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Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation. Background HOPE-HF was a randomised, placebo-controlled, cross-over trial of AV-optimised His bundle pacing in patients with heart failure (LVEF ≤40%), a PR interval (≥200ms) and without left bundle branch block.1,2. In this analysis we studied the impact of baseline PR interval and acute blood pressure change at the optimal AV-delay on the placebo-controlled effect of His bundle pacing on the trial endpoints of peak VO2 (primary) and patient symptoms (using the Minnesota Living with Heart Failure Questionnaire). Methods and Results 167 patients were successfully implanted and randomised to 6 month blocks of pacing and placebo. We performed a non-invasive, high-precision protocol to calculate the optimal AV delay and associated acute blood-pressure response at randomisation. To test the impact of the baseline PR interval and acute BP response on the placebo-controlled effect of AV-optimised His bundle pacing on endpoints we compared Bayesian ordinal regression models and the relative explained variance (REV) of variables in the model. There was weak evidence that His-bundle pacing improved peak VO2 across all patients (OR 1.31, 95% CrI 0.86 to 2.01, Pr(OR > 1)=89%). The baseline PR interval had little impact on this benefit (REV 0%), and the blood pressure response was more likely (88% vs 12%) to be predictive. However, there was strong evidence that overall AV-optimised His-bundle pacing improved patient symptoms as compared to placebo (OR 1.58, 95% CrI 1.04 to 2.40, Pr(OR>1)=98%). Again, the baseline PR interval had little impact on this benefit (REV 0%) and the blood pressure response was much more likely (97% vs 3%) to be predictive. Higher acute BP increments led to greater placebo-controlled improvements in MLWHF at 6-months. Conclusion An individual’s acute BP response with AV-optimised His-pacing is a powerful predictor of their placebo-controlled improvement in symptoms (MLWHF) at 6-months. This can form the basis of patient selection for future studies and clinical practice.

Context: Distal femoral osteotomy (DFO) is a joint preservation procedure that corrects genu valgum deformities and patellofemoral maltracking, thereby restoring kinematics and unloading contact pressures in the lateral tibiofemoral and patellofemoral compartments. Objective: To evaluate the rates of return to work (RTW) and return to sport (RTS) after DFO for valgus malalignment and lateral compartment osteoarthritis through a systematic review of the literature. Data Sources: A systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted on the PubMed, Cochrane, and Embase databases. Study Selection: The search terms femoral osteotomy AND ( sports OR work) were used. Studies in which patients underwent concomitant total knee arthroplasty were excluded. Study Design: Systematic review. Level of Evidence: Level 4 (systematic review of level 4 studies). Data Extraction: Data included the number of patients, age, gender, laterality of operation, time to follow-up, rate of RTW and RTS, time to RTS, activity level on return, and activity level scores (Tegner, Marx, Lysholm, and the International Knee Documentation Committee). Risk of bias was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. Results: Seven articles with 194 patients were included. The average age ranged from 19 to 49 years with a mean postoperative follow-up range of 36 to 90 months. RTW data were available for 125 patients, of whom 42.1% to 91.3% returned by final follow-up. Data on RTS were available for 149 patients, of whom 70% to 100% returned at a range of 8.3 to 16.9 months postoperatively, and 41.6% to 100% returned to the same or greater level of sports activity. The Tegner and Marx activity level scores ranged from 3 to 4 and from 5 to 11, respectively, at final follow-up. Conclusion: Patients treated with DFO reported high rates of RTW and RTS, with most patients being able to return to recreational sport after surgery.

