Afforestation; Soil ecoenzymatic C: N: P; Specific enzyme activities; Soil C and N contents.

We report a case of colonic metastasis due to pancreatic adenocarcinoma.

Histone is a scaffold protein that constitutes nucleosomes with DNA in the cell nucleus. When forming histone, hetero octamer is assisted by histone chaperone proteins. As a histone chaperone protein, the crystal structure of yeast nucleosome assembly protein (yNap1) has been determined. For yNap1, a nuclear export signal/sequence (NES) has been identified as a part of the long -helix. Experimental evidence via mutagenesis on budding yeast suggests the NES is necessary for transport out from the cell nucleus. However, the NES is masked by a region defined as an accessory domain (AD). In addition, the role of the AD in nuclear transport has not been elucidated yet. To address the role of the AD, we focused on phosphorylation in the AD because proteome experiments have identified multiple phosphorylation sites of yNap1. To computationally treat phosphorylation, we performed all-atom molecular dynamics (MD) simulations for a set of non-phosphorylated and phosphorylated yNap1 (Nap1-nonP and Nap1-P). As an analysis, we addressed how the NES is exposed to the protein surface by measuring its solvent-access surface area (SASA). As a result, there was a difference in the SASA distributions between both systems. Quantitatively, the median of the SASA distribution of Nap1-P was greater than that of Nap1-nonP, meaning that phosphorylation in the AD exposed to the NES, resulting in increasing its accessibility. In conclusion, yNap1 might modulate the accessibility of the NES by dislocating the AD through phosphorylation.

Peer-review and subject-matter editing is the backbone of scientific publishing. However, early career researchers (ECRs) are given few opportunities to participate in the editorial process beyond reviewing articles. Thus, a disconnect exists: science needs high-quality editorial talent to conduct, oversee, and improve the publishing process, yet we dedicate few resources to building editorial talent nor giving ECRs formal opportunities to influence the publishing landscape from within. Here, we describe a “two-way” fellowship model that gives ECRs a “seat” at the editorial table of a field-leading journal. We describe both the necessary framework and benefits that can stem from editorial fellowships for ECRs, editors, journals, and the scientific community.

Background: Children with cancer diagnosis are overall at a higher risk of thrombosis. For a newly diagnosed bland thrombus, patients are commonly started on anticoagulants to prevent further extension and embolization of the clot. In the rare instance that a pediatric patient has a tumor thrombus, the role of anticoagulation is less clear. Procedure/Methods: Patients under 21 years of age with a finding of tumor thrombus on imaging from 2010-2020 at Texas Children’s Hospital were identified and their medical records were reviewed. Results: A total of 50 patients were identified. Most thrombi were incidental findings at diagnosis; however, there were two patients who presented with pulmonary embolism (PE). Inferior Vena Cava extension was noted in 36% of the patients and 24% patients had an intracardiac tumor thrombus. Hepatoblastoma (26%) was the most common malignancy associated with tumor thrombus. Anticoagulation was initiated in 10 patients (20%). Only 2 of these 10 patients showed response to anticoagulation. However, 40% (4/10) patients in the anticoagulation cohort were noted to have bleeding complications (p <.05). Conclusion: Children with intravascular extension of solid tumors were not commonly started on anticoagulation at the time of diagnosis, irrespective of the extent of tumor thrombus. Furthermore, we observed a significant trend toward higher incidence of bleeding complications after initiation of anticoagulation. There is inadequate evidence at this time to support routine initiation of anticoagulation in pediatric patients with intravascular extension of solid tumors.

It has been a challenge in automated analysis of medical and chemical knowledge to extract represent quantitative structure–activity relationship (QSAR) using intelligent computing in drug discovery. One of many domain-specific bottlenecks in drug discovery is robust conformation search in three-dimensional (3D) space for flexible drug candidates. The process involves researchers and machines working together to achieve their own strengths for greater outcome. The present study has been developing a method for conformational sampling conformers in the class of 4-anilinoquinazoline derivatives for epidermal growth factor receptor (EGFR) tyrosine kinases inhibitors (TKIs). We use AG-1478 to demonstrate how the new intelligent computing method helps to quantum mechanically determine 22 target drug conformer clusters and their properties from conformational sampling, based on density functional theory (DFT) method, time-dependent (TD)-DFT in solvents and clustering analysis (CA). The UV-vis spectra of the preferred conformers agree well with earlier experimental measurements in which the conformer dependent UV-Vis spectral shift of AG-1478 can be as large as approximately 15 nm. We are further developing this method to study and design new 4-anilinoquinazoline derivatives of EGFR TKIs.

Coronavirus disease 2019 (COVID-19) has been tied to many complications such as hypercoagulability. It is more commonly seen in patients admitted to intensive care unit. Herein, we report a case of an end stage renal disease patient who developed recurrent arteriovenous graft thrombosis in the setting of COVID-19.

