Background : Primary immune regulatory disorders (PIRD) is a new term coined for a group of PID where autoimmune complications predominate. Herein we present a case series of 10 cases with lipopolysaccharide (LPS)-responsive and beige-like anchor protein (LRBA) deficiency who presented with multiple autoimmunities. Methods: 10 patients with molecular diagnosis of LRBA deficiency were included and their clinical data was evaluated. Results: The mean age of onset was 4.3 years. Male to female ratio was 7:3. 8/10 had 2 or more autoimmune disease with autoimmune cytopenia being the commonest. Other autoimmune diseases seen were autoimmune hepatitis, inflammatory bowel disease, enteropathy, diabetes melitis, thyroiditis, CNS vasculitis, dermatitis and alopecia areata. All patients had evidence of lymphoproliferation with generalized lymphadenopathy and/or hepatosplenomegaly. 5/10 had hypogammaglobinemia, 3/10 had low T cells, two of whom had CD4 lymphopenia. 4/10 had low B and NK cells. 2 had compound heterozygous and 8 had homozygous mutations in LRBA gene. The treatment was diverse and included corticosteroids, cyclosporine, azathioprine, cyclosporine, rituximab, sirolimus and abatacept. One child has undergone successful HSCT and currently doing well. Conclusion: Patients with LRBA deficiency present with a broad range of clinical manifestations. High index of suspicion for a monogenic cause for polyautoimmunity in early childhood can reduce time delay in diagnosis. With increasing availability of transplant facilities the outcome for these patients can be significantly better.

Background: Clinical informatics tools to integrate data from multiple sources have the potential to catalyze population health management of childhood cancer survivors at high risk for late heart failure through the implementation of previously validated risk calculators. Methods: The Oklahoma cohort (n=365) harnessed data elements from Passport for Care (PFC) and the Duke cohort (n=274) integrated cancer registry and electronic health record data, using standard query language, to automatically extract chemotherapy exposures for survivors <18 years old at diagnosis. The Childhood Cancer Survivor Study (CCSS) late cardiovascular risk calculator was implemented and risk groups for heart failure were compared to the Children’s Oncology Group (COG) Long-Term Follow-up Guidelines. Results: The Oklahoma and Duke cohorts both observed good overall concordance between the CCSS and COG risk groups for late heart failure with weighted Kappa statistics of 0.70 and 0.75, respectively. Low-risk groups showed excellent concordance (Kappa >0.9). Moderate and high-risk groups showed moderate concordance (Kappa 0.44-0.60 across both cohorts). In the Oklahoma cohort, adolescents at diagnosis were significantly less likely to receive guideline-adherent care for echocardiogram surveillance compared with survivors <13 years old at diagnosis (OR 0.22; 95% CI 0.10-0.49). Conclusions: Clinical informatics tools represent a feasible approach to leverage discrete data elements regarding key treatment exposures from PFC or the EHR to successfully implement previously validated late cardiovascular risk prediction models on a population health level. Real-world evidence on the concordance of CCSS, COG, and IGHG risk groups promises to refine current guidelines and identify inequities in guideline-adherent care.

Here, we report the use of a methylene blue oral rinse for the treatment of oral mucositis--associated pain. A child receiving chemotherapy for acute lymphoblastic leukemia had progressive decline in clinical condition from uncontrolled oral pain associated with mucositis. Conventional therapy was shown to be ineffective and eventually discontinued. The patient received a methylene oral rinse treatment, which provided good pain control and allowed him to recover successfully completing his chemotherapy. The use of the methylene blue oral rinse can be a safe, inexpensive, and effective treatment for mucositis-related oral pain in the pediatric cancer patient population.