Purpose We present image classifiers based on Dense Convolutional Networks and transfer learning to classify chest X-ray images according to three labels: COVID-19, pneumonia, and normal. Methods We fine-tuned neural networks pretrained on ImageNet and applied a twice transfer learning approach, using NIH ChestX-ray14 dataset as an intermediate step. We also suggested a novelty called output neuron keeping, which changes the twice transfer learning technique. In order to clarify the modus operandi of the models, we used Layer-wise Relevance Propagation (LRP) to generate heatmaps. Results We were able to reach test accuracy of 100% on our test dataset. Twice transfer learning and output neuron keeping showed promising results improving performances, mainly in the beginning of the training process. Although LRP revealed that words on the X-rays can influence the networks’ predictions, we discovered this had only a very small effect on accuracy. Conclusion Although clinical studies and larger datasets are still needed to further ensure good generalization, the state-of-the-art performances we achieved show that, with the help of artificial intelligence, chest X-rays can become a cheap and accurate auxiliary method for COVID-19 diagnosis. Heatmaps generated by LRP improve the interpretability of the deep neural networks and indicate an analytical path for future research on diagnosis. Twice transfer learning with output neuron keeping improved DNN performance.

Neuromuscular disorders are often caused by heterogeneous mutations in large, structurally complex genes. Targeting compensatory modifier genes could be beneficial to improve disease phenotypes. Here we report a mutation-independent strategy to upregulate the expression of a disease-modifying gene associated with congenital muscular dystrophy type 1A (MDC1A) using the CRISPR activation system in mice. MDC1A is caused by mutations in LAMA2 that lead to nonfunctional laminin-α2, which compromises the stability of muscle fibres and the myelination of peripheral nerves. Transgenic overexpression of Lama1, which encodes a structurally similar protein called laminin-α1, ameliorates muscle wasting and paralysis in mouse models of MDC1A, demonstrating its importance as a compensatory modifier of the disease1. However, postnatal upregulation of Lama1 is hampered by its large size, which exceeds the packaging capacity of vehicles that are clinically relevant for gene therapy. We modulate expression of Lama1 in the dy2j/dy2j mouse model of MDC1A using an adeno-associated virus (AAV9) carrying a catalytically inactive Cas9 (dCas9), VP64 transactivators and single-guide RNAs that target the Lama1 promoter. When pre-symptomatic mice were treated, Lama1 was upregulated in skeletal muscles and peripheral nerves, which prevented muscle fibrosis and paralysis. However, for many disorders it is important to investigate the therapeutic window and reversibility of symptoms. In muscular dystrophies, it has been hypothesized that fibrotic changes in skeletal muscle are irreversible. However, we show that dystrophic features and disease progression were improved and reversed when the treatment was initiated in symptomatic dy2j/dy2j mice with apparent hindlimb paralysis and muscle fibrosis. Collectively, our data demonstrate the feasibility and therapeutic benefit of CRISPR-dCas9-mediated upregulation of Lama1, which may enable mutation-independent treatment for all patients with MDC1A. This approach has a broad applicability to a variety of disease-modifying genes and could serve as a therapeutic strategy for many inherited and acquired diseases.

Microplastics have been widely considered as contaminants for the environment and biota. Till now, most previous studies have focused on the identification and characterization of microplastics in freshwater, sea water, and the terrestrial environment. Although microplastics have been extensively detected in the wastewater, research in this area is still lacking and not thoroughly understood. To fill this knowledge gap, the current review article covers the analytical methods of microplastics originating from wastewater streams and describes their sources and occurrences in wastewater treatment plants (WWTPs). Studies indicated that microplastic pollution caused by domestic washing of synthetic fibers could be detected in the effluent; however, most microplastics from personal care and cosmetic products (PCCPs) can be efficiently removed during wastewater treatment. Moreover, various techniques for sampling and analyzing microplastics from wastewater systems are reviewed; while, the implementation of standardized protocols for microplastics is required. Finally, the fate of microplastics during wastewater treatments and the environmental contamination of effluent to environment are presented. Previous studies reported that the advanced wastewater treatment (e.g., membrane bioreactor) is needed for improving the removal efficiency of small-sized microplastics (

Microalgae have been widely considered as the potential sources for bio-fuel production without affecting the environment. Hydrothermal liquefaction (HTL) is a suitable technology for converting high water-containing feedstocks (e.g., microalgae) to liquid fuel. However, the structural diversity and rigidity of the microalgal cell wall remains as the major techno-economic bottlenecks for the recovery of intramolecular compounds (e.g., lipid) from microalgae. In this paper, the recent developments in cell disruption technologies and HTL for various microalgae strains are reviewed. The available literature investigating the effect of microalgal pre-treatment on the production of microalgae-derived bio-crude oil are presented. Furthermore, this article provides an extensive review of the recent studies on the HTL of microalgae, including the influences of feedstock characteristics and various operating conditions, underlying reaction mechanism, and physicochemical properties of liquefaction products.

