Background: Pediatric idiopathic interstitial pneumonia (IIP) is a rare disease with no established diagnostic or therapeutic guidelines. Hydroxychloroquine (HCQ) has no indication for this disease and is contraindicated in patients under 6 years of age. The aim of this study was to evaluate the diagnostic procedure, and efficacy and safety of IIP treatment in Japan. Methods: The Japanese Society of Pediatric Pulmonology (JSPP) implemented a registration system from April 2010 to March 2020. The enrollment criteria were posted on the JSPP website, and e-mail requests for enrollment from physicians were accepted. Questionnaires were sent to investigate symptoms, laboratory findings, treatment effects, and outcomes. Results: Thirty-four patients were collected in a 10-year period. The age at onset ranged from 0 to 8 years. Genetic testing was performed in 29 cases, and mutations were found in 17 cases. Lung biopsies were performed in 16 patients, with nonspecific interstitial pneumonia being the most common cause. Twenty-eight patients received HCQ, 27 of whom were under 6 years of age at the start of treatment. The duration of HCQ treatment ranged from 1 month to 13 years, with no reports of retinopathy. Eighteen patients showed a good course of treatment with monotherapy with either steroids, HCQ, or a combination of both. Lung transplantation was reported in three cases. Six patients had died. Conclusion: This study demonstrated that half of the IIP patients were diagnosed by genetic testing. HCQ was used safely, including in patients under 6 years of age, with attention being paid to hypoglycemia.

Background: Recently, heated humidified high flow nasal cannula (HFNC) has gained popularity, and is now considered as standard respiratory support for pediatric patients with acute respiratory distress. However, there is limited data concerning bedside parameters for prediction of HFNC failure in pediatric patients. Material and method: A prospective observational study was conducted in 1 month to 15 year old patients with acute respiratory distress that required high flow nasal cannula support. The setting of high flow nasal cannula, vital signs, clinical respiratory score and the outcome of treatment were recorded. Data were analyzed to determine the predictors of HFNC failure. Results: In total 82 children participated in the study; from which 16 children (19.5%) did not response to high flow treatment (failure group). Pneumonia was the main reason for intubation (62.5%). Predictors of high flow nasal cannula failure at 12 hours were: SF index ≤ 166 (sensitivity 87.8%, specificity 62.5%, AUC 0.75), pROX index < 132 (sensitivity 84.8%, specificity 68.7%, AUC 0.77), and clinical respiratory score ≥ 6 (sensitivity 87.5%, specificity 96.9%, AUC 0.92). Conclusion: The clinical respiratory score is the most accurate predictor of high flow nasal cannula failure in pediatric patients. A clinical respiratory score of more than 6, at 12 hours, is a helpful indicator for high flow nasal cannula failure. pROX index, and the newly modified parameters in this study are also good for prediction of high flow nasal cannula failure Keyword: High flow nasal cannula, predictors, acute respiratory distress children

Nitrogen enrichment affects and changes the community structure of terrestrial ecosystems. Recently, intransitivity competition networks have been widely considered to in maintaining coexistence and biodiversity. However, whether the structure and function of the species competition network changes under nitrogen enrichment remains unclear. In this paper, we applied the Apriori algorithm to find dominant species assemblies to simulate competition matrices. We found that (1) intransitive competition networks derived by a species-dominant assembly accounted for a relatively large proportion of the derived networks, and the species acting as mediators constituted a nested pattern; (2)Under N enrichment, the complexity of the networks varied from an intransitive network to a sub-competition structure, and transitive networks was a transition structure between these two structures; (3) the negative effect of N-enrichment on species network was counteracted by mowing and rainfall; and (4) increasing the number of loops enhances the diversity in a community, while high competition among species is a representation of an intransitive competition network.

