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Abstract A 3-dimensional model of the angular contact ball bearing (ACBB) was modeled using Abaqus/standard (Dassault systems- version 2017) to investigate the influence of race thickness on the bearing performance. It was found that the ability to support higher contact stress increased with race thickness. However, large deformations were found to occur on outer race with thickness of 3.3 mm and only small deformations were observed on outer race with a thickness of 9.9 mm. The large deformations induce higher shear stresses on thin races than on thick races. These stresses cause spall growth in bearings and propagate into a network of cracks. As a result of these findings, thin races are prone to failure compared with thick races.

Summary: Background: Chagas disease (CD), endemic in 21 Latin American countries, has gradually spread beyond its traditional borders due to migratory movements and emerging as a global health concern. We conducted a systematic review and meta-analysis of available data to establish updated prevalence estimates of CD in Latin American migrants residing in non-endemic countries. Methods: A systematic search was conducted in MEDLINE/PubMed, Embase, Cochrane Library, Scopus, Web of Science, and LILACS via Virtual Health Library (Biblioteca Virtual em Saúde - BVS), including references published until November 1st, 2023. Pooled prevalence estimates and 95% confidence intervals (CI) were calculated using random effect models. Heterogeneity was assessed by the chi-square test and the I2 statistic. Subgroup analyses were performed to explore potential sources of heterogeneity among studies. The study was registered in the PROSPERO database (CRD42022354237). Findings: From a total of 1474 articles screened, 51 studies were included. Studies were conducted in eight non-endemic countries (most in Spain), between 2006 and 2023, and involving 82,369 screened individuals. The estimated pooled prevalence of CD in Latin American migrants living in non-endemic countries was 3.5% (95% CI: 2.5–4.7; I2: 97.7%), considering studies in which screening was indicated simply because the person was Latin American. Per subgroups, the pooled CD prevalence was 11.0% (95% CI: 7.7–15.5) in non-targeted screening (unselected population in reference centers) (27 studies); in blood donors (4 studies), the pooled prevalence was 0.8% (95% CI: 0.2–3.4); among people living with HIV Latin American immigrants (4 studies) 2.4% (95% CI: 1.4–4.3) and for Latin American pregnant and postpartum women (14 studies) 3.7% (95 CI: 2.4–5.6). The pooled proportion of congenital transmission was 4.4% (95% CI: 3.3–5.8). Regarding the participants’ country of origin, 7964 were from Bolivia, of which 1715 (21,5%) were diagnosed with CD, and 21,304 were from other Latin American countries of which 154 (0,72%) were affected. Interpretation: CD poses a significant burden of disease in Latin American immigrants in non-endemic countries, suggesting that CD is no longer a problem limited to the American continent and must be considered as a global health challenge. Funding: This study was funded by the World Heart Federation, through a research collaboration with Novartis Pharma AG.

Abstract We aimed to find new therapeutic targets related to Cancer Stem Cell alterations in recurrent patients from two TCGA cohorts: Testicular Germ Cell Tumor (TGCT) and Uterine Corpus Endometrial Carcinoma (UCEC). Raw sequencing data were downloaded from the TCGA database. Datasets containing RNA expression and Methylation files were directly downloaded from cBioportal. Variant Call Format files (VCFs) were downloaded from the GDC portal. Gene enrichment analysis was performed using GSEA (Gene Set Enrichment Analysis) software. Transcriptome profiling, coexpression co-occurrence, networks, and survival analyses were performed using cBioportal tools, while mutational analysis of patients was processed using UNIX scripts. We found that cancer stem cell transcription factors were highly expressed in Testicular Germ Cell Tumor (TGCT) and Uterine Corpus Endometrial Carcinoma (UCEC) cohorts, compared to the other 29 cancer cohorts in TCGA. Patients presented a poorer diagnosis when the genes (POU5F1, NANOG, SOX2, SALL4, ABCB1, ABCC1, and ABCG2) were altered. In UCEC cohorts, recurrent patients showed the ABCG2 potentially phosphorylated by the PIM1 kinase. In the TGCT cohort, genes ABCB1 and ABCG2 only appeared in the phosphonetwork in recurrent patients potentially phosphorylated by the same kinase, PIM1, but also by PRKACA. Our data indicate that PRKACA and PIM1 may modulate POU5F1 phosphorylation.

Abstract miR-Blood is a high-quality, small RNA expression atlas for the major components of human peripheral blood (plasma, erythrocytes, thrombocytes, monocytes, neutrophils, eosinophils, basophils, natural killer cells, CD4+ T cells, CD8+ T cells, and B cells). Based on the purified blood components from 52 individuals, the dataset provides a comprehensive repository for the expression of 4971 small RNAs from eight non-coding RNA classes.

Abstract This manuscript presents the quantification and correlation of three aspects of Alzheimer’s Disease evolution, including structural, biochemical, and cognitive assessments. We aimed to test a novel structural biomarker for neurodegeneration based on a cortical folding model for mammals. Our central hypothesis is that the cortical folding variable, representative of axonal tension in white matter, is an optimal discriminator of pathological aging and correlates with altered loadings in Cerebrospinal Fluid samples and a decline in cognition and memory. We extracted morphological features from T1w 3T MRI acquisitions using FreeSurfer from 77 Healthy Controls (age = 66 ± 8.4, 69% females), 31 Mild Cognitive Impairment (age = 72 ± 4.8, 61% females), and 13 Alzheimer’s Disease patients (age = 77 ± 6.1, 62% females) of recruited volunteers in Brazil to test its discriminative power using optimal cut-point analysis. Cortical folding distinguishes the groups with reasonable accuracy (Healthy Control-Alzheimer’s Disease, accuracy = 0.82; Healthy Control-Mild Cognitive Impairment, accuracy = 0.56). Moreover, Cerebrospinal Fluid biomarkers (total Tau, A $$\beta $$ β 1-40, A $$\beta $$ β 1-42, and Lipoxin) and cognitive scores (Cognitive Index, Rey’s Auditory Verbal Learning Test, Trail Making Test, Digit Span Backward) were correlated with the global neurodegeneration in MRI aiming to describe health, disease, and the transition between the two states using morphology.

ABSTRACT Purpose: Sling as a therapeutic option for male stress urinary incontinence (SUI) has been reviewed in the last two decades, as it is a relatively simpliest surgery compared to artificial urinary sphincter and has the ability to modulate urethral compression. This study aims to evaluate the efficacy, rate of complications, quality of life and the effects on bladder emptying of the Argus T® compressive and ajustable sling in moderate and severe male SUI treatment. Materials and Methods: Men eligible for stress urinary incontinence treatment after radical prostatectomy were recruited and prospectively evaluated, from March 2010 to November 2016. It was selected outpatient men with moderate and severe SUI, after 12 months of radical prostatectomy, who have failed conservative treatment. All patients had a complete clinical and urodynamic pre and post treatment evaluation, by means of clinical history, physical examination, urine culture, 1-hour pad test and ICIq-SF questionnaire. The UDS was performed after 12, 18 and 24 months postoperatively. Results: Thirty-seven men underwent sling surgery, 19 patients (51.4%) with moderate and 18 (48.6%) with severe SUI. The minimum follow-up time was 5 years. Overall, we had a success rate of 56.7% at 60 months follow-up. After surgery, we did not observe significant changes in the urodynamic parameters evaluated during the follow-up. No patient had urodynamic bladder outlet obstruction (BOO) after sling implantation. Readjustment of the Argus T® sling was performed in 16 (41%) of the patients and 51% of the patients reported some adverse event. Conclusion: We demonstrate a long-term efficacy and safety of Sling Argus T® as an alternative to moderate and severe male SUI treatment. Furthermore, in our study bulbar urethra compression does not lead to bladder outlet obstruction.

