jumping and horizontal escape behaviours were reduced significantly by the panicolytic alprazolam (0.05 and 0.1mg.kg-1 i.p.) whilst tolerance to the close proximity of the aversive robo-beetle increased. The anxiolytic diazepam (1 mg.kg-1 i.p.) reduced only the number of horizontal escape attempts. In both sexes, previous experience of LBN significantly enhanced the number of horizontal escape episodes, indicating a pro-panic phenotype. Directed escape to access a safe ledge on the wall of the test arena, which was seen only in males, was also reduced significantly following LBN. These findings indicate that early life adversity produced by fragmented and unpredictable maternal care promotes a sex-specific increase in susceptibility to panic-like behaviour in adulthood. Whilst non-respiratory-related panic-like behaviour was enhanced in both sexes, females were resilient to respiratory-related challenges.

Global Prevalence of Pancreatic Cystic Lesions in the General Population on Magnetic Resonance Imaging: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Understanding the burden of pancreatic cystic lesions (PCLs) in the general population is important for clinicians and policymakers. In this systematic review, we sought to estimate the global prevalence of PCLs using magnetic resonance imaging (MRI) and to investigate factors that contribute to its variation. METHODS: We searched MEDLINE, EMBASE, and Cochrane Central, from database inception through February 2023. We included full-text articles that reported the prevalence of PCLs using MRI in the general population. A proportional meta-analysis was performed, and the prevalence of PCLs was pooled using a random-effects model. RESULTS: Fifteen studies with 65,607 subjects were identified. The pooled prevalence of PCLs was 16% (95% confidence interval [CI], 13%-18%; I2 = 99%), most of which were under 10 mm. Age-specific prevalence of PCLs increased from 9% (95% CI, 7%-12%) at 50 to 59 years, to 18% (95% CI, 14%-22%) at 60 to 69 years, 26% (95% CI, 20%-33%) at 70 to 79 years, and 38% at 80 years and above (95% CI, 25%-52%). There was no difference in prevalence between sexes. Subgroup analysis showed higher PCL prevalence when imaging findings were confirmed by independent radiologist(s) (25%; 95% CI, 16%-33%) than when chart review alone was used (5%; 95% CI, 4%-7%; P < .01). There was no independent association of PCL prevalence with geographic location (Europe, North America, or Asia), MRI indication (screening vs evaluation of non-pancreatic pathology), enrollment period, sample size, magnet strength (1.5 vs 3 tesla), and MRI sequence (magnetic resonance cholangiopancreatography vs no magnetic resonance cholangiopancreatography). CONCLUSION: In this systematic review, the global prevalence of PCLs using a highly sensitive noninvasive imaging modality ranged between 13% and 18%.

Impact of nitrogen fertilizer sustainability on corn crop yield: the role of beneficial microbial inoculation interactions.

BACKGROUND: Considering the challenges posed by nitrogen (N) pollution and its impact on food security and sustainability, it is crucial to develop management techniques that optimize N fertilization in croplands. Our research intended to explore the potential benefits of co-inoculation with Azospirillum brasilense and Bacillus subtilis combined with N application rates on corn plants. The study focused on evaluating corn photosynthesis-related parameters, oxidative stress assay, and physiological nutrient use parameters. Focus was placed on the eventual improved capacity of plants to recover N from applied fertilizers (AFR) and enhance N use efficiency (NUE) during photosynthesis. The two-year field trial involved four seed inoculation treatments (control, A. brasilense, B. subtilis, and A. brasilense + B. subtilis) and five N application rates (0 to 240 kg N ha-1, applied as side-dress). RESULTS: Our results suggested that the combined effects of microbial consortia and adequate N-application rates played a crucial role in N-recovery; enhanced NUE; increased N accumulation, leaf chlorophyll index (LCI), and shoot and root growth; consequently improving corn grain yield. The integration of inoculation and adequate N rates upregulated CO2 uptake and assimilation, transpiration, and water use efficiency, while downregulated oxidative stress. CONCLUSIONS: The results indicated that the optimum N application rate could be reduced from 240 to 175 kg N ha-1 while increasing corn yield by 5.2%. Furthermore, our findings suggest that replacing 240 by 175 kg N ha-1 of N fertilizer (-65 kg N ha-1) with microbial consortia would reduce CO2 emission by 682.5 kg CO2 -e ha-1. Excessive N application, mainly with the presence of beneficial bacteria, can disrupt N-balance in the plant, alter soil and bacteria levels, and ultimately affect plant growth and yield. Hence, highlighting the importance of adequate N management to maximize the benefits of inoculation in agriculture and to counteract N loss from agricultural systems intensification.

