Sánchez-Tójar et al. (2020, Ecol Lett) question the methodology, transparency and conclusion of our study (Yin et al. 2019, Ecol Lett, 22, 1976). I feel that these arguments ignore critical assumptions and are based on a misunderstanding of our peer-review process. General does not mean always; the jury is in deciding when and where a transgenerational effect is beneficial, which enlightens future research.

Despite extensive research, the pathophysiology and prevention of pre-eclampsia remain elusive, diagnosis is challenging, and pre-eclampsia remains associated with adverse maternal and perinatal outcomes. Angiogenic biomarkers, including placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1), have been identified as valuable biomarkers for preterm pre-eclampsia, accelerating diagnosis and reducing maternal adverse outcomes by risk stratification, with enhanced surveillance for high-risk women. PlGF-based testing is increasingly being implemented into clinical practice in several countries. This review provides healthcare providers with an understanding of the evidence for PlGF-based testing and describes the practicalities and challenges to implementation.

Objective To investigate the association between antenatal depression and anxiety and early pregnancy Body Mass Index (BMI) within and between White British and South Asian women. Design Retrospective analysis Setting The Born in Bradford cohort, UK Population White British and South Asian pregnant women, 2007-2011 Methods Mother’s BMI was stratified into six World Health Organisation BMI categories (underweight, recommended, overweight or obese class 1-3). To determine associations with outcomes, univariate and multivariate logistic regression models (adjusting for maternal age, education, deprivation and smoking) were used. Main outcome measure Depression and anxiety using the General Health Questionnaire (GHQ); a GHQ score of >0 for the depression subscale and >6 for anxiety. Results There were 7824 women included (3514 White British and 4310 South Asian). South Asian women were significantly more likely to have depression than White British (43.3% vs 36.1% p<0.0001) and less likely to have anxiety (45.3% vs 48.4% p<0.01). There was no significant association between early pregnancy BMI and depression or anxiety in South Asian women. White British women with an overweight BMI had higher odds of anxiety compared with women with a recommended BMI (Adjusted Odds Ratio 1.25, 95% Confidence Interval 1.05-1.47). No significant associations were observed for other BMI categories. Conclusion Although South Asian women have a higher prevalence of depression than White women in this cohort, the known associations between maternal obesity and anxiety do not appear to be present. More studies are needed using validated depression tools for South Asian pregnant women.

Mini-commentary on BJOG-19-1677.R1: Risk-factors for second-line dactinomycin failure after methotrexate treatment for low-risk gestational trophoblastic neoplasia: a retrospective study

In the present paper initial problem for the integro-differential diffusion system with nonlocal nonlinear source is considered. The results on existence of local mild solution and nonexistence of global weak solution to the nonlinear integro-differential diffusion system are presented.

The purpose of this paper is to study the fluid-structure interaction (FSI) problem which is a simplified model to describe high frequency and small displacement oscillation of elastic structure in fluids. The elastic structure displacement is modeled by a fourth order nonlinear hyperbolic square equations, the motion of fluid is modeled by the time-dependent incompressible Navier-Stokes equations. we prove the existence of at least one weak solutions (global in time) to this problem by compactness method. The result both holds for two-dimensional and three-dimensional cases.

Background and Purpose The development of biased agonism provides a promising avenue to improve the pharmacological properties of fentanyl derivatives, but the molecular mechanism underlying ligand bias still remains ambiguous. Therefore, we sought to find out the critical sites of μ-receptor governing ligand bias and clarify corresponding molecular mechanism for designing and synthesizing effective analgesics with reduced adverse effects. Experimental Approach Critical sites governing ligand bias were identified both by computational prediction and cell assay-based bias analysis on wild-type and site-directed mutant μ-opioid receptor. Then molecular dynamics simulations of wild-type and mutant μ-opioid receptor were conducted to investigate the mechanism of bias activation. Key Results D3.32A and H6.52L mutation disrupted the binding of fentanyl derivatives with μ-opioid receptor. W6.48L mutation drove most fentanyl derivatives to β-arrestin-bias but promote sufentanil to cAMP signaling-bias. The result of molecular dynamics simulation showed that W6.48 and Y7.43 were paired activation switches of ligand bias at μ-opioid receptor. Conclusion and Implications D3.32 and H6.52 were critical residues in driving morphine and fentanyl derivatives to bind with μ-opioid receptor. W6.48 was a pivotal residue in governing the bias signaling and the interactions of ligands with W6.48 and Y7.43 were the structural determinants for the signaling bias of μ-opioid receptor, which will be conducive for better design and synthesis of effective opioid analgesics with the reduced adverse effects.