Objective: To assess how inadequate reporting of cointerventions influences estimated treatment effects in recent cardiovascular trials. Methods: Medline/Embase were systematically searched from January 1, 2011 to July 1, 2021 for trials evaluating pharmacologic interventions on clinical cardiovascular outcomes published in 5 high-impact journals. Information on adequate vs inadequate reporting of cointerventions, blinding, risk of bias due to deviations of intended interventions (low vs high/some concerns), funding (nonindustry vs industry), design (superiority vs noninferiority), and results were assessed by 2 reviewers. The association with effect sizes was assessed using meta-regression random-effect analysis, expressed as ratios of odds ratios (ROR). RORs of >1.0 indicated that trials with the methodological factor pointing to lower quality report larger treatment estimates. Results: In total, 164 trials were included. Of the 164 trials, 124 (74%) did not adequately report cointerventions; 89 of the 164 trials (54%) provided no information regarding cointerventions, and 70 of the 164 (43%) were at risk of bias due to inadequate blinding. Moreover, 86 of the 164 (53%) were at risk of bias due to deviation of intended interventions. Of the 164 trials, 144 (88%) were funded by the industries. Trials with inadequate reporting of cointerventions had larger treatment estimates for the primary end point (ROR, 1.08; 95% CI, 1.01-1.15; I2=0%). No significant association with results for blinding (ROR, 0.97; 95% CI, 0.91-1.03; I2=66%), deviation of intended interventions (ROR, 0.98; 95% CI, 0.92-1.04; I2=0%), or funding (ROR, 1.01; 95% CI, 0.93-1.09; I2=0%) was found. Conclusion: We conclude that trials with inadequate reporting of cointerventions showed larger treatment effect estimates, potentially indicating overestimation of therapeutic benefit. Trial Registration: Prospero Identifier: CRD42017072522

Abstract Stress freezing is an important and powerful procedure in 3-dimensional experimental stress analysis using photoelasticity. The application of the stress freezing technique to extract stress components from loaded engineering structures has, however, declined over the years even though its principles are well established. This is attributed to huge costs arising from energy consumption during the process. In addition, significant time is needed to generate the desired information from isoclinic and isochromatic fringes. To overcome the limitations of stress freezing in photoelasticity and transform it into an economical device for stress analysis in an engineering environment, a new stress freezing cycle that lasts 5 h is proposed. The proposed technique is used in several applications of elastomeric seals with different cross-sectional profiles to assess their suitability. It was found that reducing the cycle time can lead to huge energy savings without compromising the quality of the fringes. Moreover, the use of isochromatic only to extract stress components leads to a shorter processing time to achieve desirable information since the process of obtaining isoclinic data is involving. In this paper, results of stress analysis from stress-frozen elastomeric seals with various cross-sections using the new stress freezing cycle are presented.

Abstract Background Among critically ill patients with acute kidney injury (AKI), earlier initiation of renal replacement therapy (RRT) may mitigate fluid accumulation and confer better outcomes among individuals with greater fluid overload at randomization. Methods We conducted a pre-planned post hoc analysis of the STandard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial. We evaluated the effect of accelerated RRT initiation on cumulative fluid balance over the course of 14 days following randomization using mixed models after censoring for death and ICU discharge. We assessed the modifying effect of baseline fluid balance on the impact of RRT initiation strategy on key clinical outcomes. Patients were categorized in quartiles of baseline fluid balance, and the effect of accelerated versus standard RRT initiation on clinical outcomes was assessed in each quartile using risk ratios (95% CI) for categorical variables and mean differences (95% CI) for continuous variables. Results Among 2927 patients in the modified intention-to-treat analysis, 2738 had available data on baseline fluid balance and 2716 (92.8%) had at least one day of fluid balance data following randomization. Over the subsequent 14 days, participants allocated to the accelerated strategy had a lower cumulative fluid balance compared to those in the standard strategy (4509 (− 728 to 11,698) versus 5646 (0 to 13,151) mL, p = 0.03). Accelerated RRT initiation did not confer greater 90-day survival in any of the baseline fluid balance quartiles (quartile 1: RR 1.11 (95% CI 0.92 to 1.34), quartile 2: RR 1.03 (0.87 to 1.21); quartile 3: RR 1.08 (95% CI 0.91 to 1.27) and quartile 4: RR 0.87 (95% CI 0.73 to 1.03), p value for trend 0.08). Conclusions Earlier RRT initiation in critically ill patients with AKI conferred a modest attenuation of cumulative fluid balance. Nonetheless, among patients with greater fluid accumulation at randomization, accelerated RRT initiation did not have an impact on all-cause mortality. Trial registration: ClinicalTrials.gov number, https://clinicaltrials.gov/ct2/show/NCT02568722 , registered October 6, 2015.

Abstract Recent research has shown that criminal networks have complex organizational structures, but whether this can be used to predict static and dynamic properties of criminal networks remains little explored. Here, by combining graph representation learning and machine learning methods, we show that structural properties of political corruption, police intelligence, and money laundering networks can be used to recover missing criminal partnerships, distinguish among different types of criminal and legal associations, as well as predict the total amount of money exchanged among criminal agents, all with outstanding accuracy. We also show that our approach can anticipate future criminal associations during the dynamic growth of corruption networks with significant accuracy. Thus, similar to evidence found at crime scenes, we conclude that structural patterns of criminal networks carry crucial information about illegal activities, which allows machine learning methods to predict missing information and even anticipate future criminal behavior.

Introduction: Handheld echocardiography (echo) is the tool of choice for rheumatic heart disease (RHD) screening. We aimed to assess the agreement between screening and standard echo for latent RHD diagnosis in schoolchildren from an endemic setting. Methods: Over 14 months, 3 nonphysicians used handheld machines and the 2012 WHF Criteria to determine RHD prevalence in consented schoolchildren from Brazilian low-income public schools. Studies were interpreted by telemedicine by 3 experts (Brazil, US). RHD-positive children (borderline/definite) and those with congenital heart disease (CHD) were referred for standard echo, acquired and interpreted by a cardiologist. Agreement between screening and standard echo, by WHF subgroups, was assessed. Results: 1390 students were screened in 6 schools, with 110 (7.9%, 95% CI 6.5–9.5) being screen positive (14 ± 2 years, 72% women). Among 16 cases initially diagnosed as definite RHD, 11 (69%) were confirmed, 4 (25%) reclassified to borderline, and 1 to normal. Among 79 cases flagged as borderline RHD, 19 (24%) were confirmed, 50 (63%) reclassified to normal, 8 (10%) reclassified as definite RHD, and 2 had mild CHD. Considering the 4 diagnostic categories, kappa was 0.18. In patients with borderline RHD reclassified to non-RHD, the most frequent WHF criterion was B (isolated mitral regurgitation, 64%), followed by A (2 mitral valve morphological features, 31%). In 1 patient with definite RHD reclassified to normal, the WHF criterion was D (borderline RHD in aortic and mitral valves). After standard echo, RHD prevalence was 3.2% (95% CI 2.3–4.2). Conclusions: Although practical, RHD screening with handheld devices tends to overestimate prevalence.

Abstract Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation.

Abstract Corruption crimes demand highly coordinated actions among criminal agents to succeed. But research dedicated to corruption networks is still in its infancy and indeed little is known about the properties of these networks. Here we present a comprehensive investigation of corruption networks related to political scandals in Spain and Brazil over nearly three decades. We show that corruption networks of both countries share universal structural and dynamical properties, including similar degree distributions, clustering and assortativity coefficients, modular structure, and a growth process that is marked by the coalescence of network components due to a few recidivist criminals. We propose a simple model that not only reproduces these empirical properties but reveals also that corruption networks operate near a critical recidivism rate below which the network is entirely fragmented and above which it is overly connected. Our research thus indicates that actions focused on decreasing corruption recidivism may substantially mitigate this type of organized crime.

