Background and Purpose Idiopathic pulmonary fibrosis is a progressive fatal disease characterized by interstitial remodeling, with high lethality and a lack of effective medical therapies. Tetrandrine has been proposed to present anti-fibrotic effects, but the efficacy and mechanisms of tetrandrine against lung fibrosis has not been systematically evaluated. We sought to study the potential therapeutic effects and mechanisms of tetrandrine in lung fibrosis. Experimental Approach The anti-fibrotic effects of tetrandrine were evaluated in bleomycin-induced mouse models and TGF-β1-stimulated murine lung fibroblasts. We performed Chromatin Immunoprecipitation (ChIP), Immunoprecipitation (IP) and mRFP-GFP-MAP1LC3B adenovirus construct to investigate the novel mechanisms of tetrandrine-induced autophagy. Key Results Tetrandrine decreased TGF-β1-induced expression of α-smooth muscle actin, fibronectin, vimentin and type 1 collagen and proliferation in fibroblasts. Tetrandrine restored TGF-β1-induced impaired autophagy, accompanied by the up-regulation and enhanced interaction of SQSTM1 and MAP1LC3-Ⅱ. ChIP studies revealed that NRF2 bound to SQSTM1 promoter in tetrandrine-induced autophagy. Furthermore, TGF-β1-induced phosphorylated mTOR was inhibited by tetrandrine, with reduced activation levels of Rheb. In vivo tetrandrine suppressed the bleomycin-induced expression of fibrotic markers and improved pulmonary function. Conclusion and Implications Our data suggest that tetrandrine might be recognized as a novel autophagy inducer, thus attenuating lung fibrosis. Tetrandrine should be investigated as a novel therapeutic strategy for IPF.

Studies on communities along large railroad infrastructures are very relevant because their operations can present socioeconomic and environmental impacts. This article examines the socioeconomic and environmental conditions of 32 communities directly affected by the Carajás Railroad, located in Pará and Maranhão states, eastern Amazon. The study analyses land-use changes in the territory and the indicators of those dimensions from 2010 to 2017. The environmental dimension involved qualitative analysis of satellite images from Google Earth, whereas the socioeconomic examined 17 variables collected during fieldwork in 2016 and 2017. To compare the indicators between urban and rural communities, the statistical tests of Kolmogorov Smirnov normality, the parametric Student’s t, and the non-parametric Mann-Whitney and Kruskal-Wallis were conducted, considering a 5% significance level. Overall, the results show urban communities are in better condition and that those on the Maranhão railroad side are in a less sustainable situation. The study also found that the community’s location along the railroad is associated with the forms of land-use and occupation in the territory; and directly influences the living conditions of locals since, in the communities near the railroad, there was a higher variation in land cover and socioeconomic indicators. The joint analysis of socioeconomic data with satellite images, in defined periods, can subsidize actions aimed at reducing risk situations and increasing the resilience and communities’ sustainability endeavors.

A 57-year female presented to emergency with features of right heart failure. On evaluation, she was found to have a large mass completely occupying right atrium and protruding into right ventricle through tricuspid valve. Here we present the 3D reconstruction images and intra-operative images of the RA mass.

Nel corso degli ultimi anni a causa dell’aumento delle attività antropiche è stato registrato un incremento delle emissioni di gas climalteranti (GHG) in atmosfera, principale causa dei cambiamenti climatici. In particolare nell’ultimo decennio è stata registrata una concentrazione media globale di anidride carbonica di 400 ppm, circa il 145% maggiore di quelle del periodo pre-industriale (prima del 1750). È necessario attuare dei protocolli e processi di minimizzazione delle emissioni di GHGs, al fine di rendere lo sviluppo industriale, e quindi antropico, più sostenibile. L’attività di ricerca svolta ha investigato l’implementazione e l’efficienza di rimozione della CO2 di un processo biologico innovativo denominato seedPBR, realizzato dal gruppo di Ingegneria Sanitaria Ambientale (SEED) del Dipartimento di Ingegneria Civile dell’Università degli Studi di Salerno. I risultati ottenuti durante l’attività sperimentale risultano essere promettenti: le efficienze di rimozione ottenute, sino al 82%, confermano il sistema seedPBR come tecnologia sostenibile ed efficiente per la mitigazione dei cambiamenti climatici.