This paper presents an intelligent communication mechanism and sharing resources between a Service Requesting Cloud Node (SRN) and a Service Providing Cloud Node (SPN). The proposed mechanism selects the most optimal SPN among all SPNs, deployed at TEIN (Trans Eurasia Information Network) in South Korea, Pakistan, and Malaysia. The proposed mechanism uses a Machine Learning model for selecting the most optimal SPN and HTTP tunneling with Observer Pattern API for communication. The data obtained using monitoring tools is used to train the machine learning models for selecting the most optimal node based on minimum Round-Trip Time (RTT). To this end, we utilize Extra Trees (ET), Ridge Classifier, and K-Nearest Neighbor (KNN) machine learning algorithms. The ET algorithm outperforms the other utilized algorithm with 94% accuracy. HTTP tunneling and Observer Pattern API can be used for communication between two Clouds where the Clouds support a different version of L2 tunnels, such as VXLAN or GENEVE. Access from an instance of a Cloud to the physical machine of another Cloud is provided by an HTTP tunnel using an HTTP bridge. The Observer Pattern of software engineering is implemented as an API on the target Cloud SPN to respond to the request on the HTTP bridge from the source Cloud. This way, for a specific service request, an optimal SPN is selected by ML, and communication is then established by HTTP tunneling and Observer Pattern API

Climate change and rapid urbanization have exacerbated the occurrence and impact of floods. It is essential to carry out a quantitative flood risk assessment and manage the flood risk before a disaster occurs. This article presents a combined riverine flood risk model to obtain the exceedance probability loss (EPL) curve and expected annual damage (EAD) under the current climate. This model includes a rapid flood model and a flood damage model. It aims to simulate the flood risk and evaluate the flood damage at 10-, 30-, 50-, 100-, and 200-year return period events. The results show that: (1) The total inundation areas will sharply increase when the flood return periods are over 30 years. (2) The EAD is 1,476 million dollars in the Jiulong River Basin (JRB). When the flood return period is over 30 years, the total damage increases sharply. (3) The flood risk in the lower reaches of the JRB is higher than in the upper reaches when the flood event is beyond a 20-year return period. (4) Industrial sector damage is the largest, followed by tertiary industry, transportation, construction, agriculture, and infrastructure. This study will provide actionable information for future flood risk management, and this combined model chain is also suitable for other similar river basins.

Objectives This systematic review provides an overview of the effect of malnutrition on the pharmacokinetics of chemotherapy in children with cancer. Methods PubMed, Embase and Cochrane were searched to identify eligible studies. Malnutrition was referred to as undernutrition, as defined by the World Health Organisation and the Gomez Criteria. Results Four studies with a total of 668 children with cancer were included and n=121 (18%) were malnourished. In vincristine, the differences in pharmacokinetic parameters were statistically significant where clearance rates were commonly lower and area under the curve was increased in malnourished children. Conclusion The results are suggestive for pharmacokinetic alterations of chemotherapy in malnourished children with cancer. However, the data is scarce, groups are small, and most studies have been performed in high-income countries. Pharmacokinetic research among (severely) malnourished children with cancer is needed in order to improve their outcome, directed by sub-group and ultimately individualized drug dosing.

Background: Aging of the liver was regarded as a successful adaptation or as a progressive disease state remains a matter of controversy. This study aims to approach the mature investigation to determine the mature effects of exercise training, resveratrol intake, and the combination on SAMP8 mice liver. Methods: Histological of 3- and 6-month-old SAMP8 mice were examined by H&E and Masson’s trichrome staining. Apoptosis cells were determined by TUNEL staining. Examine molecular protein of p-PI3K/PI3K, p-Akt/Akt, Bad, cytochrome c, Bcl 2, ERK1, IL-6, STAT3, MEK5, p-ERK5/ERK5, FGF2, and MMP2 by western blotting. Results: Results showed that the cross-sections of 6-month-old SAMP8 mice livers observed lower adipocytes, collagen, and apoptosis cells appeared after exercise training, resveratrol intake, and their combination than 3-month-old SAMP8 mice. Combination habitual exercise training and resveratrol intake in the 6-month-old SAMP8 mice liver has significant increases in p-PI3K/PI3K (p<0.001) and p-Akt/Akt (p<0.01) ratios compared to 3-month-old SAMP8 mice. Exercise training, resveratrol intake, and combined exercise training and resveratrol intake facilitated ERK1-Bcl2 increases, and Bad, Cytochrome c, IL-6-STAT3-MEK5-p-ERK5/ERK5 and FGF2-MMP2 decreases in the 6-month-old SAMP8, but not 3-month-old SAMP8 mice liver. Conclusion: Fortunately, habitual exercise training and resveratrol intake combination observed in the liver of mature SAMP8 mice at 6 months of age has an excellent good reversed age interaction function in mature SAMP8 mice liver.