Purpose: This study was designed to investigate the effects of miR-24 and miR-27 on Th2 in children with non-atopic INS. Methods: Isolateing PBMCs by Ficoll density gradient, and transfected with human miR-24, miR-27 mimics/miR-24, miR-27 mimics control and miR-24, miR-27 inhibitors/miR-24, miR-27 inhibitor control. After that Real-time PCR to investigate the levels of microRNAs and IL-4mRNA, Flow cytometry to test the frequency of Th2 cells, and Cytometric bead array to measure the concentration of IgE, IL-4 and IL-13 in plasma. Results: The proportion of Th2 cells in peripheral blood of children with INS in the initial atopic and non-atopic groups were significantly higher (P<0.05), and there was no significant difference in the proportion of Th2 cells in the remission group (P>0.05). Plasma IgE, IL-4 and IL-13 were significantly increased in the initial atopic and non-atopic groups (P<0.05). MiR-24 and miR-27 were remarkably downregulated in the initial non-atopic group (P<0.05). The expressions of miR-24 and miR-27 were up-regulated in the initial non-atopic and control group, the proportion of Th2 cells and IL-4 mRNA expression were remarkably decreased (P<0.05), and the expressions of miR-24 and miR-27 were down-regulated, the proportion of Th2 cells and IL-4 mRNA expression were remarkably increased (P<0.05). Conclusion: There were high IgE in children with both atopic and non-atopic INS during the active period, which might be related to the high expression of IL-13 and IL-4 induced by the Th2 cells drifting. MiR-24 and miR-27 negative regulated the expressions of Th2 cells in INS.

Background and Purpose: Ningetinib is a tyrosine kinase inhibitor for the treatment of non-small cell lung cancer (NSCLC). When co-administered with gefitinib, the high plasma exposure of N-demethylated metabolite M1 was reduced by more than 80%, whereas it is surprising that of ningetinib was not clearly affected. The present study aims to investigate the drug interaction mechanism of ningetinib and gefitinib. Experimental Approach: NSCLC patients were recruited. Metabolic and transport mechanisms were investigated using in vitro models. Deuterated M1 (D6-M1) and mice were used to study the pharmacokinetic of M1. Key Results: In vitro experiments indicated that CYP1A1 was primarily responsible for M1 formation. Gefitinib was demonstrated to a strong inhibitor of CYP1A1 with Ki value of 0.095 μM. Co-administration of ningetinib increased blood exposure of intravenously administered D6-M1 by 75% in mice. M1 was identified as the substrate of the efflux transporters P-gp, BCRP and MRP2, while ningetinib was an inhibitor of these efflux transporters. Consequently, the high plasma exposure of M1 in patients was attributed to its low tissue affinity and the inhibitory effect of the parent drug on M1 canalicular efflux. Conclusion and Implications: When co-administered, gefitinib inhibited the formation of M1 and reduced its plasma exposure, but due to the low metabolic yield of M1 in vivo, the pharmacokinetics of the parent drug ningetinib was not influenced. Inhibition of the CYP1A1 may increase the target tissue concentration of ningetinib. The long-term safety profile and efficacy of ningetinib combined with gefitinib should be concerned in NSCLC patients.

After the well-known classification formulated by Crawford S. Holling in 1959 of the functional responses dependent only of the prey populations, various other have been proposed. In this work a simple Leslie-Gower type predator-prey model is analyzed, incorporating the Rosenzweig functional response described by $h\left( x\right) =qx^{\alpha }$, with $0<\alpha <1$. This function does not conform to the types proposed by Holling, since is not bounded. Although this functional response is non-differentiable for $x=0 $, it is proved that the obtained system is Lipschitzian. However, the existence of a separatrix curve $\Sigma $ in the phase plane it is proven, which divides the phase plane en two complemntary sectors. According to the relative position of the initial conditions respect to the curve $\Sigma $ , the trajectories can have differents $\omega $-$limit$, which can be the equilibrium $\left( 0,0\right) $, or else, a positive equilibrium point, or a limit cycle or a heteroclinic curve. These properties show the great diffference of this model with the original and well-known Leslie-Gower model (when $\alpha =1$), since this last has only a unique positive equilibrium, which is globally asymptotically stable. Then, it can concluded that i) a small change in the mathematical expression for the functional response, it produces a strong change on the dynamics of model. ii) \ a slightest deviation in the initial population sizes, respect to the curve $\Sigma $, it can signify the coexistence of populations or the extinction of both. Numerical simulations are given to endorse our analytical results.