CRISPR and CRISPR-MVLST reveal conserved spacer distribution and high similarity among Salmonella enterica serovar Infantis genomes from Brazil and other countries.

Salmonella enterica serovar Infantis (S. Infantis) is a globally distributed non-typhoid serovar infecting humans and food-producing animals. Considering the zoonotic potential and public health importance of this serovar, strategies to characterizing, monitor and control this pathogen are of great importance. This study aimed to determine the genetic relatedness of 80 Brazilian S. Infantis genomes in comparison to 40 non-Brazilian genomes from 14 countries using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-Multi-Locus Virulence Sequence Typing (CRISPR-MVLST). CRISPR spacers were searched using CRISPR-Cas++ and fimH and sseL alleles using BLAST and MEGA X. Results were analyzed using BioNumerics 7.6 in order to obtain similarity dendrograms. A total of 23 CRISPR1 and 11 CRISPR2 alleles formed by 37 and 26 types of spacers, respectively, were detected. MVLST revealed the presence of five fimH and three sseL alleles. CRISPR's similarity dendrogram showed 32 strain subtypes, with an overall similarity ≥ 78.6. The CRISPR-MVLST similarity dendrogram showed 37 subtypes, with an overall similarity ≥ 79.2. In conclusion, S. Infantis strains isolated from diverse sources in Brazil and other countries presented a high genetic similarity according to CRISPR and CRISPR-MVLST, regardless of their source, year, and/or place of isolation. These results suggest that both methods might be useful for molecular typing S. Infantis strains using WGS data.

Metabolic dysfunction induced by HFD + L-NAME preferentially affects hippocampal mitochondria, impacting spatial memory in rats.

High-fat diet-induced metabolic changes are not restricted to the onset of cardiovascular diseases, but also include effects on brain functions related to learning and memory. This study aimed to evaluate mitochondrial markers and function, as well as cognitive function, in a rat model of metabolic dysfunction. Eight-week-old male Wistar rats were subjected to either a control diet or a two-hit protocol combining a high fat diet (HFD) with the nitric oxide synthase inhibitor L-NAME in the drinking water. HFD plus L-NAME induced obesity, hypertension, and increased serum cholesterol. These rats exhibited bioenergetic dysfunction in the hippocampus, characterized by decreased oxygen (O2) consumption related to ATP production, with no changes in H2O2 production. Furthermore, OPA1 protein expression was upregulated in the hippocampus of HFD + L-NAME rats, with no alterations in other morphology-related proteins. Consistently, HFD + L-NAME rats showed disruption of performance in the Morris Water Maze Reference Memory test. The neocortex did not exhibit either bioenergetic changes or alterations in H2O2 production. Calcium uptake rate and retention capacity in the neocortex of HFD + L-NAME rats were not altered. Our results indicate that hippocampal mitochondrial bioenergetic function is disturbed in rats exposed to a HFD plus L-NAME, thus disrupting spatial learning, whereas neocortical function remains unaffected.

Evaluation of enterovirus concentration, species identification, and cerebrospinal fluid parameters in patients of different ages with aseptic meningitis in São Paulo, Brazil.

Human enteroviruses (EV) are the most common cause of aseptic meningitis worldwide. Data on EV viral load in cerebrospinal fluid (CSF) and related epidemiological studies are scarce in Brazil. This study investigated the influence of EV viral load on CSF parameters, as well as identifying the involved species. CSF samples were collected in 2018-2019 from 140 individuals at The Hospital das Clínicas, São Paulo. The EV viral load was determined using real-time quantitative polymerase chain reaction, while EV species were identified by 5'UTR region sequencing. Median viral load was 5.72 log10 copies/mL and did not differ by subjects' age and EV species. Pleocytosis was observed in 94.3% of cases, with the highest white blood cell (WBC) counts in younger individuals. Viral load and WBC count were correlated in children (p = 0.0172). Elevated lactate levels were observed in 60% of cases and correlated with the viral load in preteen-teenagers (p = 0.0120) and adults (p = 0.0184). Most individuals had normal total protein levels (70.7%), with higher in preteen-teenagers and adults (p < 0.0001). By sequencing, 8.2% were identified as EV species A and 91.8% as species B. Age-specific variations in CSF characteristics suggest distinct inflammatory responses in each group.