The Gempylidae (snake mackerels) family, belonging to the order Perciformes, consists of about 24 species described in 16 genera primarily distributed in tropical, subtropical, and temperate areas worldwide. Despite substantial research on this family utilizing morphological and molecular approaches, taxonomy categorization in this group has remained puzzling for decades prompting the need for further investigation into the underlying evolutionary history among the gempylids using molecular tools. In this study, we characterized and compared eight complete mitochondrial genomes for five Gempylidae species [Neoepinnula minetomai, Neoepinnula orientalis, Rexea antefurcata, Rexea prometheoides, and Thyrsites atun] using Ion-Torrent sequencing. Using Bayesian Inference and Maximum-Likelihood tree search methods, we investigated the evolutionary relationships of seventeen Gempylidae species using mitogenome data. In addition, we estimate divergence times for extant gempylids. We identified two major clades that formed approximately 48.05 (35.89 – 52.04 mya) million years ago; Gempylidae 1 [Lepidocybium flavobrunneum, Ruvettus pretiosus, Neoepinnula minetomai, Neoepinnula orientalis, and Epinnula magistralis], and Gempylidae 2 [Thyrsites atun, Promethichthys prometheus, Nealotus tripes, Diplospinus multistriatus, Paradiplospinus antarcticus, Rexea antefurcata, Rexea nakamurai, Rexea prometheoides, Rexea solandri, Thyrsitoides marleyi, Gempylus serpens, and Nesiarchus nasutus]. The present study demonstrates the superior performance of complete mitogenome data compared to individual genes in phylogenetic reconstruction. In addition to Cytochrome c oxidase subunit 1, NADH dehydrogenase subunit 2, and Cytochrome b, which are frequently employed in phylogenetic investigations, NADH dehydrogenase subunit 5 provided adequate resolving power. Analyses of selection pressure revealed purifying selection is predominant in Gempylidae mitogenomes. By including T. atun individuals from different regions we demonstrate the potential for the application of mitogenomes in species phylogeography.

ACE2 receptor plays a vital role not only in the SARS-CoV-induced epidemic but also in some diseases. Studies have been carried out on the interactions of ACE2- SARS-CoV proteins. However, comprehensive research has not been conducted on ACE2 protein by using bioinformatic tools. The present study especially two places, G104 and L108 points, which are effective in protecting the structure of the ACE2 protein, play a critical role in the biological functioning of this protein, and play an essential role in determining the chemical-physical properties of this protein, and play a crucial role for ACE2 protein-SARS CoV surface glycoprotein, were determined. It was also found that the G104 and L108 regions were more prone to possible mutations or deletions than the other ACE2 protein regions. Moreover, it was determined that all possible mutations or deletions in these regions affect the chemical-physical properties, biological functions, and structure of the ACE2 protein. Having a negative GRAVY value, one transmembrane helix, a significant molecular weight, a long-estimated half-life as well as most having unstable are results of G104 and L108 points mutations or deletions. Finally, it was determined that LQQNGSSVLS, which belongs to the ACE2 protein, may play an active role in binding the spike protein of SARS-CoV. All possible docking scores and results were estimated. Based on the docking score, MD results are taken and It is seen that mutation at G104 and L108 may affect the spike-ACE2 interaction. It is thought that this study will bring a different perspective to ACE2 _SARS-CoV interaction and other diseases in which ACE2 plays an important role and will also be an essential resource for studies on ACE2 protein.