An enhanced analytical technique for nonlinear oscillators having a harmonic restoring force is proposed. The approach is passed on the change of the auxiliary operator by another suitable one leads to obtain a periodic solution. The fundamental idea of the new approach is based on obtaining an alternative equation free of the harmonic restoring forces. This method is a modification of the homotopy perturbation method. The approach allows not only an actual periodic solution, but also the frequency of the problem as a function of the amplitude of oscillation. Three nonlinear oscillators including restoring force, the simple pendulum motion, the cubic Duffing oscillator, the Sine-Gordon equation are offered to clarify the effectiveness and usefulness of the proposed technique. This approach allows an effective mathematical approach to noise and uncertain properties of nonlinear vibrations arising in physics and engineering.

In this paper, we consider the following fractional Schr\”{o}dinger-Poisson system: \begin{equation*} \left\{ \begin{array}{ll} (-\Delta)^su+u+\lambda K(x)\phi u=a(x)|u|^{p-2}u+b(x)|u|^{2}u& \hbox{in $\mathbb{R}^3$,}\\ (-\Delta)^t\phi=K(x)u^2& \hbox{in $\mathbb{R}^3$,} \end{array} \right. \end{equation*} where $s,t\in(0,1)$, $\lambda>0$, $2

A document by Gongbao LI, written on Authorea.

We study the spectral properties of resonances of general Hamiltonians in the Born-Oppenheimer approximation. We prove that this study can be reduced to the one of a family of finite matrices of semiclassical h-pseudodifferential operators. More precisely, we show that any resonance which is close enough to the real axis can be obtained from the discrete spectrum of one of these matrixes.

A document by Wanassi WANASSI, written on Authorea.

In this paper, we consider a nonlinear plate (or beam) Petrovsky equation with strong damping and source terms with variable exponents. The exponents of nonlinearity _p_(⋅) and _q_(⋅) are given functions. By using the Banach contraction mapping principle the local existence of a weak solutions is established under suitable assumptions on the variable exponents _p_ and _p_. We also show a finite time blow up result for the solutions with negative initial energy.

In the ecological literature, many models for the predator-prey interactions consider the monotonic functional responses to describe the action of the predators. However, there exist antipredator behaviors which are best represented by non-monotonic functions. The mathematical results on the predator-prey models provide very useful information to understand the complex food webs; they also help to the insight of the mechanisms that govern the evolution of ecological systems. The aim of this paper is to show, the dynamics of a modified Leslie-Gower model, assuming a rational non-monotonic functional response or Holling type IV. A principal target is to compare the obtained properties with other cases, in which different non-monotonic functional responses are incorporated. The model is described by an autonomous bi-dimensional ordinary differential equation system (ODEs), assuming that the prey and predator growth functions are the logistic type. The proposed model is not defined in $(0,0)$; considering a topological equivalent system, it is possible that to prove the origin is a non-hyperbolic saddle point. We also have established, there are subsets of the parameter space in which: i) there exists a unique positive equilibrium point, ii) a heteroclinic curve exists. iii) two concentric limit cycles exist, the innermost unstable and the outermost stable. Numerical simulations are given to endorse the analytical results and to exhibit the richness of the dynamics in the system.

Over thirty species of littoral marine Gammaridea occur along the coasts of the North Atlantic. From one to several species can coexist in a single region. There is an evident, inverse relationship between egg incubation time and temperature (from 14 to > 120 days) and consequent trends in the size of the animals on reaching maturity (from 5 mm in warmer waters to 30 mm in the coldest ones) and in lifespan (from < 6 months to > 5 years). Littoral gammarids are a good example of the shrinking size effect of increasing temperatures and size-related species diversity. In large species the annual cohorts of the population (3 to 5 annual size groups) functionally replace the adults of smaller species. The ongoing warming of the European Arctic seas may extend the distribution limits of boreal species so that more Gammarus species may appear on northern coasts hitherto occupied by just one or at most two species.

Domestic ducks are considered to have been tamed from the mallard or a descendant of the mallard and the spot-billed duck. Domestic ducks show remarkable phenotypic variation in morphology, physiology and behaviour. However, the molecular genetics of the origin and phenotypic variation of ducks are still poorly studied. Here, we present mallard and spot-billed genomes and perform whole-genome sequencing on eight domestic duck breeds and eight wild duck species. Surprisingly, analyses of these data support a model in which domestic ducks diverged from their closest wild lineage (mallard ducks and spot-billed ducks) at the last glacial period (LGP, 100-300 kilo years ago (Kyr)). The wild lineage further speciated into mallard ducks and spot-billed ducks approximately 70 Kyr, whereas the domestic lineage population decreased through the LGP. A scan of wild duck genomes compared with domestic duck genomes identified numerous loci that may have been affected by positive selection in ancestral wild ducks after their divergence from domestic lineages. Function analyses suggested that genes usually affecting organ development and energy metabolism may involve long-distance flight ability. Further selective sweep analyses identified two genes associated with egg production and three genes related to feeding modulation under selection in domestic ducks. These analyses unravel a distinct evolutionary pattern of ducks and two wild duck de novo genomes, thus providing a novel resource for speciation studies.