Title PageManuscript TitleComment on: “A newborn with a large NTRK fusion positive infantile fibrosarcoma successfully treated with larotrectinib”Authors:Alana Slomovic, M.D., Pediatric Resident, Department of Pediatrics, Cohen Children’s Medical CenterTerry Amaral, M.D., Associate Chief - Division of Orthopedic Surgery, Long Island Jewish Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellIgor Lobko, M.D., Chief – Division of Vascular/ Interventional Radiology, Long Island Jewish Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellDavid Siegel, M.D., Executive Vice Chairman – Department of Radiology, Long Island Jewish Medical Center, Associate Professor, Zucker School of Medicine at Hofstra/ NorthwellRachelle Goldfisher, M.D., Division of Pediatric Radiology, Department of Pediatrics, Cohen Children’s Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellRachel Kessel, M.D., Division of Pediatric Hematology/Oncology, Department of Pediatrics, Cohen Children’s Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellCarolyn Fein Levy, M.D., Division of Pediatric Hematology/Oncology, Department of Pediatrics, Cohen Children’s Medical Center, Assistant Professor, Zucker School of Medicine at Hofstra/NorthwellCorresponding Author: Carolyn Fein Levy, M.D.269-01 76th Avenue, Suite 255New Hyde Park, NY 11040Phone: (718) 470 3460Fax: (718) 343 4642  email: clevy4@northwell.eduMain text word count: 564 wordsNumber of figures: 1Short running title: Infantile fibrosarcoma treated with larotrectinibKey Words: Infantile fibrosarcoma, Larotrectinib, NTRK fusionAbbreviations Key:

Catalytic efficiency and thermostability are the two most important characteristics of enzymes. However, it is always tough to improve both catalytic efficiency and thermostability of enzymes simultaneously. In the present study, a computational strategy with double-screening steps was proposed to simultaneously improve both catalysis efficiency and thermostability of enzymes; and a fungal α-L-rhamnosidase was used to validate the strategy. As the result, by molecular docking and sequence alignment analysis within the binding pocket, seven mutant candidates were predicted with better catalytic efficiency. By energy variety analysis, three among the seven mutant candidates were predict with better thermostability. The expression and characterization results showed the mutant D525N had significant improvements in both enzyme activity and thermostability. Molecular dynamics simulations indicated that the mutations located within the 5 Å range of the catalytic domain, which could improve RMSD, electrostatic, Van der Waal interaction and polar salvation values, and formed water bridge between the substrate and the enzyme. The study indicated that the computational strategy based on the binding energy, conservation degree and mutation energy analyses was effective to develop enzymes with better catalysis and thermostability, providing practical approach for developing industrial enzymes.

Medulloblastoma (MB) is the most common malignant brain tumor of childhood and is reported to have a low mutational burden. However, in this study, we identified nine MBs with high mutational burden by next generation sequencing. Of them, two had canonical mutations in the POLE proof-reading domain, where a large proportion of mutations in these tumor genomes contributed to signature 10. We report very rare incidences of hypermutation in MB and mechanisms driving mutagenesis. Strikingly, of the four known molecular subgroups in MB—-SHH, WNT, Group 3, and Group 4—both the POLE-mutated MBs belonged to the SHH subgroup.