Repeatome evolution across space and time: Unravelling repeats dynamics in the plant genus Erythrostemon Klotzsch (Leguminosae Juss).

Fluctuations in genomic repetitive fractions (repeatome) are known to impact several facets of evolution, such as ecological adaptation and speciation processes. Therefore, investigating the divergence of repetitive elements can provide insights into an important evolutionary force. However, it is not clear how the different repetitive element clades are impacted by the different factors such as ecological changes and/or phylogeny. To discuss this, we used the Neotropical legume genus Erythrostemon (Caesalpinioideae) as a model, given its ancient origin (~33 Mya), lineage-specific niche conservatism, macroecological heterogeneity, and disjunct distribution in Meso- and South American (MA and SA respectively) lineages. We performed a comparative repeatomic analysis of 18 Erythrostemon species to test the impact of environmental variables over repeats diversification. Overall, repeatome composition was diverse, with high abundances of satDNAs and Ty3/gypsy-Tekay transposable elements, predominantly in the MA and SA lineages respectively. However, unexpected repeatome profiles unrelated to the phylogeny/biogeography were found in a few MA (E. coccineus, E. pannosus and E. placidus) and SA (E. calycinus) species, related to reticulate evolution and incongruence between nuclear and plastid topology, suggesting ancient hybridizations. The plesiomorphic Tekay and satDNA pattern was altered in the MA-sensu stricto subclade with a striking genomic differentiation (expansion of satDNA and retraction of Tekay) associated with the colonization of a new environment in Central America around 20 Mya. Our data reveal that the current species-specific Tekay pool was the result of two bursts of amplification probably in the Miocene, with distinct patterns for the MA and SA repeatomes. This suggests a strong role of the Tekay elements as modulators of the genome-environment interaction in Erythrostemon, providing macroevolutionary insights about mechanisms of repeatome differentiation and plant diversification across space and time.

The Clade Replacement Theory: a framework to study age-dependent extinction.

There is no scientific consensus about whether and how species' evolutionary age, or the elapsed time since their origination, might affect their probability of going extinct. Different age-dependent extinction (ADE) patterns have been proposed in theoretical and empirical studies, while the existence of a consistent and universal pattern across the tree of life remains debated. If evolutionary age predicts species extinction probability, then the study of ADE should comprise the elapsed time and the ecological process acting on species from their origin to their extinction or to the present for extant species. Additionally, given that closely related species share traits associated with fitness, evolutionary proximity could generate similar ADE patterns. Considering the historical context and extinction selectivity based on evolutionary relatedness, we build on previous theoretical work to formalize the Clade Replacement Theory (CRT) as a framework that considers the ecological and evolutionary aspects of species age and extinction probability to produce testable predictions on ADE patterns. CRT's domain is the diversification dynamics of two or more clades competing for environmental space throughout time, and its propositions or derived hypotheses are as follows: (i) incumbency effects by an early arriving clade that limit the colonization and the diversification of a younger clade leading to a negative ADE scenario (younger species more prone to extinction than older ones) and (ii) an ecological shift triggered by an environmental change that imposes a new selective regime over the environmental space and leads to a positive ADE scenario (extinction probability increasing with age). From these propositions, we developed the prediction that the ADE scenario would be defined by whether an ecological shift happens or not. We discuss how the CRT could be tested with empirical data and provide examples where it could be applied. We hope this article will provide a common ground to unify results from different fields and foster new empirical tests of the mechanisms derived here while providing insights into CRT theoretical structuration.

Chemotherapeutic Mechanism of Action of the Synthetic Resorcinolic Methyl 3,5-dimethoxy-2-octanoylbenzoate.

Resorcinolic lipids are described as potential examples of selective chemotherapeutic adjuvants that can enhance the effects of cyclophosphamide (CYC) while promoting cell death without causing DNA damage. Therefore, the current study attempted to describe how the resorcinolic lipid methyl 3,5-dimethoxy-2-octanoylbenzoate (AMS35BB) interacted with DNA (DNA docking) and how this compound affected genetic toxicology models and other biological characteristics when combined with CYC. We observed that AMS35BB, used alone (7.5 and 10 mg/kg), increases the frequency of genomic damage (comet assay) but not chromosomal damage (micronuclei assay), lowers phagocytosis, and promotes cell death in Swiss male mice. When used in association with CYC, AMS35BB can reduce the risk of genomic damage by up to 33.8% as well as chromosomal damage, splenic phagocytosis, cell death, and lymphocyte frequency. Molecular docking showed that AMS35BB had a higher affinity than the active metabolite of CYC for binding to the DNA double helix major groove. As a result, AMS35BB has the potential to be both an adjuvant when used in association with CYC and a therapeutic candidate for the development of a selective chemotherapeutic drug.