This study evaluated the effects of high phytase doses and soybean meal (SBM) with different CP content on growth performance, ileal nutrient digestibility, digestible energy, plasmatic myo-inositol, phosphate release in vitro, and bone composition of broiler chickens. One thousand two hundred 1-day-old broilers were distributed in a 2 × 2 completely randomized factorial arrangement, with 2 phytase doses (1,000 and 2,500 phytase units [FYT]/kg of feed) and 2 SBM with different CP concentrations (45 and 47%), totaling 4 treatments with 12 replicates of 25 birds each. The chickens received feed and water ad libitum. Diets were based on corn and SBM, with different inclusions of soybean hull used to dilute the CP content of SBM according to each treatment. The inclusion of 2,500 FYT increased weight gain from 0 to 21 d (P

Objective: To propose novel SSVEP classification methodologies using deep neural networks (DNNs) and improve performances in single-channel and user-independent brain-computer interfaces (BCIs) with small data lengths. Approach: We propose the utilization of filter banks (creating sub-band components of the EEG signal) in conjunction with DNNs. In this context, we created three different models: a recurrent neural network (FBRNN) analyzing the time domain, a 2D convolutional neural network (FBCNN-2D) processing complex spectrum features and a 3D convolutional neural network (FBCNN-3D) analyzing complex spectrograms, which we introduce in this study as possible input for SSVEP classification. We tested our neural networks on three open datasets and conceived them so as not to require calibration from the final user, simulating a user-independent BCI. Results: The DNNs with the filter banks surpassed the accuracy of similar networks without this preprocessing step by considerable margins, and they outperformed common SSVEP classification methods (SVM and FBCCA) by even higher margins. Conclusion and significance: Filter banks allow different types of deep neural networks to more efficiently analyze the harmonic components of SSVEP. Complex spectrograms carry more information than complex spectrum features and the magnitude spectrum, allowing the FBCNN-3D to surpass the other CNNs. The performances obtained in the challenging classification problems indicates a strong potential for the construction of portable, economical, fast and low-latency BCIs., Comment: We included additional tests of statistical significance

This study was conducted to evaluate how the amount and type of diet consumed during the wean-to-estrus interval (WEI) affects reproductive performance and WEI duration in sows. A total of 542 sows were distributed into the following treatment groups based on a 2 × 2 factorial design: feed amount during WEI (2.75 or 3.75 kg/day) and diet (gestation [G] or lactation [L]) groups. Dietary treatments were as follows: high supply of G diet (GH), low supply of G diet (GL), high supply of L diet (LH), and low supply of L diet (LL). Sows were randomly allocated to groups according to their body score Caliper and birth order. There was an interaction (P < 0.05) between the factors for WEI duration, which was 0.2 days shorter in the GH and LL groups than in the other groups. No difference was observed between treatments (P>0.05) for the birth rate, total births, stillbirths, or total litter weight. There was a trend (P0,05) sobre a taxa de parto, total de nascidos, natimortos e peso total da leitegada. Houve uma tendência para maior taxa de nascidos vivos (P

Wastewater treatment is a high-cost and energy-intensive process not only due to large amounts of pollutants but also for the large volumes of water to be treated, which are mainly generated by human activities and different industries. In this regard, biological wastewater treatments have become substitutes to the current technologies, owing to the improved treatment efficiency and added value. Microbial fuel cells (MFCs) as one of the promising biological treatments have arisen as a viable solution for chemical oxygen demand (COD) removal and electricity generation simultaneously. Therefore, in this article, the effects of various operating conditions on the COD removal and power production from MFCs are thoroughly discussed. In addition, the advantages and weaknesses of current MFCs technologies used for different types of wastewater are summarized. Finally, the technical barriers facing by MFCs operation and the economic feasibility of using MFCs for wastewater treatment are provided.