Background: In pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the IKZF1 gene deletions is an molecular marker of poor prognosis. We aimed to assess the prognostic effect of different levels of IKZF1 gene deletions in pediatric BCP-ALL. Procedure: IKZF1 Δ2-8/ALB deletions were quantified using multiplex real-time quantitative PCR (RQ-PCR) in newly diagnosed pediatric BCP-ALL patients between June 2014 and January 2018. Seventy-four patients with IKZF1 deletions of ≥ 0.01% were included. Clinical characteristics, laboratory data, and treatment outcomes were analyzed. Results: The patients were divided into two groups: IKZF1 deletions of < 1% (Group A) and of ≥ 1% (Group B). Patients in group B had a higher BCR-ABL1 positive rate than those in group A (P = 0.001). The proportions of patients who had an age at onset of ≥10 years old, and white blood cell count ≥ 50×109/L were significantly higher in group B than in group A (P < 0.05). The 3-year overall survival (OS) and 3-year event-free survival (EFS) rates in group B were 79 ± 8.8% and 62.4 ± 9.7%, respectively, which were significantly lower than the 3-year OS (97.7 ± 2.2%, P = 0.022) and 3-year EFS (83.2 ± 5.8%, P = 0.019) in group A. Multivariate analysis revealed that the level of IKZF1 deletions of ≥ 1% and CNSL were independent risk factors of EFS. Conclusions: Pediatric BCP-ALL patients with high levels of IKZF1 gene deletions have a poorer prognosis than those with low levels.

Asparaginase, a critical component of current pediatric acute leukemia treatment protocols, is associated with a number of serious side effects, one of which is pancreatitis. Pancreatitis can result in significant morbidity and mortality from necrosis, pseudocyst formation, hemorrhage, systemic inflammation, intestinal perforation and sepsis. Another rare complication of pancreatitis is posterior reversible encephalopathy syndrome (PRES), likely mediated by systemic inflammation secondary to pancreatic autodigestion and pro-inflammatory cytokine-mediated vascular endothelial damage. Here we review this association in the literature and report two pediatric patients with leukemia who developed PRES secondary to asparaginase-associated pancreatitis.

Engaging Vulnerable Youth: An exploratory study on youth in Cottonera, youth work and STEAM engagement

Objectives Takayasu Arteritis (TA) is a rare non-specific vascular inflammation and has deleterious effects on patients’ health. Recent studies have advanced in TA diagnosis and treatment, but the research on the immune cell atlas of peripheral blood is still less. For this purpose, we performed single-cell RNA sequencing (scRNA-seq) to analyze the inflammatory cell types and cell markers in TA patients’ Peripheral blood mononuclear cells (PBMCs). Methods 4 TA patients and 4 health controls were enrolled in our study from 2019.10 to 2020.5. Their PBMCs samples were collected and performed scRNA-seq. We used Seurat package (v.3.2.2) in R studio (v.3.5.3) for data analysis, and 2 tests were applied for comparing the composition ratio of each cell type by SPSS 20.0. Results CD14+ monocytes, GZMB+ NKT cells, CD56dim CD16+ NK cells, and naive B cells were significantly increased in TA patients as compared to healthy controls and the expression of THBS1, CD163, AREG, IFITM1, TXNIP, and IGHGs was elevated in the peripheral blood of TA patients. Conclusion Except CD4+ T cells, monocytes, NK cells, NKT cells, B cells also play an important role in TA pathogenesis. The elevated markers have different functions in different types of PBMCs, and they can be used as potential diagnostic markers for TA diagnosis.

Introduction This study aims to compare the outcomes of minimally invasive coronary artery bypass grafting surgery (MICS CABG) versus median sternotomy (MS CABG) within an established minimally invasive cardiac surgical programme in Singapore. Methods We retrospectively analysed 111 propensity-score matched pairs of patients who underwent MICS CABG or MS CABG between January 2009 and February 2020 at the National University Heart Centre, Singapore. Minimally invasive direct coronary artery bypass (MIDCAB) patients were matched to single or double graft MS CABG patients (Group 1) while multivessel MICS patients were matched to MS CABG patients with the corresponding number of grafts (Group 2). Results 111 propensity matched pairs were obtained. The EuroSCORE II in the matched group cohorts were comparable (p=0.846). In both single and multivessel groups, MICS patients experienced shorter postoperative length of stay (p<0.001) and lower rates of prolonged ventilation (p=0.041) . Intraoperative transfusion rates and other postoperative outcomes were comparable between MICS and MS patients in the single and multivessel groups.mortality, reintervention heart failure rates were also comparable at 1 year follow up. In Group 1, no significant differences in procedural duration (p=0.574) and cardiopulmonary bypass duration (p=0.699) were noted. Moreover, MIDCAB patients had a smaller drop in postoperative haemoglobin levels (p<0.001). In Group 2, cardiopulmonary bypass (p=0.097) and length of procedure (p<0.001) were longer among multivessel MICS patients but did not translate to adverse postoperative events. Conclusion MICS CABG is a safe and effective approach for surgical revascularisation of coronary artery disease.