Abstract Immunotherapies have recently gained traction as highly effective therapies in a subset of late-stage cancers. Unfortunately, only a minority of patients experience the remarkable benefits of immunotherapies, whilst others fail to respond or even come to harm through immune-related adverse events. For immunotherapies within the PD-1/PD-L1 inhibitor class, patient stratification is currently performed using tumor (tissue-based) PD-L1 expression. However, PD-L1 is an accurate predictor of response in only ~30% of cases. There is pressing need for more accurate biomarkers for immunotherapy response prediction. We sought to identify peripheral blood biomarkers, predictive of response to immunotherapies against lung cancer, based on whole blood microRNA profiling. Using three well-characterized cohorts consisting of a total of 334 stage IV NSCLC patients, we have defined a 5 microRNA risk score (miRisk) that is predictive of overall survival following immunotherapy in training and independent validation (HR 2.40, 95% CI 1.37–4.19; P

Crop–livestock integrated systems such as intercropping and crop rotation have been critical for sustainable agriculture, promoting land use intensification throughout the year. The success of these systems under no-till depends on numerous factors, and the choice of forage grass is paramount. In this study, maize grain yield, forage dry matter yield, bromatological quality, and estimated meat production were assessed in a field experiment where maize (Zea mays L.) was intercropped with Guinea grass (Megathyrsus maximus cv. Tanzania) and palisade grass (Urochloa brizantha cv Marandu) under N rates from 0 to 270 kg ha−1. Nitrogen fertilization resulted in the highest forage dry matter yield, on average, 2.9-fold higher than the N-unfertilized treatments. The highest maize grain yield was obtained with 270 kg ha−1 of N, 48% higher than all other treatments. Guinea grass intercropped with maize and fertilized with 270 kg ha−1 of N resulted in an estimated meat production 27% higher than palisade grass at the same N rate. However, at the final cut, Guinea grass fertilized with 270 kg ha−1 of N led to the highest neutral detergent fiber, acid detergent fiber, and cellulose. While palisade grass seems to impose lower competition with maize, Guinea grass increases estimated meat production.

AimsTo evaluate clinical and electrocardiographic outcomes of patients with COVID-19, comparing those using chloroquine compounds (chloroquine) to individuals without specific treatment.MethodsOutpatients with suspected COVID-19 in Brazil who had at least one tele-electrocardiography (ECG) recorded in a telehealth system were enrolled in two arms (Group 1: chloroquine and Group 2: without specific treatment) and one registry (Group 3: other treatments). Outcomes were assessed through follow-up calls (phone contact, days 3 and 14) and linkage to national mortality and hospitalization databases. The primary outcome was composed of: hospitalization, intensive care admission, mechanical ventilation, and all-cause death, and the ECG outcome was the occurrence of major abnormalities by the Minnesota code. Significant variables in univariable logistic regression were included in 4 models: 1-unadjusted; 2-adjusted for age and sex; 3-model 2 + cardiovascular risk factors and 4-model 3 + COVID-19 symptoms.ResultsIn 303 days, 712 (10.2%) patients were allocated in group 1, 3,623 (52.1%) in group 2 and 2,622 (37.7%) in group 3; 1,969 had successful phone follow-up (G1: 260, G2: 871, and G3: 838). A late follow-up ECG was obtained for 917 (27.2%) patients [group 1: 81 (11.4%), group 2: 512 (14.1%), group 3: 334 (12.7%)]. In adjusted models, chloroquine was independently associated with greater chance of the composite clinical outcome: phone contact (model 4): OR = 3.24 (95% CI 2.31–4.54), p < 0.001. Chloroquine was also independently associated with higher mortality, assessed by phone + administrative data (model 3): OR = 1.67 (95% CI 1.20–2.28). However, chloroquine did not associate with the occurrence of major ECG abnormalities [model 3; OR = 0.80 (95% CI 0.63–1.02, p = 0.07)]. Abstracts with partial results of this work was accepted in the American Heart Association Scientific Sessions, November 2022, in Chicago, IL, USA.ConclusionChloroquine was associated with a higher risk of poor outcomes in patients suspected to have COVID-19 when compared to those who received standard care. Follow-up ECGs were obtained in only 13.2% of patients and did not show any significant differences in major abnormalities amongst the three groups. In the absence of early ECG changes, other side effects, late arrhythmias or deferral of care may be hypothesized to explain the worse outcomes.

Provision of shade reduces radiant heat load on feedlot cattle, thus reducing demand of water and energy for thermoregulation. While the positive effects of shade on animal welfare are widely known, the literature lacks data on the magnitude of its economic impacts. In this study, we propose the concept of novel shade design to prove that a correctly oriented and dimensioned roof structure, which optimizes shade to be displaced within the pens, motivates cattle to seek shade, protect them from short-wave solar radiation, and is resilient to counteract weather adverse conditions. The beneficial outcome is improvement in animal welfare and productive performance, as well as increments on financial return and sustainability. To attest these benefits, eight hundred B. indicus × Bos taurus bulls were randomly assigned in pens with or without shade from a galvanized steel-roof structure. Performance data (e.g., dry matter intake, body weight gain, feed efficiency and hot carcass weight) and heat stress indicators (e.g., subcutaneous temperature, body-surface temperature, respiratory rate and water intake) were assessed along the study period. The economic outcomes derived from shade implementation were determined using the net present value. Meteorological variables were also monitored every 1 min, and grouped in a thermal comfort index for feedlot cattle, the InComfort Index (InCI). The shade structure efficiently reduced radiant heat load on cattle in pens with shade. According to the classification of the InCI, during very hot days (InCI > 0.6; around noon with mean solar radiation above 800 W m−2 and mean air temperature above 33°C), greater proportion (80%) of animals in shaded pens were using shade. Under such circumstances, cattle in shade had water intake reduced by 3.4 L per animal, body temperature was lower by 5°C, subcutaneous temperature was lower by 1°C and respiration rate was lower by 10 breaths min−1 compared to animals in pens without shade (P = 0.0001). Although dry matter intake was similar (P = 0.6805), cattle in pens with shade had higher average daily gain reflected in a heavier hot carcass weight (8 kg animal−1; P = 0.0002). Considering an initial investment of $90 per animal to build a structure that lasts 15 years, the expected payback time is four finishing cycles (~110 days per cycle). In conclusion, this study confirms that the proposed novel shade design is economically profitable, improves performance, and enhances animal welfare.

Identification of febrile children at risk of death in low-resource settings can improve survival, but tools for their prompt recognition are lacking. Here, the authors show that sTREM-1 measured at clinical presentation predicts in-hospital mortality in febrile children in Uganda.

Category: Midfoot/Forefoot; Bunion Introduction/Purpose: The Original Lapidus procedure (OLP) consists of realigning the varus of the first metatarsal (M1) present in the hallux valgus (HV) deformities, by fusing the first tarsometatarsal joint (TMJ) and the M1 to the second metatarsal (M2). Compared to its modified version, some studies support that the OLP is more stable with less motion around the TMJ, which may prevent complications such as recurrence. However, fusion between M1 to M2 may not occur and its clinical and radiographic impact is still unknown. The aim of this study was to compare clinical, functional and radiographic outcomes in patients who underwent the OLP that evolved with and without fusion between the M1 and M2. Our null hypothesis was that they would have the same results. Methods: A retrospective and comparative study of twenty-nine patients (thirty-eight feet) with a mean follow-up of 18.03 (range, 6-51) months who underwent the OLP. They were divided in two different groups based on the presence of fusion and non-fusion between the M1 and M2 (Figure1). Twenty-three patients were included in the first group and fifteen in the second. Their average age was 48.74 (range,18-73) years. Twenty-five patients were female and four, male. Their mean body mass index (BMI) was 25.6 (range, 19.13-31.64). Clinical and functional data were assessed with the VAS for pain, AOFAS, LEFS and SF-12. SF- 12 comprises physical and mental health scales (PCS-12 and MCS-12). Radiographic parameters assessed were bony and soft tissue forefoot widths (BSFW), intermetatarsal-angle(IMA) and HV-angle(HVA). Intraclass Correlation Coefficients (ICC) were calculated for all radiographic measurements. Clinical, functional and radiographic measurements were compared between the two groups pre- and postoperatively using Student t Test. Results: The two groups were demographically similar in terms of mean age, BMI and follow-up time (p=.28, p=.84 and p=.06, respectively). Separately, patients from both groups presented significant improvements in all questionnaires (p