Sleep timing behaviour, sleep duration and adherence to obesogenic dietary patterns from pre-school to school age: results from the Portuguese birth cohort Generation XXI.

In an obesogenic environment, short sleeping may increase opportunistic eating. The timing of sleep might also influence the drive to eat. This study investigated the prospective association of sleep timing and duration with diet in 5286 children from the Portuguese birth cohort Generation XXI, evaluated at 4 and 7 years of age. At 4 years, sleep duration was categorised into ≤10 and >10 h. Four sleep timing categories were generated based on the median split for sleep-onset and -offset times: 'Early Sleep-Early Wake'; 'Early Sleep-Late Wake'; 'Late Sleep-Early Wake'; 'Late Sleep-Late Wake'. At 7 years, diet was obtained by a food frequency questionnaire and three dietary patterns were included: 'Healthier', 'Energy-Dense Foods (EDF)' and 'Snacking'. The Healthy Eating Index was used to evaluate diet quality. Multinomial logistic regression models and generalised linear models were performed. Children who had a late sleep, independently of the time of waking up, had higher odds of following the 'EDF' pattern, compared with the 'Healthier'. Boys who had late sleep and/or late wake had also higher odds of following the 'Snacking' pattern and had poorer diet quality. In both sexes, a late sleep or late wake were associated with a lower diet quality, compared to the group 'Early Sleep-Early Wake', and independently of nap behaviour. In boys, shorter sleep duration was associated with a poorer diet. In conclusion, pre-schoolers with late bedtimes or wake-up times have worse dietary patterns and poorer diet quality at the age of 7 years, which seems to be independent of sleep duration.

Identifying time-resolved features of nocturnal sleep characteristics of narcolepsy using machine learning.

The differential diagnosis of narcolepsy type 1, a rare, chronic, central disorder of hypersomnolence, is challenging due to overlapping symptoms with other hypersomnolence disorders. While recent years have seen significant growth in our understanding of nocturnal polysomnography narcolepsy type 1 features, there remains a need for improving methods to differentiate narcolepsy type 1 nighttime sleep features from those of individuals without narcolepsy type 1. We aimed to develop a machine learning framework for identifying sleep features to discriminate narcolepsy type 1 from clinical controls, narcolepsy type 2 and idiopathic hypersomnia. The population included polysomnography data from 350 drug-free individuals (114 narcolepsy type 1, 90 narcolepsy type 2, 105 idiopathic hypersomnia, and 41 clinical controls) collected at the National Reference Centers for Narcolepsy in Montpelier, France. Several sets of nocturnal sleep features were explored, as well as the value of time-resolving sleep architecture by analysing sleep per quarter-night. Several patterns of nighttime sleep evolution emerged that differed between narcolepsy type 1, clinical controls, narcolepsy type 2 and idiopathic hypersomnia, with increased nighttime instability observed in patients with narcolepsy type 1. Using machine learning models, we identified rapid eye movement sleep onset as the best single polysomnography feature to distinguish narcolepsy type 1 from controls, narcolepsy type 2 and idiopathic hypersomnia. By combining multiple feature sets capturing different aspects of sleep across quarter-night periods, we were able to further improve between-group discrimination and could identify the most discriminative sleep features. Our results highlight salient polysomnography features and the relevance of assessing their time-dependent changes during sleep that could aid diagnosis and measure the impact of novel therapeutics in future clinical trials.

Effect of Hypertonic Saline Solution on the Ventilatory Mechanics of Lungs Donated After Brain Death.