Background Immune cells are important for the development of schistosomiasis japonica and are also critical for the treatment of schistosomiasis. The immune cells in the peripheral blood help assess the immune state. The peripheral lymphocytes in schistosomiasis mansoni were well studied, however immune cells in patients with different stages of Schistosomiasis Japonica are not well analyzed. Here we performed a preliminary study to explore characteristics of peripheral lymphocyte subsets in patients with different stages of Schistosomiasis Japonica. Methods 135 patients with S. japonicum infection and 25 healthy volunteers were included in this study, including 84 patients with chronic S. japonicum infection and 51 patients with advanced S. japonicum infection. Flow cytometry analysis was performed to evaluate peripheral lymphocytes including T cells, B cells and NK cells. Blood routine and liver function test data were analyzed. Ultrasound examination was used to access liver fibrosis according to the World Health Organization standard about ultrasound in schistosomiasis. Results Demographic data analysis suggested there was no difference in age and gender in patients with S. japonicum infection and health control group. Liver function tests showed that patients with advanced schistosomiasis had a higher incidence of liver function abnormality and blood lipid than those with chronic schistosomiasis. Blood routine results reflected that hemoglobin, red blood cells, platelets, as well as lymphocytes in the advanced group were significantly less than that in the chronic group. Furthermore, flow cytometry analysis indicated that the percentage of CD4 +T cells was lower in the advanced group, but the percentage of CD19 +B cells was higher in the advanced group. In addition, the number of CD3 +T cells, CD3 +CD4 +T cells, CD3 +CD8 +T cells, and NK cells was less in the advanced group when compared with those in the chronic group. In addition, there was a correlation between the decrease in CD4 + T cells and more severe fibrosis on ultrasound images. Conclusion Our results indicated that the immune state in the peripheral is different in different stages of S. japonicum infection. Lymphocyte subset analysis have potential to facilitate differential diagnosis of different stages of schistosomiasis japonica and even to be a prognostic factor.

Organoids are three-dimensional cell aggregates with near-physiologic cell behaviors and can undergo long-term expansion in vitro. They are amenable to high-throughput drug screening processes, which renders them a viable preclinical model for drug development. The procedure of organoid-based high-throughput screening has been extensively employed to discover small molecule drugs, encompassing the steps of generating organoids, examining efficient drugs in organoid cultures, and data assessment. Compared to small molecules, peptides are more straightforward to synthesize, can be modified chemically, and demonstrate a high degree of target specificity and low cytotoxicity. Therefore, they have emerged as promising carriers to deliver drugs to disease-associated targets, and could be efficient therapeutic drugs for various diseases. To date, organoids have been used to evaluate the efficacy of certain peptide agents; however, no organoid-based high-throughput screening of peptide drugs has been reported. Given the advantages of peptide drugs, there is an urgent need to establish organoid-based peptide high-throughput screening platforms. In this review, we discuss the typical approach of screening small-molecular drugs with the use of organoid cultures, as well as provide an overview of the studies that have incorporated organoids in peptide research. Drawing on the knowledge gained from small molecular screens, we explore the difficulties and potential avenues for creating new platforms to identify peptide agents using organoid models.

This letter proposes an orthogonal decoupling method for co-frequency MIMO antennas with unbroken metal rim, operating in Wi-Fi 2.4GHz. The decoupling technique just requires two lumped elements between two ports.Two orthogonal surface currents and radiation pattern diversity are obtained. By adding a capacitive and an inductor, with insensitive of matching circuits, it is easy and significant to improve isolation with near 50dB for smart watch antennas. Moreover, forearm causes lower isolated frequency, and has a little effect on impedance matching with the radiation pattern orthogonal to the forearm.

Nobody had ever imagined that the virus found on the Wuhan fish market would spread worldwide within a few months. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the seventh member of the coronavirus family that infects humans. Going through the corona-lane, mankind has faced different virus variants, i.e., COVID-19, delta B.1.617.2, and Omicron B.1.1.529. The outbreak of COVID-19 created a shocking situation for not only the healthcare system, but also the post-COVID-19 world, which is witnessing huge damage in the field of environmental health, education, economy, industrial imbalance, hunger, indebtedness, crisis, etc. in most cases. Now, the wide level of vaccination throughout the world controls the number of cases, but by looking at the global scenario and the latest Chinese lockdown, it can be concluded that it will take time to become normal. The present article is an effort to present the COVID-19 journey, how the situation was, how it is, and how it may be. The perspective towards climate action and its impact on the United Nation’s Sustainable Development Goals of the United Nations have also been discussed.