Category: Midfoot/Forefoot Introduction/Purpose: The Lapidus procedure (LP) is a powerful technique that often provides significant corrections of the hallux valgus (HV) deformities. In addition, it is described that forefoot width alters considerably with this technique, impacting in shoe wear. However, it has not yet been reported whether foot narrowing reflects on clinical and functional outcomes. This study aimed to evaluate the effect of variations in bony and soft tissue foot widths (BSFW) on clinical and functional outcomes after HV correction with the LP. Secondarily, we also tried to assess the relationship of standard radiographic measurements of HV with changes in BSFW. Methods: Forty-three feet in 35 patients with a mean follow-up of 18.5-months who underwent the LP were retrospectively reviewed. Bony width was measured from the most medial extent of the first metatarsal head to the most lateral extent of the fifth metatarsal head. Soft tissue width was measured considering the most medial and lateral shadow of the foot (Figure 1). Clinical and functional data were assessed with the VAS for pain, AOFAS, LEFS and SF-12. SF-12 comprises physical and mental health scales (PCS-12 and MCS-12). HV radiographic parameters as intermetatarsal-angle (IMA), HV-angle (HVA) and sesamoid- subluxation (SS) were assessed. Intraclass Correlation Coefficients (ICC) were calculated for BSFW. Clinical, functional and radiographic measurements were compared. Linear regression was used to assess the correlation of Δ-BSFW with clinical, functional and radiographic results. We also evaluated our sample at the cut-off point of quartile-50% to assess whether a given measure of Δ-BSFW was related to clinical and functional outcomes. Results: Pre- and postoperative ICC was 0.95 for bony and soft tissue width measurements. Bony width changed significantly from 95.5mm to 84.2mm (11.8%) and soft tissue width from 107.12mm to 100.84mm (5.86%) (p

Three different reservoir simulators that utilize both two-phase and three-phase microemulsion phase behavior models are used to model surfactant–polymer flooding to determine and compare their results. Different models are used in each simulator to describe the physical behavior of injected chemicals into the reservoir, which raises the need to benchmark their results. The physical behavior models of polymer and surfactant were constructed and verified on a 1D scale reservoir model and further verified in a 3D model. Finally, simulations were conducted in a field-scale reservoir containing 680,400 grids, where results were compared and analyzed. The 1D and 3D model results suggest an excellent match between the different simulators in modeling surfactant–polymer floods. In the case of the field-scale model, the simulators matched in terms of oil recovery and total volumes produced and injected, while having similar reservoir pressure profiles but with significant discrepancies in terms of injected and produced chemicals. These results indicate that despite the differences in the calculated injected and produced chemicals due to the different models in the simulators, the effect of surfactant–polymer floods on oil recovery, total injected and produced fluids, and average pressure profiles can be comparably modeled in all of the three simulators.

Abstract We propose herein a mathematical model to predict the COVID-19 evolution and evaluate the impact of governmental decisions on this evolution, attempting to explain the long duration of the pandemic in the 26 Brazilian states and their capitals well as in the Federative Unit. The prediction was performed based on the growth rate of new cases in a stable period, and the graphics plotted with the significant governmental decisions to evaluate the impact on the epidemic curve in each Brazilian state and city. Analysis of the predicted new cases was correlated with the total number of hospitalizations and deaths related to COVID-19. Because Brazil is a vast country, with high heterogeneity and complexity of the regional/local characteristics and governmental authorities among Brazilian states and cities, we individually predicted the epidemic curve based on a specific stable period with reduced or minimal interference on the growth rate of new cases. We found good accuracy, mainly in a short period (weeks). The most critical governmental decisions had a significant temporal impact on pandemic curve growth. A good relationship was found between the predicted number of new cases and the total number of inpatients and deaths related to COVID-19. In summary, we demonstrated that interventional and preventive measures directly and significantly impact the COVID-19 pandemic using a simple mathematical model. This model can easily be applied, helping, and directing health and governmental authorities to make further decisions to combat the pandemic.

Abstract Background Due to clinical and methodological diversity, clinical studies included in meta-analyses often differ in ways that lead to differences in treatment effects across studies. Meta-regression analysis is generally recommended to explore associations between study-level characteristics and treatment effect, however, three key pitfalls of meta-regression may lead to invalid conclusions. Our aims were to determine the frequency of these three pitfalls of meta-regression analyses, examine characteristics associated with the occurrence of these pitfalls, and explore changes between 2002 and 2012. Methods A meta-epidemiological study of studies including aggregate data meta-regression analysis in the years 2002 and 2012. We assessed the prevalence of meta-regression analyses with at least 1 of 3 pitfalls: ecological fallacy, overfitting, and inappropriate methods to regress treatment effects against the risk of the analysed outcome. We used logistic regression to investigate study characteristics associated with pitfalls and examined differences between 2002 and 2012. Results Our search yielded 580 studies with meta-analyses, of which 81 included meta-regression analyses with aggregated data. 57 meta-regression analyses were found to contain at least one pitfall (70%): 53 were susceptible to ecological fallacy (65%), 14 had a risk of overfitting (17%), and 5 inappropriately regressed treatment effects against the risk of the analysed outcome (6%). We found no difference in the prevalence of meta-regression analyses with methodological pitfalls between 2002 and 2012, nor any study-level characteristic that was clearly associated with the occurrence of any of the pitfalls. Conclusion The majority of meta-regression analyses based on aggregate data contain methodological pitfalls that may result in misleading findings.

Introduction: Patients with advanced, non-oncogene-driven NSCLC with high programmed death-ligand 1 (PD-L1) expression are eligible for treatment with immunotherapy. There is, however, an urgent medical need for biomarkers identifying cases that require additional combination with chemotherapy. We previously uncovered a myeloid-based 5-microRNA (miRNA) signature that identified responders to immunotherapy in PD-L1 unstratified patients; however, its potential utility in treatment guidance for patients with PD-L1 high tumors remained unclear. Methods: We trained (n = 68) and validated (n = 56) a 5-miRNA multivariable Cox proportional hazards model predictive of overall survival on small RNA sequencing data of whole blood samples prospectively collected before the commencement of immunotherapy for stage IV NSCLC with PD-L1 tumor proportion score greater than or equal to 50%, treated with PD-1 inhibitor monotherapy (immunotherapy alone [IO]). Specificity was demonstrated in a control cohort treated with immunochemotherapy (ICT) (n = 31). Results: The revised 5-miRNA risk score (miRisk) stratified IO-treated patients and identified a high-risk group with significantly shorter overall survival (hazard ratio = 5.24, 95% confidence interval: 2.17–12.66, p < 0.001). There was a significant interaction between the miRisk score and type of treatment (IO or ICT, p = 0.036), indicating that the miRisk score may serve as a predictive biomarker for immunotherapy response. Furthermore, the miRisk score could identify a group of high-risk patients who may benefit from treatment with ICT as opposed to IO (hazard ratio = 0.35, 95% confidence interval: 0.15–0.82, p = 0.018). Conclusions: The miRisk score can distinguish a group of patients with PD-L1 high, stage IV NSCLC likely to benefit from adding chemotherapy to immunotherapy and may support treatment decisions as a blood-based complementary diagnostic.