Beneficial mutations can become costly following an environmental change. Compensatory mutations can relieve these costs, while not affecting the selected function, so that the benefits are retained if the environment shifts back to be similar to the one in which the beneficial mutation was originally selected. Compensatory mutations have been extensively studied in the context of antibiotic resistance, responses to specific genetic perturbations and in the determination of interacting gene network components. Few studies have focused on the role of compensatory mutations during more general adaptation, especially as the result of selection in fluctuating environments where adaptations to different environment components may often involve tradeoffs. We examine if costs of a mutation in lacI, which deregulated expression of the lac operon in evolving populations of Escherichia coli bacteria, was compensated. This mutation occurred in multiple replicate populations selected in environments that fluctuated between growth on lactose, where the mutation was beneficial, and on glucose, where it was deleterious. We found that compensation for the cost of the lacI mutation was rare, but, when it did occur, it did not negatively affect the selected benefit. Compensation was not more likely to occur in a particular evolution environment. Compensation has the potential to remove pleiotropic costs of adaptation, but its rarity indicates that the circumstances to bring about the phenomenon may be peculiar to each individual or impeded by other selected mutations.

Human resource management has become an important part of enterprise management. How to select high-quality talents and how to allocate corresponding talents to appropriate works have become an increasingly acute problem. Traditional data cluster methods cannot effectively solve the above problem due to the high-dimensional data. Therefore, we propose a novel data cluster algorithm based on linear regression and residual analysis for Human Resource Management. Improved hybrid entropy weight attribute similarity is adopted for measuring the similarity between objects. The proposed local density calculation method based on KNN and Parzen window is used to calculate the density of each object. Then, we utilize the linear regression and residual analysis to select the clustering center points quickly and automatically, which can eliminates the subjectivity of artificial selection. A new clustering center objective optimization model is proposed to determine the real clustering center. Through theoretical analysis and comparative experiments on artificial data sets and real data sets, it shows that the proposed cluster algorithm can overcome the defects of the original algorithms, and achieve better clustering effect and lower computation time than state-of-the-art methods.

Deregulation of reduction-oxidation (redox) metabolism under environmental stresses results in enhanced production of intracellular reactive oxygen species (ROS), which ultimately leads to posttranslational modifications (PTMs) in structure and molecular function of responsive proteins. Redox PTMs are important mediators of cellular signalling and regulation and several proteomic approaches attempted to quantify them under various stresses in plants. We aimed to generate large-scale redox proteomics data in response to short-term salt stress in Brassica napus by analyzing reversible cysteine modification. We employed iodoTMT approach to analyze the redox proteome of Brassica napus seedlings under control and salt stress conditions. We identified 2,010 peptides in 1,017 proteins, of which 1,821 sites in 912 proteins had oxidative modification. The redox homeostasis of biology processes in chloroplast and cytoplasm were mainly affected and the modification levels of proteins involved in photosynthesis and glycolysis pathways were significantly changed. Two oxidatively modified proteins were selected from the candidates and their in vitro activity under oxidative stress was assayed and validated the findings of this proteomics study. This targeted approach should contribute to the understanding of redox-based molecular changes prevailing in Brassica napus proteome subjected to salt stress and the mechanism adopted to cope with it.

A 45-year-old man with bilateral blurred vision referred to toxicology department, after treatment he suffered from vision loss in left eye while his right eye was intact. Visual impairment due to methanol poisoning usually occurs bilaterally, but in our case was interestingly unilateral.

Snake bite is a common and very important issue threatening health worldwide. Patients who develop hemorrhagic or non-hemorrhagic blisters following snakebite, in addition to anti-venom, need broad-spectrum antibiotics and sometimes emergency surgical procedures and hospitalization to prevent serious complications such as necrotizing fasciitis, compartment syndrome.