The interfacial contacts between the electron transporting layers (ETLs) and the photoactive layers are crucial to device performance and stability for OSCs with inverted architecture. Herein, atomic layer deposition (ALD) fabricated ultrathin Al2O3 layers are applied to modify the ETLs/active blends (PM6:BTP-BO-4F) interfaces of OSCs, thus improving device performance. The ALD-Al2O3 thin layers on ZnO significantly improved its surface morphology, which led to the decreased work function of ZnO and reduced recombination losses in devices. The simultaneous increase in open-circuit voltage (), short-circuit current density () and fill factor (FF) were achieved for the OSCs incorporated with ALD-Al2O3 interlayers of a certain thickness, which produced a maximum PCE of 16.61%. Moreover, the ALD-Al2O3 interlayers had significantly enhanced device stability by suppressing degradation of the photoactive layers induced by the photocatalytic activity of ZnO and passivating surface defects of ZnO that may play the role of active sites for the adsorption of oxygen and moisture.

Distributed energy resources (DERs) provide flexible load restoration strategies, which can effectively enhance the resilience of active distribution systems (ADSs). Whereas, the widespread DERs in ADSs complicate the supply-demand relationship and make the system resilience difficult to access. Therefore, this paper proposes a simulation-based resilience assessment algorithm of ADSs considering the microgrid formation based on grid-edge DERs. Microgrid formation is used to depict the resilience gain of grid-edge DERs on ADSs. Specifically, a resilience assessment framework for ADSs is firstly proposed, where the uncertainty of component state and supply-demand is modelled based on probability statistics. Then the mixed integer linear programming is used to search for optimal load restoration strategies with microgrid formation. On this basis, a set of resilience indices are defined to quantitatively analyse the resilience of ADSs, and a resilience assessment algorithm with uncertainty scenario generation is proposed to obtain these indices. Furthermore, extensive numerical results based on a modified IEEE 123-bus feeder validate the effectiveness of our proposed method.

Background and Purpose: Myocardial infarction (MI) is the leading cause of mortality globally due in part to the limited ability of cardiomyocytes (CMs) to regenerate. Recently, we demonstrated that overexpression of 4 cell cycle factors, CDK1, CDK4, cyclin B1, and cyclin D1 (4F), induced cell division in ~20% of the post-mitotic CMs overexpressed 4F. The current study aims to identify a small molecule that augments 4F-induced CM cycle induction. Experimental Approach, Key Results: Screening of small molecules with a potential to augment 4F-induced cell-cycle induction in 60-day-old mature human induced pluripotent cardiomyocytes (hiPS-CMs) revealed N-(4,6-Dimethylpyridin-2-yl)-4-(pyridin-4-yl)piperazine-1-carbothioamide (NDPPC), which activates cell cycle progression in 4F-transduced hiPS-CMs. Autodock tool and Autodock vina computational methods showed that NDPPC has a potential interaction with the binding site at the human p38⍺ mitogen-activated protein kinase (p38⍺ MAP kinase), a critical negative regulator of the mammalian cell cycle. A p38⍺ MAP kinase activity assay showed that NDPPC inhibits its activity in a dose-dependent manner. Overexpression of p38⍺ MAP kinase in CMs inhibited 4F cell cycle induction, and treatment with NDPPC reversed the cell cycle inhibitory effect. Conclusion and Implications: NDPPC is a novel inhibitor for p38⍺ MAP kinase and is a promising drug to augment CM cell cycle response to the 4F. NDPPC could become an adjunct treatment with other cell cycle activators for heart failure treatment.

Nonlinear frequency responses are a common problem in radio frequency (RF) components. Specifically, in wireless communication systems, signals are often unequally amplified or attenuated across a specified frequency band. Common communications components such as filters, amplifiers, and mixers can lead to nonlinear frequency responses, which can cause errors in transmitting and receiving. This article outlines the design and demonstration of a static and dynamic finite impulse response (FIR) digital equalizer circuit. Using predistortion topology with a coupled feedback loop, the adaptive LMS algorithm was implemented. The FIR filter was simulated in MATLAB and Vivado and then implemented onto an Eclypse Z7 FPGA evaluation board with no timing errors. Simulations showed that the custom RTL module gave the same frequency response that was produced in MATLAB calculations. The filter was able to dynamically equalize the frequency responses of different nonlinear boards that were used as the devices under test (DUT). Measurements showed that the equalizer was able to compensate for system distortion from 0.2 to 0.8 Nyquist frequency. The phase response remained relatively linear across the band of interest, with a group delay flatness less than 10ns.