Em muitos ingredientes utilizados na alimentação de perus, estão presentes compostos conhecidos como β-mananos, polissacarídeos não amiláceos que comprometem o aproveitamento dos nutrientes da dieta. O objetivo do presente experimento foi o de avaliar os efeitos da enzima β-mananase em dietas para peruas sobre a altura de vilos e a profundidade das criptas, aos 7 dias, e o desempenho zootécnico, aos 7, 14 e 21 dias de idade. Foram utilizadas 432 aves, distribuídas em delineamento experimental inteiramente ao acaso composto por 3 tratamentos: T1 – dieta basal; T2: dieta basal com redução de 150 kcal/kg e; T3: dieta basal com redução de 150 kcal/kg + adição da enzima β-mananase. Os dados obtidos foram submetidos à análise de variância e, no caso de diferenças significativas, comparadas estatisticamente pelo teste de Duncan (5%). A adição da enzima β-mananase permite reduzir os níveis de energia da dieta sem que sejam afetadas a altura de vilos e profundidade de criptas, aos 7 dias de idade, bem como o desempenho zootécnico das aves, aos 21 dias.

The objective of the study was to evaluate the deposition of selenium in the breast muscle of broilers fed different selenium sources during different periods. Two experiments were carried out with broilers fed 45% sodium selenite (SS) or 2% hydroxy-selenomethionine (HSM) to determine the selenium deposition rate in the muscle tissue. In Experiment 1, 48 broilers were distributed in a completely randomized design with six treatments with eight replicates each, consisting of diets containing 0 Se (0), 200 or 400 µgSS/kg (200 SS, 400 SS), or 100, 200, or 300 µgHSM/kg (100 HSM, 200 HSM, 300 HSM) for 10 days. The highest Se breast content was obtained with 300 HSM diet, followed by 200 SS diet compared to the other treatments. Experiment 2 had a completely randomized design following a plot scheme subdivided in time, and consisted of a basal diet supplemented with 300 µg SS/kg (300 SS), basal diet with 200 µg HSM/kg (200 HSM) or basal diet supplemented with 100 µgSS/kg and 100 µgHSM/kg (100 SS+100 HSM). Dietary Se sources did not influence Se breast content measured on days 3 and 6. However, on days 9 and 12, higher Se breast contents were measured in broilers fed 200 HSM and 100 SS+100 HSM diets compared with those fed 300 SS diet. In conclusion, the supplementation of broiler diets with HSM at 2% for a short period is more efficient to increase selenium deposition in the breast muscle than sodium selenite.

This study aimed to determine the most effective reaction medium for producing bio-crude oil from low-lipid microalgae via liquefaction treatment. To this end, the screening tests were carried out at 275 °C for 60 min by employing varying reaction media including water, water with four acid catalysts (formic acid, acetic acid, sulfuric acid, and hydrochloride acid), and four different organic solvents (methanol, ethanol, ethyl acetate, and acetone) without acid catalyst. In view of the bio-crude oil yield, methanol as the most effective reaction medium was choses for the further investigation on the effects of residence time, biomass/solvent mass ratio, and reaction temperature on the products distribution. The results showed that liquefaction at 225 °C for 60 min with a 1:5 biomass/solvent mass ratio led to the highest bio-crude oil yield of 85.5 wt% and a higher heating value (HHV) of 30.6 MJ/kg. Finally, a series of analytical approaches (elemental, GPC, TGA, GC–MS, and FT-IR analysis) were conducted for characterizing bio-crude oil.