IntroductionHyperglycemia is associated with a higher cardiovascular risk, as evidenced by increased carotid-intima media thickness (CIMT) in youth with diabetes. We conducted a systematic review and meta-analysis to assess the effect of pharmacological or non-pharmacological interventions on CIMT in children and adolescents with prediabetes or diabetes.MethodsWe conducted systematic searches of MEDLINE, EMBASE, and CENTRAL, together with supplementary searches in trial registers and other sources for studies completed up to September 2019. Interventional studies assessing ultrasound CIMT in children and adolescents with prediabetes or diabetes were considered for inclusion. Where appropriate, data were pooled across studies using random-effect meta-analysis. Quality was assessed using The Cochrane Collaboration’s risk-of-bias tool and a CIMT reliability tool.ResultsSix studies involving 644 children with type 1 diabetes mellitus were included. No study involved children with prediabetes or type 2 diabetes. Three randomized controlled trials (RCTs) evaluated the effects of metformin, quinapril, and atorvastatin. Three non-randomized studies, with a before-and-after design, evaluated the effects of physical exercise and continuous subcutaneous insulin infusion (CSII). The mean CIMT at baseline ranged from 0.40 to 0.51 mm. The pooled difference in CIMT was -0.01 mm (95% CI: -0.04 to 0.01) for metformin compared to placebo (2 studies; 135 participants; I2: 0%). The difference in CIMT was -0.01 mm (95% CI: -0.03 to 0.01) for quinapril compared to placebo (1 study; 406 participants). The mean change from baseline in CIMT was -0.03 mm (95% CI: -0.14 to 0.08) after physical exercise (1 study; 7 participants). Inconsistent results were reported for CSII or for atorvastatin. CIMT measurement was rated at a higher quality on all reliability domains in 3 (50%) studies. The confidence in results is limited by the low number of RCTs and their small sample sizes, as well as the high risk of bias in before-and-after studies.ConclusionsSome pharmacological interventions may decrease CIMT in children with type 1 diabetes. However, there is great uncertainty with respect to their effects and no strong conclusions can be drawn. Further evidence from larger RCTs is required.Systematic Review RegistrationPROSPERO, CRD42017075169

Abstract Objectives To determine the effect of therapeutic anticoagulation, with low molecular weight heparin (LMWH) or unfractionated heparin (UFH, high dose nomogram), compared to standard care in hospitalized patients admitted for COVID-19 with an elevated D-dimer on the composite outcome of intensive care unit (ICU) admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death up to 28 days. Trial design Open-label, parallel, 1:1, phase 3, 2-arm randomized controlled trial Participants The study population includes hospitalized adults admitted for COVID-19 prior to the development of critical illness. Excluded individuals are those where the bleeding risk or risk of transfusion would generally be considered unacceptable, those already therapeutically anticoagulated and those who have already have any component of the primary composite outcome. Participants are recruited from hospital sites in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and the United States of America. The inclusion criteria are: 1) Laboratory confirmed COVID-19 (diagnosis of SARS-CoV-2 via reverse transcriptase polymerase chain reaction as per the World Health Organization protocol or by nucleic acid based isothermal amplification) prior to hospital admission OR within first 5 days (i.e. 120 hours) after hospital admission; 2) Admitted to hospital for COVID-19; 3) One D-dimer value above the upper limit of normal (ULN) (within 5 days (i.e. 120 hours) of hospital admission) AND EITHER: a. D-Dimer ≥2 times ULN OR b. D-Dimer above ULN and Oxygen saturation ≤ 93% on room air; 4) > 18 years of age; 5) Informed consent from the patient (or legally authorized substitute decision maker). The exclusion criteria are: 1) pregnancy; 2) hemoglobin 1.8 (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation); 6) patient already prescribed intermediate dosing of LMWH that cannot be changed (determination of what constitutes an intermediate dose is to be at the discretion of the treating clinician taking the local institutional thromboprophylaxis protocol for high risk patients into consideration); 7) patient already prescribed therapeutic anticoagulation at the time of screening [low or high dose nomogram UFH, LMWH, warfarin, direct oral anticoagulant (any dose of dabigatran, apixaban, rivaroxaban, edoxaban)]; 8) patient prescribed dual antiplatelet therapy, when one of the agents cannot be stopped safely; 9) known bleeding within the last 30 days requiring emergency room presentation or hospitalization; 10) known history of a bleeding disorder of an inherited or active acquired bleeding disorder; 11) known history of heparin-induced thrombocytopenia; 12) known allergy to UFH or LMWH; 13) admitted to the intensive care unit at the time of screening; 14) treated with non-invasive positive pressure ventilation or invasive mechanical ventilation at the time of screening; 15) Imminent death according to the judgement of the most responsible physician; 16) enrollment in another clinical trial of antithrombotic therapy involving hospitalized patients. Intervention and comparator Intervention: Therapeutic dose of LMWH (dalteparin, enoxaparin, tinzaparin) or high dose nomogram of UFH. The choice of LMWH versus UFH will be at the clinician’s discretion and dependent on local institutional supply. Comparator: Standard care [thromboprophylactic doses of LMWH (dalteparin, enoxaparin, tinzaparin, fondaparinux)] or UFH. Administration of LMWH, UFH or fondaparinux at thromboprophylactic doses for acutely ill hospitalized medical patients, in the absence of contraindication, is generally considered standard care. Main outcomes The primary composite outcome of ICU admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death at 28 days. Secondary outcomes include (evaluated up to day 28): 1. All-cause death 2. Composite of ICU admission or all-cause death 3. Composite of mechanical ventilation or all-cause death 4. Major bleeding as defined by the ISTH Scientific and Standardization Committee (ISTH-SSC) recommendation; 5. Red blood cell transfusion (>1 unit); 6. Transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipitate and/or fibrinogen concentrate; 7. Renal replacement therapy; 8. Hospital-free days alive; 9. ICU-free days alive; 10. Ventilator-free days alive; 11. Organ support-free days alive; 12. Venous thromboembolism (defined as symptomatic or incidental, suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); 13. Arterial thromboembolism (defined as suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); 14. Heparin induced thrombocytopenia; 15. Trajectories of COVID-19 disease-related coagulation and inflammatory biomarkers. Randomisation Randomisation will be stratified by site and age (>65 versus ≤65 years) using a 1:1 computer-generated random allocation sequence with variable block sizes. Randomization will occur within the first 5 days (i.e. 120 hours) of participant hospital admission. However, it is recommended that randomization occurs as early as possible after hospital admission. Central randomization using an interactive web response system will ensure allocation concealment. Blinding (masking) No blinding involved. This is an open-label trial. Numbers to be randomised (sample size) 462 patients (231 per group) are needed to detect a 15% risk difference, from 50% in the control group to 35% in the experimental group, with power of 90% at a two-sided alpha of 0.05. Trial Status Protocol Version Number 1.4. Recruitment began on May 11th, 2020. Recruitment is expected to be completed March 2022. Recruitment is ongoing. Trial registration ClinicalTrials.gov Identifier: NCT04362085 Date of Trial Registration: April 24, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

ABSTRACT Statistical process control has been widely used in agricultural operations for monitoring and improving process quality. This study aims to evaluate the Shewhart and exponentially weighted moving average (EWMA) control charts to monitor the performance of an agricultural tractor–planter set. The design is completely randomized based on the assumptions of statistical process control and comprises two treatments: day and night shift treatments. The data to assess the performance of the tractor–planter set are collected during the day and night shifts and used to evaluate the operating speed, motor rotation, engine oil pressure and water temperature, and hourly fuel consumption. The dataset comprised 40 samples compiled from the frontal monitor column inside a tractor cab. It is concluded that both Shewhart and MMEP/EWMA control charts can be used to evaluate engine performance based on the quality indicator parameters investigated, regardless of the normality assumption of the datasets.