The U2 small nuclear RNA auxiliary factor1（U2AF1）belongs to the splicing factor SR family. This spliceosome involves in intron removal from messenger RNAs (mRNAs) and exon-exon binding. Nevertheless, the mutation of U2AF1 is associated with myelodysplastic syndrome (MDS), bone marrow cancer, and solid tumors, including lung cancer, pancreatic carcinoma, and other malignant tumors. Besides, the expression and mutation of U2AF1 will promote the occurrence or prognosis of relevant diseases. Hence, targeted therapies are required in the treatment of relevant diseases.Unfortunately, it remains unclear about the role of U2AF1 in different diseases. Therefore, we summarized the pathogenic mechanism of U2AF1 in different malignant diseases and related targeted agents.

In the Indian-origin Kashmir valley, apple trees are among the most popular plants. Thousands of tons of apples are exported from Kashmir every year, generating substantial revenue. Many diseases affect apple trees, which results in devastated apple yields and major losses for apple growers. Apple plants are mostly infected with diseases that originate in the leaves. In a country like India, where half of the population works in agriculture, prompt detection and prediction of such diseases is critical. Traditionally, apple plant diseases were diagnosed using laboratory assistance, which is time-consuming and labor-intensive. This study began with the construction of an expert-annotated dataset of apple diseases of suitable size, containing around 10000 high quality RGB images covering all of the main foliar diseases as well as their symptoms and signs. As a next step, we propose the development of a deep learning-based apple disease detection system that can be used to identify symptoms efficiently and accurately. Today, machine learning and deep learning allow us to reliably detect whether a plant is infected or not. This article introduces a framework for predicting Kashmiri apple plant diseases based on deep learning. Our model relies on Convolutional Neural Networks (CNNs) to extract and predict features. Testing samples through our framework yields state-of-the-art results in identifying apple plant diseases with 92 percent accuracy. Further, we present a novel dataset containing samples of Kashmiri apple plant leaves with three distinct diseases. A comparison was made between five deep learning algorithms: Faster R-CNN, Tiny-YOLO v2, YOLO v3, SSD 300, and EfficientDet-D0. The purpose of this was to demonstrate the efficacy of the method. As a result of the comparison, the recommended method outperformed the other five algorithms in terms of mAP (98.21%), 75.34 f/s detection speed, 14.48 MB model size, 13.27%, 18.53%, 16.19%, 5.17%, and 7.89%. Additionally, it meets real-time requirements. Furthermore, various lighting conditions and apple tree varieties were studied in order to identify apple blooms. Based on the information, it was demonstrated how robust the approach was against different varieties of apple trees and lighting patterns. This method demonstrated the efficacy of real-time apple bloom detection. Orchard yield estimates and apple blossom thinning robots may benefit from these findings.

Ethanol fermentations can be prematurely halted as Saccharomyces cerevisiae faces adverse conditions, such as acidic pH, presence of acetic acid, and supraoptimal temperatures. The knowledge on yeast responses to these conditions is essential to endowing a tolerant phenotype to another strain by targeted genetic manipulation. In this study, physiological, genomic, and transcriptomic analyses were conducted to obtain insights on molecular responses which could potentially render yeast tolerant towards thermoacidic conditions. To this end, we used thermotolerant TTY23, acid tolerant AT22, and thermo-acid tolerant TAT12 strains previously generated. The results showed an increase in thermoacidic profiles in the tolerant strains. The whole-genome sequence revealed the importance of genes related to: H +, iron, and glycerol transport (i.e. FRE1/2, JEN1, VMA2, VCX1, KHA1, AQY3, and ATO2); transcriptional regulation of stress responses to drugs, ROS and heat-shock (i.e. HSF1, SKN7, BAS1, HFI1, and WAR1); and adjustments of fermentative growth and stress responses by glucose signaling pathways (i.e., ACS1, GPA1/2, RAS2, IRA2 and REG1). At 30°C and pH 5.5, more than a thousand differentially expressed genes (DEGs) were identified in each strain. The integration of results from genomics and transcriptomics revealed that, as part of their adaptive responses, evolved yeast strains aimed to adjust their intracellular pH by H + and acetic acid transport; modify their metabolism and stress responses via glucose signaling pathways; control of cellular ATP pools by regulating translation and de novo synthesis of nucleotides; and direct the synthesis, folding and rescue of proteins throughout the heat-shock stress response. Furthermore, tolerant strains did not show growth trade off under optimal ancestral conditions. Moreover, the motifs analysis in mutated TFs suggested a significant association of SFP1, YRR1, BAS1, HFI1, HSF1, and SKN7 TFs with DEGs found in thermoacidic tolerant yeast strains. This study provides insights into the molecular elements associated with yeast tolerance to acidic pH, acetic acid, and supraoptimal temperatures; information that can be used in inverse metabolic engineering.