An experiment was conducted to evaluate the growth performance, bone mineral composition, diet utilization, and plasmatic concentration of myo-inositol (MYO) in turkeys fed different phytase doses from 1 to 28 d. A total of three hundred and twenty 1-day-old turkeys were distributed in a completely randomized design with 4 treatments and 8 replicates of 10 birds each. Treatments included a basal diet without phytase; reduced diet (reduced -0.15% available P and -0.18% Ca) without phytase; reduced diet + 2,000 units of phytase (FYT)/kg; and reduced diet + 4,000 FYT/kg. From day 26 to 28, partial excreta collection was conducted, and on day 28, 7 birds per replicate were euthanized for collection of ileal content and left tibia bones were removed from 2 of the same euthanized birds. Feed, excreta, and ileal digesta samples were analyzed to determine nutrient digestibility and metabolizability, ileal digestible energy, and AME. Tibia bones were analyzed for ash, Ca, and P content, and calculation of Seedor index. On day 28, blood samples were collected from 2 turkeys per replicate to analyze plasmatic MYO concentration. Feed conversion ratio was not affected, but phytase supplementation resulted in higher feed intake and body weight gain compared to turkeys fed the reduced diet (P < 0.05), and both doses were similar to the basal diet. Increasing the phytase dose had a linear effect (P < 0.05) on ileal digestibility of P and metabolizability of DM, CP, Ca, and Na, and also on AME. P content in the tibia bone increased linearly (P < 0.05) with phytase supplementation, and the same linear increase (P < 0.05) was observed for plasmatic MYO. In conclusion, the supplementation of turkey poult's diets with high levels of phytase up to 4,000 FYT/kg improves diet utilization by increasing P digestibility and dietary metabolizability, leading to higher P content in the bone and enhancing MYO provision and absorption.

The supplementation of vitamin E on broiler chicken diets is essential to the prevention of lipid oxidation reactions in the meat and improvement of meat quality. The objective of this study was to assess the effect of different doses of dietary vitamin E on breast meat quality of broiler chickens in the finishing period. Five doses of vitamin E were used (30, 90, 150, 210, and 270 mg/kg feed) in broilers' diets from 42 to 54 d of age. A completely randomized design was conducted, followed by a split-plot, where the vitamin E dose was considered as the whole plot, and broilers’ age at slaughter was the subplot. Breast meat quality was assessed at 4 different ages (45, 48, 51, and 54 d old), using 50 birds per age, totaling 200 birds. Meat quality characteristics evaluated were: pH at 24 h post mortem, color (brightness, redness, and yellowness), water holding capacity, cooking loss, shear force, and lipid peroxidation. There was no interaction between age and dose of vitamin E for meat quality characteristics (P > 0.05). The age at slaughter had a quadratic effect (P

São inicialmente mostradas as idéias de grandeza e corpo clássicos, meio contínuo, funções temporal e constitutiva, densidade e taxa, sendo esta última relacionada a noções rudimentares sobre derivadas e funcionais. Em seguida, o conceito de propriedade é indicado, sem a utilização de expressões matemáticas, bem como a classificação das propriedades em intensivas, extensivas e extensivas aditivas. Complementarmente, os conceitos matemáticos de equação diferencial exata e inexata são discutidos e relacionados ao de propriedade. Nesta discussão, aparece o ilogismo e a inoportunidade inerentes ao uso de mais do que um único símbolo matemático para representar o diferencial de uma variável, uso este proveniente de um errôneo conceito de diferencial. O conceito exato é, então, brevemente referido.

Co-liquefaction of algal biomass (AB) and sawdust (SD) was investigated in ethanol-water mixed solvent for the production of bio-crude. Effects of temperature (200–300 °C), residence time (30–120 min), ethanol-water mixed solvent composition (0/100–100/0 wt/wt), and AB/SD mass ratio (0/100–100/0) on the products distribution were explored. The results indicated that both AB/SD and ethanol/water exhibited positive synergistic effects on the co-liquefaction process. The highest bio-crude yield of 58 wt% was obtained from co-liquefaction of AB and SD (50/50, wt/wt) in ethanol-water (75/25, wt/wt) mixed solvent at 250 °C for 60 min. In addition, the bio-crude produced from the mixed feedstocks contained a higher fraction of light oil components than that produced from only AB or SD. In addition, this work demonstrated the promise of recycling the aqueous by-product form the co-liquefaction process as a reaction medium for the process, aiming to reduce overall waste generation and increase the bio-crude quality.