Even with over 80% of the population being vaccinated against COVID-19, the disease continues to claim victims. Therefore, it is crucial to have a secure Computer-Aided Diagnostic system that can assist in identifying COVID-19 and determining the necessary level of care. This is especially important in the Intensive Care Unit to monitor disease progression or regression in the fight against this epidemic. To accomplish this, we merged public datasets from the literature to train lung and lesion segmentation models with five different distributions. We then trained eight CNN models for COVID-19 and Common-Acquired Pneumonia classification. If the examination was classified as COVID-19, we quantified the lesions and assessed the severity of the full CT scan. To validate the system, we used Resnetxt101 Unet++ and Mobilenet Unet for lung and lesion segmentation, respectively, achieving accuracy of 98.05%, F1-score of 98.70%, precision of 98.7%, recall of 98.7%, and specificity of 96.05%. This was accomplished in just 19.70 s per full CT scan, with external validation on the SPGC dataset. Finally, when classifying these detected lesions, we used Densenet201 and achieved accuracy of 90.47%, F1-score of 93.85%, precision of 88.42%, recall of 100.0%, and specificity of 65.07%. The results demonstrate that our pipeline can correctly detect and segment lesions due to COVID-19 and Common-Acquired Pneumonia in CT scans. It can differentiate these two classes from normal exams, indicating that our system is efficient and effective in identifying the disease and assessing the severity of the condition.

Understanding the sensitivity of a system's behavior with respect to parameter changes is essential for many applications. This sensitivity may be desired—for instance, in the brain, where a large repertoire of different dynamics, particularly different synchronization patterns, is crucial—or may be undesired—for instance, in power grids, where disruptions to synchronization may lead to blackouts. In this paper, we show that networks of coupled phase oscillators with nonlinear interactions can acquire a very large and complicated sensitivity to changes made in either their units' parameters or in their connections. Even modifications made to a parameter of a single unit can radically alter the global dynamics of the network in an unpredictable manner. This occurs over a wide parameter region, around the network's transitions to phase synchronization. We argue that this is a widespread phenomenon that can be expected in real-world systems, extending even beyond networks of oscillators.

This paper presents a complete procedure on prototyping using the FPGA of the STEMlab board and is intended to serve as a guide for developers, students and researchers interested in speeding up their projects and experiments. Due to the reconfigurability of its internal circuitry, being as simple as a code modification (using hardware description language), FPGA technology allows testing of several controller topologies and/or parameters without the need of any physical change at hardware. This feature allows a much faster development cycle of either commercial products or academic experiments. Besides the reconfigurability of the FPGA, the STEMlab board also offers the advantage of several peripheral already available, which includes, among others, high speed analog-to-digital and digital-to-analog converters, Ethernet communication and a dual-core ARM processor capable of running a Linux operating system. In this paper, a didactic method of use of this board is presented, from getting started to a complete academic and industrial application: detection of early damage on an induction motor using frequency response analysis.

This paper presents the detailed project of a modular educational kit to be used in research and teaching activities in the area of power electronics - with emphasis on applications in medium voltage multilevel converters. The half bridge topology has been chosen for the submodules, as they can be arranged together in a multitude of other topologies. A system composed by a mother board and daughter cards is presented. A DSP control card and a FPGA System-On-Module are inserted in the mother board in order to control the half bridge submodules. The targets of this project are applications in medium voltage - hence, the communication between the submodules and the FPGA/DSP is performed through optical fibers. Also a self power system is presented for the submodules, in order for them to operate at floating potentials. Experimental results have been presented for the most usual topologies of converters, including a Modular Multilevel Converter operating at 2000V.

ABSTRACT: Bovine tuberculosis (BTB) is a zoonosis caused by the bacterium Mycobacterium bovis, which induces the development of nodular and granulomatous lesions in various animal tissues. The recognition of these suggestive gross lesions during postmortem sanitary inspection in slaughterhouses provides a presumptive diagnosis, which requires the use of complementary tests to confirm the disease. This study aimed to verify the occurrence of BTB in cattle slaughtered in slaughterhouses in the state of Ceará, Brazil, using bacteriological and molecular methods. To this end, suggestive lesions were analyzed on carcasses condemned by the “Serviço de Inspeção Estadual” (SIE). The samples were submitted to microbiological analysis using culture media and specific staining followed by spoligotyping molecular technique for identification and genotyping of the mycobacteria. Occurrence of lesions suggestive of BTB was verified in bovine carcasses (0.071%) from different municipalities of the state. These lesions were located mainly in the lung (95.12%), lymph nodes (58.53%), and liver (36.58%). Microbiological culture showed bacterial isolation (17.94%), with the growth of colonies showing morphological and tannic characteristics belonging to genus Mycobacterium spp. Genetic polymorphism analysis identified M. bovis in all isolates, which were discriminated into six spoligotypes (SB0121, SB0295, SB1064, SB0120, SB0870, and SB0852). These profiles have been described in Brazil and several areas of the world, except for profiles SB1064 and SB0852, which were described in the country for the first time. The results show that the association of the diagnostic methods used was the basis for the first study on identification of mycobacteria found in the state, which may provide a database for the epidemiological study of BTB in the state of Ceará.

Purpose To evaluate the bond strength between polymer-based copings and zirconia copings as positive control, cemented on implant-supported titanium bases with different adhesive cement systems. Moreover, to evaluate if airborne-particle abrasion of polymethylmetacrylate (PMMA) would enhance the bond strength. Methods Four groups of different materials were used to fabricate the copings, 30 in each group: airborne-particle abraded milled zirconia (TAZirconia, control group), milled PMMA (TPMMA), airborne-particle abraded milled PMMA (TAPMMA) and 3 D-printed micro filled hybrid resin (TAMFH). Each group of copings was cemented on titanium bases by three different adhesive cement systems, 10 each: Multilink Hybrid Abutment, Panavia V5, RelyX Ultimate. The specimens were stored dry at room temperature for 24 h, subjected to thermocycling for 5000 cycles followed by evaluating the bond strength by tensile strength test. Results TPMMA and TAPMMA cemented with Multilink Hybrid Abutment showed statistically significant lower bond strength in comparison to TAZirconia and TAMFH. No difference was observed between the latter two. TPMMA, TAPMMA and TAMFH had a statistically significant lower bond strength compared to the control group when cemented with Panavia V5. TPMMA and TAPMMA cemented with Rely X Ultimate showed statistically significant lower bond strength in comparison to the control group. Conclusion Almost all experimental groups, except 3 D-printed MFH, performed inferior than the positive control group where the highest bond strength was reported for the cementation of zirconia copings cemented with Panavia V5 or Rely X Ultimate. Airborne-particle abrasion did not improve the bond strength of the PMMA, except when Multilink Hybrid Abutment was used.

Abstract Background The Global Burden of Diseases (GBD) 2017 database permits an up-to-date evaluation of the frequency and burden of diabetes at the state level in Brazil and by type of diabetes. The objective of this report is to describe, using these updated GBD data, the current and projected future burden of diabetes and hyperglycemia in Brazil, as well as its variation over time and space. Methods We derived all estimates using the GBD 2016 and 2017 databases to characterize disease burden related to diabetes and hyperglycemia in Brazil, from 1990 to 2040, using standard GBD methodologies. Results The overall estimated prevalence of diabetes in Brazil in 2017 was 4.4% (95%UI 4.0–4.9%), with 4.0% of those with diabetes being identified as having type 1 disease. While the crude prevalence of type 1 disease has remained relatively stable from 1990, type 2 prevalence has increased 30% for males and 26% for females. In 2017, approximately 3.3% of all disability-adjusted life years lost were due to diabetes and 5.9% to hyperglycemia. Diabetes prevalence and mortality were highest in the Northeast region and growing fastest in the North, Northeast, and Center-West regions. Over this period, despite a slight decrease in age-standardized incidence of type 2 diabetes, crude overall burden due to hyperglycemia has increased 19%, with population aging being a main cause for this rise. Cardiovascular diseases, responsible for 38.3% of this burden in 1990, caused only 25.9% of it in 2017, with premature mortality attributed directly to diabetes causing 31.6% of the 2017 burden. Future projections suggest that the diabetes mortality burden will increase 144% by 2040, more than twice the expected increase in crude disease burden overall (54%). By 2040, diabetes is projected to be Brazil’s third leading cause of death and hyperglycemia its third leading risk factor, in terms of deaths. Conclusions The disease burden in Brazil attributable to diabetes and hyperglycemia, already large, is predicted by GBD estimates to more than double to 2040. Strong actions by the Ministry of Health are necessary to counterbalance the major deleterious effects of population aging.