We derived a Gauss-cosh model for autocorrelation functions in the Fourier transform space by adopting the mass accumulation principle of the Grassmann space to the amplitude-frequency instead of the mass-point. Based on the Gauss-cosh model in the Fourier transform space, our main Gauss-cos model for autocorrelation functions was suggested on time domain. The physical interpretation of the Gauss-cos model was provided too. The new Gauss-cos model may be better for the kernel learning, pattern recognition or the approximation of the autocorrelation function to solve the time-dependent problems. Numerical experiments validated that the Gauss-cos model was efficient to fit the autocorrelation function of the fertility rate. The first two major principal phases of the Gauss-cos model we found for the autocorrelation function of the fertility rate were caused by the public diffusion and the mother-daughter diffusion.

Drought conditions and Verticillium wilt disease are two main factors limit production by preventing cotton from reaching their genetically predetermined maximum yields. Here, we isolated GhMYB36, a gene encoding a R2R3-type MYB protein in Gossypium hirsutum, which is confer drought tolerance and Verticilium wilt resistance both in Arabidopsis and cotton. GhMYB36 was highly induced by PEG-simulated drought stress (PSDS) in cotton. GhMYB36-silenced cotton plants were more sensitive to drought stress and Verticillium wilt resistance. GhMYB36 overexpression transgenic Arabidopsis and cotton plants showed better drought tolerance and Verticillium wilt resistance compared to wild type. The agro-infiltration-based transient expression of fused GhMYB36-GFP in tobacco cells indicated that GhMYB36 was located in the cell nucleus. In addition, the analysis of RNA-seq data together with qRT-PCR validation indicated that GhMYB36 improve the expression level of PR1 in GhMYB36 transgenic Arabidopsis. Luciferase interaction assays showed GhMYB36 was likely bind to the promoters of PR1 to activate the expression of PR1 and the interaction was confirmed by Yeast one hybrid. Collectively, our results suggest that GhMYB36 functions as a R2R3-type MYB protein and is essential to the improvement of drought tolerance and Verticillium wilt resistance in Arabidopsis and cotton by enhancing the expression of PR1.

Purpose: The aim of this study was to investigate the mechanism of the polarization response of CGA on mouse bone marrow-derived macrophages (BMDMs) towards the M1 phenotype in an in vitro model and to verify whether JAK-STAT1 and NF-κB are involved in the CGA induced polarization response of M1 macrophages. Results: The purity of F4/80 in BMDMs was >90% as determined by flow cytometry, and CGA significantly promoted the expression of MCHⅡ，CD80andCD86 molecules on the surface of BMDMs， upregulated the expression of M1 macrophage marker CCR7 (C-C chemokine receptor type7) (P < 0.05) and decreased the expression of M2 macrophage marker CD206. The expression of TNF-α, IL-6 and IL-12 mRNA was significantly increased in CGA treated BMDMs compared to the control group，while the expression of CD206，Chil3，IL-10 and Arg1 mRNA was significantly decreased (P < 0.05). 6 and IL-12 in BMDMs (P < 0.05)； In an in vitro bacterial phagocytosis and killing assay， CGA increased the uptake of FITC-Dextran by BMDMs and decreased the number of bacterial survival in Escherichia coli and Staphylococcus aureus；In addition, iNOS， NF -κBp65 and JAK-STAT1 protein expression levels were significantly increased in BMDMs (P < 0.05). These data suggest that CGA for M1 phenotypic polarization and expression of associated cytokines is closely associated with activation of NF-κBp65 and JAK-STAT1. Conclusion: CGA induces polarization of BMDMs towards M1-type macrophages and inhibits the trend towards M2-type macrophages，which is regulated by mediating JAK-STAT1 and NF-κB signalin

The impact of left bundle branch block (LBBB) after transcatheter aortic valve implantation (TAVI) on cardiac function remains uncertain. Its pathophysiology resembles a predominant electrical problem rather than myocardial damage. We present a case of deep prosthetic implantation, accompanied by LBBB in whom early treatment with CRT produced a striking improvement in cardiac function, preventing the development of real LBBB-induced cardiomyophathy.