1 Conflicts of interestESC has received research support from DBV Technologies; has been a member of advisory boards for Pfizer, Pediapharm, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi Genzyme, Bausch Health, Avir Pharma; is a member of the healthcare advisory board for Food Allergy Canada; was an expert panel and coordinating committee member of the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Guidelines for Peanut Allergy Prevention; and was co-lead of the CSACI oral immunotherapy guidelines.SJ has been on speaker’s bureaus for Aralez, Novartis, Astra Zeneca, and Sanofi, and on the advisory board for Sanofi.MH has provided speaker services for Pfizer, Pediapharm, and has been part of an advisory board for ALK and provides privately funded OIT.VC has been a participant on advisory boards for Sanofi Genzyme, Bausch Health, and ALK, speaker services for Aralez Pharmaceuticals and CSL Behring.DM has provided consultation and speaker services for Pfizer, Aimmune, Kaleo, Merck, Covis and Pediapharm, and has been part of an advisory board for Pfizer and Bausch Health. He sits on the editorial board for the Journal of Food Allergy.EA Section Head of Anaphylaxis/Food Allergy for the Canadian Society of Allergy and Clinical Immunology; sits on steering committee for Canada’s National Food Allergy Action Plan; moderator/speaker fees from Novartis, GSK, Sanofi, AstraZeneca.LS NoneTW speaking engagements for Pfizer and Stallergenes Greer, Advisory Board member for ALK and Leo PharmaJP is the Section Head of Allied Health for the Canadian Society of Allergy and Clinical Immunology; and sits on the steering committee for Canada’s National Food Allergy Action Plan

A predictive model based on Fick’s second law for radial diffusion is proposed and validated for modeling the diffusion of fragrances. A pure component, two binary systems, and a ternary system were used for validation. The model combines the prediction model to represent the liquid phase non-idealities, using the UNIFAC group contribution method, with the Fickian radial diffusion approach. The experimental headspace concentrations were measured in a diffusion chamber using the solid-phase microextraction (SPME) technique and quantified using gas chromatography with a flame ionization detector (GC-FID). The numerical solutions were obtained along with an analytical model considering constant surface concentration. The odor intensities of the studied systems were calculated using Stevens’ power law and the strongest component model, respectively. The numerical simulation presented good adherence to the experimental gas concentration data. The proposed methodology is an efficient and validated tool to assess the radial diffusion of fragrance and volatile systems.

Centrifugal pumps are used in several industrial processes. It is common the operation of this equipment with gas-liquid mixtures, which is the case of the electrical submersible pumping artificial lift method used in the oil industry. The increase of free gas fraction inside the pump may lead to unstable operation and problems such as surging and gas locking phenomena to occur. In this study a drift-flux model is proposed for the gas-liquid flow subjected to centrifugal fields using the impeller as an example. The model is closed with experimental data of bubble diameter, displacements and velocities acquired via high-speed camera at several different rotational speeds and gas mass flow rates using water as the continuous medium. From the modeling and the forces balance in the bubbles, a quantitative criterion for the start point of surging and gas locking conditions was proposed.

Introduction: With improving mortality rates in pediatric acute respiratory distress syndrome (PARDS), functional outcomes in survivors are increasingly important. We aim to describe the change in functional status score (FSS) from baseline to discharge and to identify risk factors associated with poor functional outcomes. Methods: We examined clinical records of patients with PARDS admitted to our pediatric intensive care unit (PICU) from 2009 to 2016. Our primary outcome was acquired morbidity at PICU and hospital discharge (defined by an increase in FSS ≥3 points above baseline). We included severity of illness scores and severity of PARDS in our bivariate analysis for risk factors for acquired morbidity. Results: There were 181 patients with PARDS, of which 90 (49.7%) survived. Median pediatric index of mortality 2 score was 4.05 (1.22, 8.70) and 21 (26.6%) patients had severe PARDS. 59 (65.6%) and 14 (15.6%) patients had acquired morbidity at PICU and hospital discharge, respectively. Median baseline FSS was 6.00 (6.00, 6.25), which increased to 11.00 (8.75, 12.00) at PICU discharge before decreasing to 7.50 (6.00, 9.25) at hospital discharge. All patients had significantly higher median FSS score at both PICU and hospital discharge compared to baseline. Feeding and respiratory were the most affected domains. After adjusting for severity of illness, severity categories of PARDS was not a risk factor for acquired morbidity. Conclusion: Acquired morbidity in respiratory and feeding domains was common in PARDS survivors. Specific attention should be given to these two domains of functional outcomes in these children.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection usually causes no or mild coryzal symptoms in the paediatric population. In this letter, we describe a 21-month-old boy infected with SARS-CoV-2 who presented atypically with features compatible with croup. With the current Coronavirus Disease 2019 (COVID-19) pandemic, infection control measures need to be appropriately heightened and early diagnostic sampling for SARS-CoV-2 should be carried out even in symptomatology that is atypical of COVID-19.