Abstract Background The TNF signaling pathway is involved in the regulation of many cellular processes (such as apoptosis and cell proliferation). Previous reports indicated the effect of human TNF-α on metabolism, physiology, gene expression and protein phosphorylation of the human parasite Schistosoma mansoni and suggested that its TNF receptor was responsible for this response. The lack of an endogenous TNF ligand reinforced the idea of the use of an exogenous ligand, but also opens the possibility that the receptor actually binds a non-canonical ligand, as observed for NGFRs. Methods To obtain a more comprehensive view, we analyzed platyhelminth genomes deposited in the Wormbase ParaSite database to investigate the presence of TNF receptors and their respective ligands. Using different bioinformatics approaches, such as HMMer and BLAST search tools we identified and characterized the sequence of TNF receptors and ligand homologs. We also used bioinformatics resources for the identification of conserved protein domains and Bayesian inference for phylogenetic analysis. Results Our analyses indicate the presence of 31 TNF receptors in 30 platyhelminth species. All platyhelminths display a single TNF receptor, and all are structurally remarkably similar to NGFR. It suggests no events of duplication and diversification occurred in this phylum, with the exception of a single species-specific duplication. Interestingly, we also identified TNF ligand homologs in five species of free-living platyhelminths. Conclusions These results suggest that the TNF receptor from platyhelminths may be able to bind canonical TNF ligands, thus strengthening the idea that these receptors are able to bind human TNF-α. This also raises the hypothesis that an endogenous ligand was substituted by the host ligand in parasitic platyhelminths. Moreover, our analysis indicates that death domains (DD) may be present in the intracellular region of most platyhelminth TNF receptors, thus pointing to a previously unreported apoptotic action of such receptors in platyhelminths. Our data highlight the idea that host-parasite crosstalk using the TNF pathway may be widespread in parasitic platyhelminths to mediate apoptotic responses. This opens up a new hypothesis to uncover what might be an important component to understand platyhelminth infections.

Résumé Contexte L’hyperplasie bénigne de la prostate (HBP) est l’un des troubles de la reproduction les plus courants chez le chien et chez l’homme. Le finastéride, un inhibiteur synthétique de l’enzyme 5α-réductase, est largement utilisé comme traitement médical. Bien que le sperme puisse être affecté à la fois par l’HBP et par le traitement avec le finastéride, l’influence directe sur l’intégrité de l’ADN reste peu claire. Le but de cette étude était ainsi de vérifier l’effet direct de l’HBP et/ou du traitement par finastéride sur l’intégrité de l’ADN des spermatozoïdes de chien. Dans la présente étude, 20 chiens mâles ont été randomisés selon un plan factoriel en 2x2 à l’un des 4 groupes expérimentaux suivants : Groupe HBP (n=5), Groupe HBP-Finastéride (n=5), Groupe non-HBP traité par Finastéride (n=5), et Groupe non-HBP non traité (n=5). L’analyse Le sperme a été réalisée mensuellement pendant 60 jours (J0, J30 et J60) soit après le début du traitement par finastéride ou à partir du diagnostic de HBP. L’intégrité de l’ADN des spermatozoïdes a été analysée par l’évaluation de la susceptibilité à la fragmentation (coloration au bleu de toluidine ; détermination de la structure de la chromatine des spermatozoïdes - SCSA), par l’évaluation directe de la fragmentation de l’ADN des spermatozoïdes (détermination de la dispersion de la chromatine des spermatozoïdes - SCDA) et par l’évaluation de la protamination des spermatozoïdes (chromomycine A3). Résultats L’intégrité de l’ADN des spermatozoïdes n’a pas été affectée par le traitement par finastéride. Cependant, les chiens avec HBP ont une susceptibilité plus élevée à la dénaturation acide de l’ADN des spermatozoïdes (SCSA) par comparaison aux chiens ne présentant pas d’HBP, ainsi qu’un pourcentage plus bas de spermatozoïdes avec intégrité de l’ADN (coloration au bleu de toluidine). Conclusions L’hyperplasie bénigne de la prostate induit des altérations de l’ADN des spermatozoïdes, alors que le traitement par finastéride n’influence pas directement par lui-même l’intégrité de l’ADN des spermatozoïdes.

Owing to climate change, species’ geographical distribution may be extended, reduced or displaced in the future. Across species’ ranges, novel climate conditions may also expose species to thermal conditions for which they are not adapted. Migration toward more suitable climates will, however, only be possible if species are able to keep pace with climate change. Here, we analyze different metrics to predict the impacts of climate change on the distribution of Amazon primates. We found that this iconic group will be exposed to novel climate conditions in a large portion of their territories and most species might not be able to track their preferred environmental conditions, even when their range is forecasted to expand. Remaining future populations are expected to become fragmented and to occupy sub-optimal conditions at the periphery of their projected bioclimatic envelopes. Our results suggest that climate change may have unprecedented impacts on Amazon biodiversity, especially for species with low dispersal ability, such as primates. In addition to deforestation, hunting, and disease spread, climate change is likely to add up to conservation-defying feedbacks for Amazon primate populations’ fitness and resilience dynamics.

Approximately 140 snake species are known to occur in the Atlantic Forest with nearly half being endemic to this ecoregion. However, the Atlantic forest is one of the most threatened tropical ecoregions, with only 16% of its original area remaining as forest. This extensive habitat loss must have had a negative effect on its snake fauna. Indeed, 53% of the threatened snakes of Brazil occur in the Atlantic forest. Therefore, basic natural history information that can potentially contribute to the conservation of Atlantic forest snakes are urgently needed. Here the natural history of a snake assemblage at Etá Farm region, Sete Barras municipality, south-eastern Brazil is described, and a visual guide and an identification key provided that can be used by researchers and local people to identify snakes from this region. Most of the species found in the field use both open areas and forests, are primarily terrestrial, present diurnal activity, and include frogs in their diet. A higher number of enlarged follicles, eggs, and/or embryos were recorded during the warm and rainy season. Seventeen different types of defensive tactics were recorded in the species found in the field. This study provides useful information for understanding the structure of snake assemblages of the Atlantic Forest and is potentially useful for conservation assessments and for designing conservation plans.

Abstract Background Acute hypoxemic respiratory failure is one of the leading causes of intensive care unit admission and is associated with high mortality. Noninvasive oxygenation strategies such as high-flow nasal cannula, standard oxygen therapy, and noninvasive ventilation (delivered by either face mask or helmet interface) are widely available interventions applied in these patients. It remains unclear which of these interventions are more effective in decreasing rates of invasive mechanical ventilation and mortality. The primary objective of this network meta-analysis is to summarize the evidence and compare the effect of noninvasive oxygenation strategies on mortality and need for invasive mechanical ventilation in patients with acute hypoxemic respiratory failure. Methods We will search key databases for randomized controlled trials assessing the effect of noninvasive oxygenation strategies in adult patients with acute hypoxemic respiratory failure. We will exclude studies in which the primary focus is either acute exacerbations of chronic obstructive pulmonary disease or cardiogenic pulmonary edema. The primary outcome will be all-cause mortality (longest available up to 90 days). The secondary outcomes will be receipt of invasive mechanical ventilation (longest available up to 30 days). We will assess the risk of bias for each of the outcomes using the Cochrane Risk of Bias Tool. Bayesian network meta-analyses will be conducted to obtain pooled estimates of head-to-head comparisons. We will report pairwise and network meta-analysis treatment effect estimates as risk ratios and 95% credible intervals. Subgroup analyses will be conducted examining key populations including immunocompromised hosts. Sensitivity analyses will be conducted by excluding those studies with high risk of bias and different etiologies of acute respiratory failure. We will assess certainty in effect estimates using GRADE methodology. Discussion This study will help to guide clinical decision-making when caring for adult patients with acute hypoxemic respiratory failure and improve our understanding of the limitations of the available literature assessing noninvasive oxygenation strategies in acute hypoxemic respiratory failure. Systematic review registration PROSPERO CRD42019121755