Objective: To evaluate the association of COVID-19 status in pregnant women and hypertensive disorders of pregnancy. Design: Retrospective Cohort Study Setting: Multicenter study from a large metropolitan hospital system Population: Pregnant patients who tested positive for COVID-19 Methods: Patients who tested positive for COVID-19 during their pregnancy and delivered (index cases) were compared to the three subsequent deliveries of patients who tested negative (controls) at the same institution. We evaluated the impact of COVID-19 on the development of hypertensive disorders of pregnancy. We also evaluated the association of these disorders with maternal characteristics; demographics; prior pregnancy complications; current pregnancy complications; COVID-19 severity; laboratory values and inflammatory markers; and maternal and fetal outcomes. Univariable analysis was conducted with Student’s t-test, the chi-squared test and analysis of variance. Multivariable analyses were done using linear and logistic regression models. Main Outcome Measures: The incidence of hypertensive disorders of pregnancy in SARs-CoV-2 positive patients compared to SARs-CoV-2 negative patients. Results: Compared with pregnancies negative for SARs-CoV-2 infection, maternal SARs-CoV-2 infection was associated with an increased risk for hypertensive disorders of pregnancy (OR 3.68, 95% CI 1.67 -8.10). Overall rates of preeclampsia with severe features were significantly higher in patients with a COVID-19 diagnosis (18.6% vs 7.1%, p=0.006). An early SARS-CoV-2 infection (prior to 32 week’s gestation) conferred a higher risk of hypertensive disorders in pregnancy compared to SARs-CoV-2 infections diagnosed after 32 weeks’ gestation(OR=6.29, CI 1.64-24.07; p=0.007). Conclusion: COVID-19 is a risk factor for hypertensive disorders of pregnancy. Funding: None Conflicts of Interest: None

Letter to the Editor:The Rise of WNT-Activated Medulloblastoma?Submitted by:Andrew Walter, MS, MDAssociate Professor of PediatricsSidney Kimmel Medical College at Thomas Jefferson UniversityPediatric Hematology/Oncology and Neuro-oncologyDirector, Fellowship Training Program in Pediatric Hematology/OncologyA. I. duPont Hospital for Children1600 Rockland RoadWilmington, DE  19899phone 302-651-5500fax 302-651-5510andrew.walter@nemours.orgSage Taylor Green, DOCorresponding AuthorPediatric Hematology/OncologyA.I. duPont Hospital for Children1600 Rockland RoadWilmington, DE  19899phone 302-803-2324fax 302-651-5510sage.green@nemours.orgLetter to the Editor word count: 275

Introduction: Sickle cell anemia (SCA) is a disease that develops episodes of acute pain and multiple organ dysfunction that can affect the GH/IGF-1 axis. The severity of SCA is influenced by modifying factors, such as levels of fetal hemoglobin (HbF), the co-inheritance of alpha-thalassemia, or treatment with hydroxyurea (HU). Objective: To evaluate in children with SCA, the association of modifying factors with growth and serum levels of IGF-1 and IGFBP-3. Methods: This cross-sectional study in children with SCA evaluated bone age (BA), adult height prediction (AHP) using BA, a target height (TH) calculated as the mean SDS of the parents, and laboratory parameters. Children were grouped according to serum levels of HbF, co-inheritance of alpha-thalassemia, and HU therapy. Results and Conclusions: The mean age of the 39 patients was 8.2±2.2 years old. The average height was -0.75±0.30 SDS, and 10.3% (4/39) had short stature. Adjusted levels of IGF-1 or IGFBP-3 were significantly higher in children with SCA under HU therapy for more than 1 year, in children with HbF levels >10%, and in those without alpha-thalassemia. Using SDS, the growth potential of children with SCA in relation to their parents, calculated by the difference between AHP and TH, as well as the difference between children’s height and their TH, were lower in children with co-inheritance of alpha-thalassemia. Therefore, the co-inheritance of alpha-thalassemia in children with SCA may represent an additional cause for impaired growth.