We report the first incidental finding of congenital unilateral absence of the vas deferens and ipsilateral renal agenesis during endoscopic totally extraperitoneal inguinal hernia repair. The absence of the vasa deferentia occurs unilateral, associated with renal anomalies, or bilateral which has a genetic link to cystic fibrosis.

Mini Commentary: BJOG-20-1978.R1Title: Complement Receptors in Preeclampsia: Cleaning up Placental DebrisAuthor: Richard M. Burwick, MD, MPHAffiliation: Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA

Known knowns, unknown unknowns and everything in-between

As the fatigue life prediction of wire rope has the defects of large samples and many interference factors, this paper takes the 6×31WS+FC type wire rope as research carrier. Based on small samples, the grey particle filter method has been creatively proposed to realize the wire rope fatigue life prediction under various load conditions. First, combining the reliability life data prediction with the equivalent alternating stress of the dangerous part during the fatigue test, the reliability stress-life curve was determined. Subsequently, the particle filter method has been used to modify the curve to obtain the modified P-S-N curve. Finally, with theory of fatigue damage accumulation, the fatigue life prediction model was established, and compared with the test results. The results show that based on small sample conditions, the proposed method can predict the fatigue life of wire ropes under various loading conditions with high precision, which proves the general applicability.

Scale insects are hemimetabolous, showing “incomplete” metamorphosis and no true pupal stage. Ericerus pela, commonly known as the white wax scale insect (hereafter, WWS), is a wax-producing insect found in Asia and Europe. WWS displays dramatic sexual dimorphism, with notably different metamorphic fates in males and females. Males develop into winged adults, while females are neotenic and maintain a nymph-like appearance, which are flightless and remain stationary. Here we report the de novo assembly of the WWS genome with its size of 638.30 Mb (69.68Mb for scaffold N50) by PacBio sequencing and Hi-C. From these data, we constructed a robust phylogenetic analysis of 24,923 gene families from 16 representative insect genomes, which indicates that holometabola evolved from incomplete metamorphosis insects in the Late Carboniferous, about 50 million years earlier than previously thought. To study the distinct development of males and females, we analyzed the methylome landscape in either sex. Surprisingly, WWS displayed high levels of methylation (4.42% for males) when compared to other insects. We observed differential methylation patterns for genes involved in steroid and sesquiterpenoids production as well as related fatty acid metabolism pathways. We show here that both males and females exhibit distinct titer profiles for ecdysone, the principal insect steroid hormone, and juvenile hormone (a sesquiterpenoid), suggesting that these hormones are the primary drivers of sexually dimorphic features. Our results provide a comprehensive genomic and epigenomic resource of scale insects that provide new insights into the evolution of metamorphosis and sexual dimorphism in insects.

Objectives: evaluate the Surveillance Program of Gestational and Congenital Toxoplasmosis. Methods: 424 pregnant women were interviewed regarding their knowledge of prevention measures in 2019. Secondary prevention measures were assessed on the results of anti-Toxoplasma gondii serological tests were collected from pregnant women, from 2015 to 2018. the tertiary prevention measures, we screened the babies of mothers who had recent suspected infections of T. gondii to verify the referrals to the reference service. Results: 45.5% (192/424) reported that they had received guidance from health professionals; 35.4% (68/192) changed their risk habits. The variables of schooling and age, having received prior guidance from health professionals and feline possession, proved to be significant when associated with the notions of preventive measures. 90.2% (17,423 / 19,319) of pregnant women had undergone serological tests to detect anti-T. gondii antibodies but there was an excess in requests for tests and medication and only 40.6% (26/64) of the children were referred to the referral hospital. Conclusions: the Program presents positive results regarding the performance of serological screening in prenatal care; however, the dissemination of knowledge about the prevention of toxoplasmosis and the request for tests need to be improved.

Early improvement of smile esthetic is critical in patients with severely malformed front teeth particularly when it affects the patient's confidence. As illustrated in this report, correction of midline by moving a fused central incisor across the midpalatal suture was successfully performed to make an acceptable esthetic smile.