Category: Bunion; Midfoot/Forefoot Introduction/Purpose: Lapidus procedure (LP) for hallux valgus (HV) requires an adequate control of first metatarsal (M1) sagittal alignment to avoid dorsiflexion. Otherwise, clinical and functional impairment, including transfer metatarsalgia may occur. This study aimed to evaluate the effects of pre- and postoperative measurements of M1 sagittal alignment on clinical and functional outcomes, and whether these variations would lead to transfer metatarsalgia or not. Methods: 29 patients (36 feet) with a mean follow-up of 20 months after LP were reviewed. Clinical and functional data were assessed with the VAS for pain, AOFAS, LEFS and SF-12. SF-12 comprises physical and mental health scales (PCS-12 and MCS-12, respectively). Transfer metatarsalgia diagnosis was based on the clinical exam. M1 sagittal alignment analysis was based on the first metatarsal declination angle (FMDA) and Meary Angle (MA). Decrease of FMDA means that the M1 dorsiflected (Figure 1). Intermetatarsal angle (IMA) and hallux valgus angle (HVA) were assessed. Radiographic, clinical and functional measurements were compared. Intraclass Correlation Coefficients (ICC) were calculated for FMDA and MA. Linear regression was used to assess the association of Δ-FMDA and Δ-MA with clinical and functional questionnaires. Based on that, we assessed our sample at different cut-off points to evaluate whether a given Δ-FMDA and/or Δ-MA measurement was significantly related to the Δ-Questionnaires. Results: Pre- and postoperative ICC of FMDA was 0.90 and 0.91 and MA was 0.94 and 0.88, respectively. FMDA showed significant variation after the LP, but MA did not. IMA and HVA improved significantly. Significant clinical and functional improvement were observed, except in MCS-12. No patient developed transfer metatarsalgia. A direct correlation was found between ΔFMDA with Δ-PCS-12 and Δ-LEFS (p=.028 and p=.02, respectively), meaning that excessive dorsiflexion of M1 as measured by FMDA led to a decrease in PCS-12 and LEFS. We found that at the cut-off point of quartile 50%, in which our sample was divided equally, patients with Δ-FMDA below 3.2 degrees of dorsiflexion had significantly improved results on Δ-PCS-12 compared to those with greater values (p=.029) (Figure 2). Conclusion: The present study showed that excessive dorsiflexion of M1 led to decreased outcome scores as measured by PCS- 12 and LEFS. It supports that M1 dorsiflexion should be avoided after the LP. However, slight dorsal deviation can occur and, even so, satisfactory outcomes can be obtained. Further prospective and comparative studies with larger populations are required to evaluate the effects of M1 inclination on clinical and functional outcomes.

Background. Tooth-supported fixed dental prosthesis (FDP) is one of the most reliable treatment options to replace missing teeth. The longevity of the treatment could, however, be affected by several general and local factors, especially bruxism. Objective. To investigate the influence of bruxism on the long-term survival of tooth-supported FDPs in bruxers compared to a matched group of nonbruxers, taking several clinical variables into account. Materials and Methods. The present retrospective cohort study was based on records of patients treated with 3–7-unit tooth-supported FDPs with a minimum follow-up time of 6 months after prosthesis delivery. The criteria for the diagnosis of “possible” and “probable” sleep or awake bruxism were used. A matched group of nonbruxers was selected on the basis of similarities in four factors, patients’ gender and age, number of prosthetic units of the FDPs, and follow-up time. The paired-samples t-test or Wilcoxon signed rank test were used to compared mean values between the two groups. Contingency tables of categorical data were analyzed by McNemar’s test. Results. The cohort group consisted of 62 noncantilevered FDPs in each group, followed up for a mean of 110.1 and 106.5 months (bruxers and nonbruxers, respectively). Tooth-supported FDPs in bruxers presented significantly higher failure rate than in nonbruxers (32.3% vs. 25.8%, respectively; p=0.001). Loss of retention and tooth loss were the main reasons for failures in both groups. For nonsmokers, the FDP failure rate was higher in nonbruxers. Technical and biological complications were significantly more prevalent in bruxers compared to nonbruxers. Conclusions. Bruxism is suggested to increase technical and biological complications and FDP failure.

Two-phase aqueous systems have replaced and simplified steps in extraction and purification processes, especially for biocompounds. Thus, this study evaluated the liquid-liquid equilibrium behavior of Pluronic L64 + water + sodium salts at pH 5.0, 7.5, and 10.0. Sodium sulfate demonstrated the greatest phase separation, followed by sodium citrate and sodium tartrate. Higher pH values resulted in larger biphasic regions. The polymer distribution coefficients increased with the addition of salt. As pH increased, there was a tendency for Pluronic L64 to migrate to the polymer-rich phase. The Gibbs energy of micellization between −11,000 and −25,000 kJ mol−1 indicated the spontaneity of the process micellization for all systems, showing lower values for the systems with sodium sulfate. This parameter was related to the anion speciation at each pH. Besides, the effects of water structuring around ions and ion-polymer interaction influenced the phase separation.

Abstract Background Pulmonary endothelial injury and microcirculatory thromboses likely contribute to hypoxemic respiratory failure, the most common cause of death, in patients with COVID‐19. Randomized controlled trials (RCTs) suggest differences in the effect of therapeutic heparin between moderately and severely ill patients with COVID‐19. We did a systematic review and meta‐analysis of RCTs to determine the effects of therapeutic heparin in hospitalized patients with COVID‐19. Methods We searched PubMed, Embase, Web of Science, medRxiv, and medical conference proceedings for RCTs comparing therapeutic heparin with usual care, excluding trials that used oral anticoagulation or intermediate doses of heparin in the experimental arm. Mantel‐Haenszel fixed‐effect meta‐analysis was used to combine odds ratios (ORs). Results and Conclusions There were 3 RCTs that compared therapeutic heparin to lower doses of heparin in 2854 moderately ill ward patients, and 3 RCTs in 1191 severely ill patients receiving critical care. In moderately ill patients, there was a nonsignificant reduction in all‐cause death (OR, 0.76; 95% CI, 0.57‐1.02), but significant reductions in the composite of death or invasive mechanical ventilation (OR, 0.77; 95% CI, 0.60 0.98), and death or any thrombotic event (OR, 0.58; 95% CI, 0.45‐0.77). Organ support‐free days alive (OR, 1.29; 95% CI, 1.07‐1.57) were significantly increased with therapeutic heparin. There was a nonsignificant increase in major bleeding. In severely ill patients, there was no evidence for benefit of therapeutic heparin, with significant treatment‐by‐subgroup interactions with illness severity for all‐cause death (P = .034). In conclusion, therapeutic heparin is beneficial in moderately ill patients but not in severely ill patients hospitalized with COVID‐19.

The original formulation of the firefighter problem defines a discrete-time process where a fire starts at a designated subset of the vertices of a graph G. At each subsequent discrete time unit, the fire propagates from each burnt vertex to all of its neighbors unless they are defended by a firefighter that can move between any pair of vertices in a single time unit. Once a vertex is burnt or defended, it remains in that state, and the process terminates when the fire can no longer spread. In this work, we present the moving firefighter problem, which is a generalization of the firefighter problem where the time it takes a firefighter to move from a vertex u to defend vertex v is determined by a function τ. This new formulation models situations such as a wildfire or a flood, where firefighters have to physically move from their current position to the location of an entity they intend to defend. It also incorporates the notion that entities modeled by the vertices are not necessarily instantaneously defended upon the arrival of a firefighter. We present a mixed-integer quadratically constrained program (MIQCP) for the optimization version of the moving firefighter problem that minimizes the number of burnt vertices for the case of general finite graphs, an arbitrary set F⊂V of vertices where the fire breaks out, a single firefighter, and metric time functions τ.