Several mesoporous alkylated poly(ionic liquid)s (PILs) were synthesized precisely with divinylbenzene (DVB) and alkyl-functionalized ionic liquids (IL) through free radical copolymerization. After served as support for Candida antarctica lipase B (CalB) with a immobilized efficiency of 99%, this biocatalyst was further demonstrated highly advantageous for biodiesel production under mild conditions. Typical catalyst CalB0.2@PIL-C8 was capable of effectively converting soybean oil into biodiesel with a yield of 68.2%, which is higher than Novozym 435. And the biodiesel yield was almost 1.5 folds compared to that of free CalB under the same conditions. The recovery test and leaching test further confirmed its stability. The hydrophobic PILs not only provide suitable reaction micro-environment but also utilize the flexible hydrophobic alkyl chains to keep a conformation with more open active sites of lipase. This work discloses a promising strategy towards activating and stabilizing lipase dominated by hydrophobicity and surface potential regulation of support in heterogeneous enzymatic catalysis.

Inflammatory myofibroblastic tumor (IMT) is a rare cancer that is most commonly found in children and young adults, and it is usually detected in the lungs and abdomen. IMT is often associated with an anaplastic lymphoma kinase (ALK) gene rearrangement. We report the case of a 17-year-old male with ALK positive intracranial IMT managed with surgical resection and entrectinib, an ALK inhibitor. This case shows the importance of gene sequencing in diagnosing central nervous system (CNS) tumors and the promising role of ALK inhibitors in IMT treatment. Hypersensitivity to alectinib resulting in successful substitution to entrectinib was also noteworthy.

A document by Silvana Annamaria Urru. Click on the document to view its contents.

Objectives Our study aimed to compare the efficacy and toxicity of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) alone in patients with locally advanced hypopharyngeal squamous cell carcinoma (HPSCC). Design: Cohort Retrospective study Settings: Data of HPSCC patients collected from 2008 to 2020 Participants: 83 HPSCC patients Main outcomes measures: 83 patients with HPSCC in our center, who received IC followed by either CCRT or RT alone according to multidisciplinary team (MDT) discussion, were eligible for analysis. Among these patients, 52 patients underwent CCRT and 31 received RT alone after IC and we compared the two groups. Then we further compared the IC + CCRT and IC+RT groups in IC responders showing complete response (CR) and partial response (PR). Survival, toxicities clinical efficacy and outcomes were analyzed. Results For IC responders, IC+CCRT compared to IC+RT improved the locoregional relapse-free survival (LRPFS) (median: 39.3 vs.15.13 months; P=0.033), distant metastasis-free survival (DMFS) (median: 21.37 vs. 13.6 months; P=0.044), PFS (median: 27.87 vs.11.37 months; P=0.048) and the overall survival (OS) (median: 39.33 vs. 18.03 months, P=0.027). A multivariate analysis confirmed IC+CCRT was a positive prognostic factor for LRPFS and OS. However, for either all patients or IC non-responders, IC+CCRT did not improve the survival compared to IC+RT. Regarding acute toxicity, toxicities except ≥2 leucopenia were not statistically different between the two groups. Conclusion In the IC responders, CCRT may possess the survival benefit compared to RT alone in patients with HPSCC. Moreover, the toxicities of two groups were comparable during the therapy. Keywords hypopharyngeal carcinoma, induction chemotherapy, chemoradiotherapy, radiotherapy, survival

BACKGROUND: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. RESULTS: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFN production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract. CONCLUSIONS: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes.