BLK belongs to the family of SRC kinases (SFKs), and are diagnosed with the aid of the presence of an SH3 and SH2 regulatory domains of N-terminal to the catalytic kinase domain. BLK in signalling has a vast position in transmitting alerts via immunoglobulins and ends in pro-B to pre-B conversion, and in signalling for boom arrest and apoptosis downstream of the B-cellular receptor. We have performed a series of computational analysis on various aspects on BLK viz phylogenetic analysis, domain analysis, secondary structure prediction, charge distribution, prediction of the antigenic region and have executed structural analysis by first structure modelling and then its refinement, and active site prediction for better understanding of the human BLK as a drug target. Our study includes a detailed analysis and graphical representation of different domains, charge distribution, prediction of the antigenic region etc with corresponding sequence and its secondary structure for the pharmacological aspect of BLK which observed that Tulipa suaveolens is the most outed clade in the BLK and Human BLK is found to be very closed to Pongo Abelii through the phylogenetic tree assessment.

Objective: To contribute to the validation of the self-administered ALSFRS-R - European Portuguese version (ALSFRS-R: EP), and to analyse its reliability in order to enable its use by ALS patients in Portugal. Methods: The study was developed in 3 phases. Phase 1: Translation and cultural adaptation of the self-administered ALFRS-R; Phase 2: Content validation by study participants; Phase 3: Analysis of internal consistency and test - retest reliability. Results: According to a panel of experts (N=6), a CVI of 100% were obtained for all ALSFRS-R: EP items. A sample of 18 people with ALS (13 male) fulfilled the test and evaluated its items regarding its clarity, comprehension, difficulty and relevance, obtaining values with an average between 8.6 and 8.9, 8.7 and 8.9, 8.5 and 8.8, and 8.5 and 8.9, respectively. The instrument total score and its subscales presented good internal consistency (Cronbach’s α: from 0.72 to 0.92 in the test; from 0.70 to 0.95 in the retest) and reliability (Kendall tau: from 0.575 to 0.990). Considering the scale total score for the test, no statistical differences were observed between females and males nor between bulbar ALS and medullar ALS. The correlation between the total score and age showed to be significant and negative (-0.53). Conclusions: The Self-Administered ALSFRS-R: EP version was successfully translated, validated, and presented good to excellent reliability results. It will allow its use by Portuguese ALS patients and enabling their health professionals to monitor the disease progression at home.

The article From Electrica to Invariant Automatica, with subtitle System and Invariant Electric Model, compares well-known power equations and other energy equations, regardless of the physical nature of the energy (mechanical, thermal, thermonuclear etc.) and thus the author creates a universal measure for the concept of energy. On this basis, the universal concept of a system is defined as a pair of two elements of energy source and energy consumer. The user is a production facility, at the output of which a product of certain qualities (mechanical dimensions, temperature, pressure, concentration, pH, etc.) appears. The control of the energy flow to it depends functionally on these qualities and, in addition, on the efficiency of the system (speed, flow rate, number of objects per unit of time, etc.). In the second part of the article with subtitle Electromechanical Dualism. The Universality of Energetic Equations, with the help of modern altebra, is proved the versatility of the electrical model of the system

A semiclassical phase-space perspective of band- and topological-insulator regimes of 2D Dirac materials, and normal- and superradiant-phases of atom-field interacting models is given in terms of delocalization, entropies, and quantum correlation measures. From this point of view, the low-energy limit of tight-binding models describing the electronic band structure of topological 2D Dirac materials like phosphorene and silicene with tunable band gaps, share similarities with Rabi-Dicke and Jaynes-Cummings atom-field interaction models, respectively. In particular, the edge state of 2D Dirac materials in the topological insulator phase exhibits a Schrödinger cat structure similar to the ground state of two-level atoms in a cavity interacting with a one-mode radiation field in the superradiant phase. Delocalization seems to be a common feature of topological insulator and superradiant phases.

This is a follow-on paper from the Hutchison group, expanding on some previous work looking at correlations of molecular energy from a variety of levels of theory with results from high-level ab initio calculations. A new addition in this paper is a small set of ML methods, a welcome addition to the forcefield and electronic structure methods usually used in comparisons of this kind.The paper presents some interesting results, but is riddled with missing or misattributed data, typos, grammatical errors (particularly agreements for single and plural nouns) and errors in the references. The paper should be carefully corrected before resubmission.The key omission in the paper is any attempt to provide confidence in the deductions made about the differences in accuracy between the methods compared. Confidence intervals on each of the estimators, estimates of success rates and their errors, and pairwise hypothesis tests, at a minimum, must be added before publication. With this data in hand the new version can make quantitative estimates of the differences between the methods.