GUS (β-glucuronidase) is a chemiluminescent reporter gene that has been used in E. coli, fungi, yeast, mammalian cells, plant cells and microalgae. Currently, the GUS gene fusion system used for detection of GUS enzyme activity is carried out by cell lysis and requires 500 μl cell lysate. Hence, GUS activity cannot be assessed by high throughput screening (HTS) method. This study addresses this by using a HTS technique to quickly isolate transgenic strains (shown using Chlorella vulgaris) expressing high GUS activity in a 96 well microplate format. In this technique, quantitative results were obtained without carrying out cell lysis and all the experiments were carried out in a 96 well microplate. The method developed is cost effective, less labor intensive and can be carried out in a timely manner. For this, a new GUS reporter vector pBIN + TetR + TetO was developed, followed by transformation (Agrobacterium tumefaciens), screening and characterization of the transgenic C. vulgaris. In the screening study, strain number 18 showed the highest fluorescence intensity (16,988 ± 1168). The GUS enzyme was found to be stable for >8 h for intact cell and lysed cell studies. The optimum concentration of Triton X-100 to release the product (4-Methylumbelliferone) into buffer was 0.1% and the fluorescence intensity was 28,397 ± 787. The values of Km and Vmax of the recombinant GUS for lysed cells were 0.1304 ± 0.0101 mM and 0.35 ± 0.004 pmol 4-MU/min/ml of crude cell lysate respectively.

Microalgae have been proposed as an alternative lutein source due to their high productivity, reliability, and versatility. In this study lutein and lipid extraction from wet Chlorella vulgaris UTEX 265 was investigated. The lutein production was monitored throughout the microalgal growth phase and several extraction parameters such as the sample size, drying method, and cell disruption method were investigated. The performance of solvents on lutein extraction was compared using Nile Red as a solvatochromic polarity probe. The simultaneous lutein and lipid extraction was also studied for different polarities using an ethanol-hexane binary solvent at the optimal solvent compositions suitable for lutein extraction. Among the solvents investigated, 3:1 (v/v) ethanol/hexane was recognized as the optimal solvent for lutein and lipid co-extraction, which contributed to a 13.03 mg g−1 lutein and 101.8 mg g−1 FAME yield. The saponifiable lipids content (86.9% w/w) was higher than conventional extraction methods. Based on our results, wet extraction approach exhibits good potential, while the bead-beater is the most suitable technique for cell disruption and lutein extraction.

Phyco-remediation is an environmental-friendly method, which involves the application of beneficial microalgae to treat wastewater-containing pollutants for a diverse range of conditions. Several industrial processes generate hyper saline wastewater, which is a significant challenge for conventional wastewater treatment, and the disposal of saline waters also has a negative impact on the environment. Road salt run-off is one such saline wastewater stream not currently treated and one that contributes significantly to negatively impacting receiving bodies of water. In this study, Nannochloropsis microalgae were able to assimilate95% of the nitrates within 8 days in road salt concentrations ranging from 2.6% to 4.4% under phototrophic cultivation mode. Biomass yields of 1-2 g/l of culture were obtained with the maximum lipid of 22% (g/g) biomass in the road salt media. The crude road salt media provided all the essential micronutrients needed for algal cultivation. The fatty acid composition analysis of the obtained lipid composed of C16 and C18 over 45% of FAME are suitable for biofuel. This study has established that the use of road salt containing nitrate and phosphate nutrients will support the growth of marine micro algae for remediation of a waste water system that are the concern at winter-prevalent regions.

In this study, a novel two-stage hydrothermal liquefaction (HTL) process was employed to produce low-nitrogen bio-crude oils from microalgae, involving pre-treatment of the microalgae with a pre-cooled NaOH/urea solution or a dilute acid and HTL of the pre-treated algal feedstock at 250°C for 10–50 min. The results indicated that the pre-treatment with a pre-cooled NaOH/urea solution effectively removed carbohydrates and protein from the raw microalgae, leading to a decrease in carbohydrates and protein content by 12 wt% and 10 wt% (both absolute values), respectively, while retaining 70 wt% of the solid mass, corresponding to as high as 82% carbohydrates removal efficiency and 40% protein removal efficiency. The two-stage HTL process slightly increased the overall bio-crude oil yields relative to the conventional single-stage HTL process, and the bio-crude oils obtained from the two–stage HTL process have a better quality than those obtained from the single-stage HTL, in terms of lower nitrogen and oxygen levels and higher energy content.