INTRODUCTION: Brain death (BD) compromises the viability of the lung for donation. Hypertonic saline solution (HSS) induces rapid intravascular volume expansion and immunomodulatory action. We investigated its role in ventilatory mechanics (VMs) and in the inflammatory activity of the lungs of rats subjected to BD. METHODS: Wistar rats were divided into four groups: control, n = 10: intact rats subjected to extraction of the heart-lung block; BD, n = 8 (BD): rats treated with isotonic saline solution (4 mL/kg) immediately after BD; hypertonic saline 0 h, n = 9 (Hip.0'): rats treated with HSS (4 mL/kg) immediately after BD; and hypertonic saline 1 h, n = 9 (Hip.60'), rats treated with HSS (4 mL/kg) 60 min after BD. The hemodynamic characteristics, gas exchange, VMs, inflammatory mediators, and histopathological evaluation of the lung were evaluated over 240 min of BD. RESULTS: In VMs, we observed increased airway resistance, tissue resistance, tissue elastance, and respiratory system compliance in the BD group (P < 0.037), while the treated groups showed no impairment over time (P > 0.05). In the histological analysis, the BD group showed a greater area of perivascular edema and a higher neutrophil count than the control group and the Hip.60' group (P < 0.05). CONCLUSIONS: Treatment with HSS was effective in preventing changes in the elastic and resistive pulmonary components, keeping them at baseline levels. Late treatment reduced perivascular and neutrophilic edema in lung tissue.

Exploratory analysis of new craniometric measures for the investigation of biological sex using open-access statistical and machine-learning tools on a cone-beam computed tomography sample.

Investigation of the biological sex of human remains is a crucial aspect of physical anthropology. However, due to varying states of skeletal preservation, multiple approaches and structures of interest need to be explored. This research aims to investigate the potential use of distances between bifrontal breadth (FMB), infraorbital foramina distance (IOD), nasal breadth (NLB), inter-canine width (ICD), and distance between mental foramina (MFD) for combined sex prediction through traditional statistical methods and through open-access machine-learning tools. Ethical approval was obtained from the ethics committee, and out of 100 cone beam computed tomography (CBCT) scans, 54 individuals were selected with all the points visible. Ten extra exams were chosen to test the predictors developed from the learning sample. Descriptive analysis of measurements, standard deviation, and standard error were obtained. T-student and Mann-Whitney tests were utilized to assess the sex differences within the variables. A logistic regression equation was developed and tested for the investigation of the biological sex as well as decision trees, random forest, and artificial neural networks machine-learning models. The results indicate a strong correlation between the measurements and the sex of individuals. When combined, the measurements were able to predict sex using a regression formula or machine learning based models which can be exported and added to software or webpages. Considering the methods, the estimations showed an accuracy rate superior to 80% for males and 82% for females. All skulls in the test sample were accurately predicted by both statistical and machine-learning models. This exploratory study successfully established a correlation between facial measurements and the sex of individuals, validating the prediction potential of machine learning, augmenting the investigative tools available to experts with a high differentiation potential.

Translation, transcultural adaptation, and validation of PedsQL 3.0 Sickle Cell Disease Module into Brazilian Portuguese.

INTRODUCTION: Despite the high prevalence of sickle cell disease (SCD) in Brazil, no studies have described the validation of an SCD-specific health-related quality-of-life (HRQoL) instrument in children. We validated PedsQL 3.0 Sickle Cell Disease Module (PedsQL-SCD) for Brazilian Portuguese, and cross-validated it with PedsQL 4.0 Generic Core Scale (PedsQL-GCS) in children with SCD. METHODS: PedsQL-SCD was translated and culturally adapted using forward and reverse translations. PedsQL-SCD and PedsQL-GCS were tested in children and adolescents with SCD aged 2-18 years and their caregivers. Validity was assessed using the Pearson and intraclass correlation coefficients, and reliability measured with Cronbach's alpha. RESULTS: PedsQL-SCD was validated in 206 children with SCD (median age 14 years, range: 8-18) and 201 caregivers. Among patients and caregivers, the mean total score for PedsQL-SCD was 65.7 and 64.1, respectively. The mean total score for PedsQL-GCS was 73.1 and 68.9 among patients and caregivers, respectively. The internal consistency for PedsQL-SCD and PedsQL-GCS was good; Cronbach's alpha coefficients ranged from .59-.93 to .64-.83 among patients and from .60-.95 to .65-.85 among caregivers, respectively. Most intercorrelations between PedsQL-SCD and PedsQL-GCS, for patients and caregivers, had medium to large effect sizes (range: .23-.63 and .27-.64, respectively). Pain and pain impact domains of PedsQL-SCD and physical dimension of PedsQL-GCS had the highest cross-correlation (.63 and .6 for patients; .63 and .64 for caregivers, respectively), confirming convergent construct validity. CONCLUSION: PedsQL-SCD is a valid, culturally appropriate measure to assess HRQoL in children with SCD in Brazil and is well-correlated PedsQL-GCS.