The liver is one of the main organs involved in the metabolism of xenobiotics and a key organ in toxicity studies. Prior to accessing the hepatocytes, xenobiotics pass through the hepatic sinusoid formed by liver sinusoidal endothelial cells (LSECs). The LSECs barrier regulates the kinetics and concentrations of the xenobiotics before their metabolic processing by the hepatocytes. To mimic this physiological situation, we developed an in vitro model reproducing an LSECs barrier in coculture with a hepatocyte biochip, using a fluidic platform. This technology made dynamic coculture and tissue crosstalk possible. SK-HEP-1 and HepG2/C3a cells were used as LSECs and as hepatocyte models, respectively. We confirmed the LSECs phenotype by measuring PECAM-1 and stabilin-2 expression levels and the barrier’s permeability/transport properties with various molecules. The tightness of the SK-HEP-1 barrier was enhanced in the dynamic coculture. The morphology, albumin secretion, and gene expression levels of markers of HepG2/C3a were not modified by coculture with the LSECs barrier. Using paracetamol, a well-known hepatotoxic drug, to study tissue crosstalk, there was a reduction in the expression levels of the LSECs markers stabilin-2 and PECAM-1, and a modification of those of CLEC4M and KDR. No HepG2/C3a toxicity was observed. The metabolisation of paracetamol by HepG2/C3a monocultures and cocultures was confirmed. Although primary cells are required to propose a fully relevant model, the present approach highlights the potential of our system for investigating xenobiotic metabolism and toxicity.

Pediatric intensive care admissions for severe acute asthma during the COVID-19 pandemicSomayeh Bazdar1, 2, 3*, Sarah van den Berg4, 5*, Niels W. Rutjes4, Lizan D. Bloemsma1, 2, 3, George S. Downward6, 7, Letty A. De Weger8, Suzanne W.J. Terheggen-Lagro3, Yolanda de Wit-van Wijck1, 2, 3, Anke H. Maitland van der Zee1, 2, 3,4, Berber Kapitein5Department of Pulmonary Medicine, Amsterdam UMC, Amsterdam, The NetherlandsAmsterdam Institute for Infection and Immunity, Amsterdam, The NetherlandsAmsterdam Public Health, Amsterdam, The NetherlandsDepartment of Pediatric Pulmonology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsPediatric Intensive Care Unit, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDepartment of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The NetherlandsJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The NetherlandsLeiden University Medical Center, Department of Pulmonology and Department of Public Health and Primary Care, Postbus 9600, 2300 RC Leiden, The Netherlands* Co-first author: Both Somayeh Bazdar and Sarah van den Berg are first authors and contributed equally.Running title : Severe acute asthma during COVID-19

This study aimed to look into the impact of educational practices on the reading and writing skills of learners, with a specific focus on the gaps and bonds in EFL learning while communication skills carried follow-ups. The study employed a mixed methodology, which embraced communication contexts placed in the teaching process, and self-perceptions of the participants in a multidimensional communication axis to collect data via surveys, observational forms and exploratory statistics. The results indicate that while there is a stable level of variation in terms of reading and writing achievement, there are setbacks in certain areas such as fill-in-the-blank questions in complex activities and sentence rewriting tasks. Additionally, the study found that providing students with picture clues can improve their performance. The study also suggests that blending both reading and writing skills in activities can lead to large linkages and improvements in performance.

A document by Tomas Takac. Click on the document to view its contents.