Background: HAE patients have been postulated to be at increased risk for COVID-19 infection due to inherent dysregulation of the plasma kallikrein-kinin system. Only limited data has been available to explore this hypothesis. The aim of this study was to assess the interrelationship(s) between COVID-19 and HAE. Methods: Self-reported COVID-19 infection, complications, morbidity and mortality were surveyed using an online questionnaire. Subjects included HAE with C1 inhibitor deficiency (HAE-C1INH), normal C1 inhibitor (HAE-nl-C1INH and household controls. The impact of HAE medications was examined. Results: 1445 participants completed the survey, including: 695 HAE-C1INH, 175 HAE-nl-C1INH, and 292 controls. The incidence of reported COVID-19 was not significantly different between controls (9%) and HAE-C1INH (11%) but was greater in HAE-nl-C1INH (19%, p=0.006). Obesity was positively correlated with COVID-19 across the overall population (16% vs 10%, p=0.012), with a similar but non-significant trend in HAE-C1INH (14% vs 9%). Co-morbid autoimmune disease was a risk factor for COVID-19 in HAE-C1INH (p = 0.047). COVID-19 severity and complications were similar in all groups. Reported COVID-19 was reduced in HAE-C1INH subjects receiving prophylactic subcutaneous C1INH (5.6%, p=0.0371) or on-demand icatibant (7.8%, p=0.0016). HAE-C1INH subjects not on any HAE medications had an increased risk of COVID-19 compared to normal controls (24.5%, p=0.006). Conclusions: HAE-C1INH subjects not taking HAE medications had an enhanced risk for COVID-19 infection. Subcutaneous C1INH and icatibant significantly reduced this risk. The results implicate roles for the complement cascade as well as non-contact system related kinin generating pathways in the pathogenesis of COVID-19 in HAE-C1INH.

Medicinal and aromatic plants (MAPs), a subcomponent of Non-Timber Forest Products (NTFPs), are one of the important sources which supply the rural population with cash income. Nepal’s unique topography and varying climates have resulted in floral species count of 11,971, accounting for 3.2% of the world’s total flora. Department of Plant Resources (DPR) reported an increase in medicinal plant species from 700 to 819, with 285 endemic plant species from 43 families and 238 plant species chemically tested for medicinal significance. MAPs can be found at elevations ranging from 100 to 5500 m. The highest MAPs species richness was reported in the middle gradient. Despite having low plant diversity, the commercial values of the NTFPs found in Nepal’s mountains are the highest. The government of Nepal has prioritized 30 different MAP species for economic development, 12 species for cultivation and research, and imposed restrictions on the export of 12 species. Mid-Western and Far-Western development regions of Nepal account for more than 85% of total herbs collection in Nepal. About 80% of the population in Nepal depends upon MAPs for their primary health care needs. Around 100 Nepalese NTFPs are traded, but only 20 species account for 80% of the total trade in terms of volume and value. Nepal is ranked 42nd on the list, with $7.4 million in MAP exports, and 62nd on the list, with $3.3 million in essential oil exports. The overall contribution of NTFPs to national GDP was estimated to be 5%. In order to ensure food safety, reducing poverty, and improving livelihood, the promotion and domestication of NTFPs, proper harvesting mechanisms, and improved processing techniques are crucial.

Introduction Despite prioritization, routine antenatal influenza vaccine coverage is <16% in South Africa. We aimed to describe maternal influenza vaccine coverage in 27 antenatal clinics (ANCs) in Gauteng and Western Cape (WC) Provinces, where in collaboration with the Department of Health (DoH), we augmented the annual influenza vaccination programme among pregnant women. Methods From 2015 through 2018, 40 230 additional doses of influenza vaccine were added to the available stock and administered as part of routine antenatal care. Educational talks were given daily and data were collected on women attending ANCs. We compared characteristics of vaccinated and unvaccinated women using multivariable logistic regression. Results We screened 62 979 pregnant women during the period when Southern Hemisphere influenza vaccines were available (27 068 in Gauteng and 35 911 in WC). Vaccine coverage at the targeted clinics was 78.7% (49 355/62 682), although pregnant women in WC were more likely to be vaccinated compared to those in the Gauteng (Odds ratio (OR) =3.7 p<0.001). Women aged 25—29 and >35 years were less likely to be vaccinated than women aged 18—24 years (OR=0.9 p=0.053; OR=0.9 p<0.001). HIV positive status was not associated with vaccination (OR=1.0 p=0.266). Reasons for not vaccinating included: vaccine stock-outs where ANCs depleted available stock of vaccines and/or were awaiting delivery of vaccines (54.6%, 6949/12 723), refusal/indecision (25.8%, 3 285), and current illness that contraindicated vaccination (19.6%, 2 489). Conclusion Antenatal vaccination uptake was likely improved by the increased vaccine supply and vaccine education offered during our campaign.