SCN5A gene variants are associated with both Brugada syndrome and conduction disturbances, sometimes expressing an overlapping phenotype. Functional consequences of SCN5A variants assessed by patch clamp electrophysiology are particularly beneficial for a correct pathogenic classification and are related to disease penetrance and severity. Here, we identify a novel SCN5A loss of function variant, p.1449Y>H, which presented with high penetrance and complete left bundle branch block, totally masking the typical findings on the electrocardiogram. We highlight the possibility of this overlap combination that makes impossible an electrocardiographic diagnosis and, through a functional analysis, associate the p.1449Y>H variant to SCN5A pathogenicity.

Letter to the Editor

The Green Odorous Frog (Odorrana margaretae) around the Sichuan Basin of western China displays a ring-shaped distributional pattern and possesses multiple replicate contact zones between lineages at various levels of differentiation. To understand its unique speciation history and mechanisms, we obtained 1,540 SNPs from 29 populations and 227 individuals using ddRAD sequencing. Population structure analysis revealed three groups within the species: The West, the North & South, and the East groups. These groups were initially isolated at ~2.03 million years ago, and subsequent post-glacial expansion produced the current ring-shaped distribution around Sichuan Basin with three contact zones. Hybridization in those zones involved lineages with different levels of divergence and produced greatly different outcomes. Both the hybrid zones at southwest (S-W) and southeast (E-NS) of the Basin have extensive admixture and less barrier effect. Consequently, the southern region has the highest genetic diversity and becomes an ‘evolutionary melting pot’. In contrast, the hybrid zone at northwestern corner (N-W), which resembles the overlap zone between two expansion terminals of a ring species, has limited admixture with a narrow geographic cline, suggesting partial reproductive isolation between the northern and western populations. The three hybrid zones likely resemble three time points along a speciation continuum; while both E-NS and S-W hybrid zones are merging, the N-W zone may have passed the ‘tipping point’ and is destined for a complete reproductive isolation over time.

Over the last decade, increasing attention has been paid to the molecular adaptations used by organisms to cope with thermal stress. However, to date, few studies have focused on thermophilic species living in hot, arid climates. In this study, we explored molecular adaptations to heat stress in the thermophilic ant genus Cataglyphis, one of the world’s most thermotolerant animal taxa. We compared heat tolerance and gene expression patterns across six phylogenetically distant species that live in different habitats and experience different thermal regimes. We found that all six species had similar heat tolerance levels and critical thermal maxima. Furthermore, the transcriptome analyses revealed that, although the number of differentially expressed genes varied widely for the 6 species (from 54 to 1,118), many were also shared. Functional annotation of the differentially expressed and co-expressed genes then showed that the biological pathways involved in heat-shock responses were similar among species and were associated with four major processes: the regulation of transcriptional machinery and DNA metabolism; the preservation of proteome stability; the elimination of toxic residues; and the maintenance of cellular integrity. Overall, our results suggest that molecular responses to heat stress have been evolutionarily conserved in the ant genus Cataglyphis and that their versatility may help workers withstand temperatures close to their physiological limits.

BCR-NTRK2 fusion in a Pediatric Patient with Spinal GangliocytomaAvanti Gupte, M.D.1, Neena I. Marupudi, M.D.1,2, M.S. 1,Swati Mody, M.D.1,2, William Kupsky M.D.1,2, Hamza S. Gorsi, M.D., M.P.H.1,3

Objective: To estimate the association between chronic hypertension and perinatal mortality and evaluate the extent to which this risk is impacted by preterm delivery. Design: Cross-sectional analysis. Setting: US, 2015-2018. Population: Singleton births from 20-44 weeks’ gestation. Main outcomes and measures: We derived the risk of perinatal mortality in relation to chronic hypertension from fitting log-linear Poisson models with robust variance. Risk ratios (RR) and 95% confidence intervals (CI) were estimated after adjusting for confounders. The impact of misclassifications and unmeasured confounding biases were assessed. Causal mediation analysis was performed to quantify the impact of preterm delivery on the association. Results: Of the 15,090,678 singleton births, perinatal mortality was 22.5 per 1000 births in chronic hypertensive pregnancies compared to 8.2 per 1000 births in normotensive pregnancies (adjusted RR 2.05, 95% CI 2.00, 2.10). Corrections for exposure misclassification and unmeasured confounding biases substantially increased the risk estimate. Although, causal mediation analysis revealed that most of the effect of chronic hypertension on perinatal mortality was mediated through preterm delivery, the perinatal mortality rates were highest at early term, term, and late term gestations, suggesting that a planned early term delivery at 37-386/7 weeks may optimally balance risk in these pregnancies. Additionally, 87% (95% CI 84, 90) of perinatal deaths could be eliminated if preterm deliveries, as a result of chronic hypertension were prevented. Conclusions: Chronic hypertensive pregnancies are associated with increased risk for perinatal mortality. Planned early term delivery and targeting modifiable risk factors for chronic hypertension may reduce perinatal mortality rates.