In an modern world, image encryption played an vital role to prevent our data from illegal abuser entre. Based on this, in this paper the Markovian jump neural networks for synchronization of sampled-data control systems with two additive delay components are used on the looped functional method and its direct application is applied in image encryption. On the basis of generalized Lyapunov functional approach involves the states information such as x(tk) and x(tk+1) with few slack variables and a tuning parameter are introduced . Furthermore, the sampled-data controller is designed to contain both the present and delayed state information, thereby enhancing the control performance and design flexibility. Finally by using the new technique, the several examples are highlighted in the numerical section and also the effectiveness of an image encryption is studied.

In this article, generalized Kudryashov technique has been implemented to construct new soliton solutions of cubic KdV Boussinesq equation. Also, the OHAM has been employed to compute the numerical solution. The solutions thus acquired by the above methods are illustrated graphically. The techniques considered here are efficacious, plausible and can be employed in mathematical physics to compute new exact and numerical solutions of NPDEs.

Internal and external factors cause various types of wounds on the skin. Infections, nonhealing chronic wounds, and aesthetic and functional recovery all cause challenges for clinicians. The development of nanotechnology in biomedicine has brought many new materials, methods and therapeutic targets for the treatment of wounds, which are believed to have great prospects. In this work, the nanomaterials applied in different stages to promote wound healing and systematically expounded their mechanisms were reviewed. Then, the difficulties and defects of the present research and suggested methods for improvement were pointed out. Moreover, based on the current application status of nanomaterials in wound treatment, some new ideas for subsequent studies were proposed and the feasibility of intelligent healing by real-time monitoring, precision regulation, and signal transmission between electronic signals and human nerve signals in the future were discussed. This review will provide valuable directions and spark new thoughts for researchers.

The aim of this article is to analyze the impacts of Eckert, surface temperature and heat flux on two boundary layer flow of non-linear convection flow of micro-polar fluid past non-isothermal cylinder. The mathematical modeling for the flow problem has been created with suitable similarity transformation and dimensionless variable. The main nonlinear boundary value problems were reduced into mixed high order non-linear ordinary differential equations. The equations were solved using the method bvp4c from matlab software for numerous quantities of main constraints. The impacts of constraints on velocities, surface temperature and heat flux are examined and displayed through the graphs and tables. The convergence test has been maintained; for number of spots greater than apposite mesh number of spots, the precision is not affected. Moreover, a comparison with previous paper reachable in the literature has been reported and an excellent agreement is obtained. The acquiring shows that enhancing in the values of surface temperature and heat flux constraints (F, H) is to improve thermal diffusion that improve temperature distributions q(h);h(h).

A document by Zhen Chen. Click on the document to view its contents.

Although tyrosine kinase inhibitors have revolutionized treatment for chronic myeloid leukemia (CML), some patients exhibit drug resistance and poor clinical outcomes. Here, we explore the mechanistic aspects of cytotoxicity produced by thioridazine (TR). TR is an antipsychotic drug that has been investigated for its anticancer potential in a Philadelphia-positive human CML model. Our data show that TR selectively induced apoptosis in K562 cells compared with normal blood cells, which was mediated by Ca2+ and mitochondrial permeabilization. TR-induced cell death was accompanied by changes in Bcl-2 proteins and endoplasmic reticulum stress. TR also exhibited potent cytotoxicity against BCL-2/BCL-xL-overexpressing leukemia cells and presented an antitumor effect in vivo. These findings emphasize the high pharmacological potential of TR as an adjuvant in CML chemotherapy.