Rationale, aims and objectives Patients with pulmonary arterial hypertension (PAH) have progressive and disabling symptoms, as well as a burden of treatments and a difficult clinical evaluation that make health-related quality of life a particularly relevant endpoint in this disease. The objective of our study was to evaluate patient-reported outcomes of patients receiving specific treatment for PAH in a tertiary hospital using a specific questionnaire (Cambridge Pulmonary Hypertension Outcome Review-CAMPHOR). Methods A cross-sectional, observational, descriptive study was conducted. It included all patients receiving specific treatment for PAH in a tertiary hospital in Madrid, Spain. The inclusion period comprised between August to December 2019. CAMPHOR questionnaires containing three domains: symptoms, activities and quality of life were completed by the patients at the pharmacy consultation. Demographic and clinical variables, including WHO Functional Class (WHO FC), PAH-specific tests and hemodynamic parameters, were recorded. Non-parametric analyses to assess relations between variables and CAMPHOR domains were performed. Results Thirty-six patients consented to participate in the study and completed the questionnaire. Median scores for symptoms, activities, and quality of life domains were 5.5 (2.5 – 10), 8.0 (4.5 – 10.5) and 3.5 (1 – 7.5), respectively. Statistically significant differences were found in the three domains when comparing by WHO FC, in the activities domain for 6-meters walking test and in the quality of life domain for patients who had emergency visits or hospitalizations in the last year. Conclusions The CAMPHOR questionnaire could be useful as a complementary test to achieve an integrated evaluation of PAH patients, who could complete it easily during their routine pharmacy visits.

Cardiac mass is very rare. We reported a case of cardiac mass complicated with chronic thromboembolic pulmonary hypertension.

Introduction: Early right ventricular dysfunction in non-advanced patients with idiopathic pulmonary fibrosis has not been fully elucidated. Thus, we aimed to assess right ventricular functions in idiopathic pulmonary fibrosis patients and controls by speckle-tracking strain echocardiography at rest and peak exercise. Methods: We conducted a cross-sectional study in 20 idiopathic pulmonary fibrosis patients without oxygen use, blood oxygen saturation levels ≥92% at rest, and modified Medical Research Council score ≤3 and enrolled ten matched controls. Transthoracic echocardiography images were acquired at rest and during a cardiopulmonary exercise test. We assessed two-dimensional echocardiographic parameters and right ventricular function using the global longitudinal strain assessed by the two-dimensional speckle-tracking technique. Results: In the control group, we found normal values of global longitudinal strain (GLS) at rest and at peak exercise, the latter being much more negative (-23.6±2.2% and -26.8±3.1%, respectively; p<0.001). By contrast, GLS values in the idiopathic pulmonary fibrosis group increased from -21.1±3.8% at rest to -17.0±4.5% at peak exercise (p<0.001). The exercise revealed a difference between the two groups as the mean GLS values moved during peak exercise in opposite directions. Patients with idiopathic pulmonary fibrosis worsened, whereas control patients experienced improved right ventricular contractility. Conclusions: Right ventricular dysfunction was unveiled by speckle-tracking echocardiography during exercise in non-advanced idiopathic pulmonary fibrosis patients. We suggest that this reflects an inadequate right ventricular-arterial coupling decreasing the right ventricular longitudinal contraction during exercise in these patients. This parameter may be useful as an early index of suspected pulmonary hypertension.

Evaporation is the key to the basin’s water cycle. Agricultural irrigation has resulted in a significant variation of regional potential evaporation (Epen). The spatiotemporal variation of Epen and the influencing factors in the natural, agricultural, and desert areas in different developmental stages of irrigation in the Heihe River Basin (HRB) from 1970 to 2017 are comparatively analyzed in this study. This work focused on the correction effect of irrigation on the variation of Epen. The agricultural water consumption in HRB significantly varied around 1998 due to the agricultural development and water policy. Under the influence of irrigation, the annual variation of Epen in the agricultural, natural, and desert areas was significantly different. From 1970 to 1998, the annual trend slope of Epen in the natural area only reduced by 1 mm decade-1, while that in the agricultural area significantly decreased by 39 mm decade-1. After the implementation of water-saving irrigation, the Epen in the natural and agricultural areas increased by 11 and 54 mm decade-1, respectively, from 1998 to 2017. In contrast with the natural and agricultural areas, Epen in the desert area decreased by 80 mm decade-1 from 1970 to 1998 and continuously decreased by 41 mm decade-1 from 1998 to 2017. However, the regulatory effect of irrigation on Epen in the desert area started to manifest due to the expansion of the cultivated land area in the desert area from 2010 to 2017. Irrigation has a significant regulatory effect on the variation of Epen in HRB. The regulatory effect is mainly reflected on the aerodynamic term (Eaero). The analytical results of the main meteorological factors affecting Epen in different regions indicated that the main meteorological factors influencing the variation of Epen in each region are the wind speed 2 m above the surface (U2) and the water vapor pressure difference (VPD).

Meta-analyses often encounter studies with incompletely reported variance measures (e.g. standard deviation values) or sample sizes, both needed to conduct weighted meta-analyses. Here, we first present a systematic literature survey on the frequency and treatment of missing data in published ecological meta-analyses showing that the majority of meta-analyses encountered incompletely reported studies. We then simulated meta-analysis data sets to investigate the performance of 14 options to treat or impute missing SDs and/or SSs. Performance was thereby assessed using results from fully informed weighted analyses on (hypothetically) complete data sets. We show that the omission of incompletely reported studies is not a viable solution. Unweighted and sample size-based variance approximation can yield unbiased grand means if effect sizes are independent of their corresponding SDs and SSs. The performance of different imputation methods depends on the structure of the meta-analysis data set, especially in the case of correlated effect sizes and standard deviations or sample sizes. In a best-case scenario, which assumes that SDs and/or SSs are both missing at random and are unrelated to effect sizes, our simulations show that the imputation of up to 90% of missing data still yields grand means and confidence intervals that are similar to those obtained with fully informed weighted analyses. We conclude that multiple imputation of missing variance measures and sample sizes could help overcome the problem of incompletely reported primary studies, not only in the field of ecological meta-analyses. Still, caution must be exercised in consideration of potential correlations and pattern of missingness.

At a time when political protesting regarding racial injustice is commonly seen, medical professionals ought to recognize when racial and ethnic insensitivity may exist in our collective medical practice. A case in point relates to the use of prediction models for successful vaginal trials of labor after Cesarean (VTOL). 1-3Such algorithms can include verifiable correlates to vaginal births after Cesarean (VBAC), such as prior vaginal births, estimated fetal weight (EFW), persistent cesarean indications, body mass index (BMI), and even type of labor onset. The accuracy of these algorithms used to predict successful VBAC in a patient contemplating a VTOL has been recently questioned. 4-6 The inclusion of a racial component may be of questionable value here, since the anthropomorphic indicators of pelvic dimensions are less clear cut, 7especially when soft tissue description may offer a different correlation to the capacity for vaginal delivery. 8Although this last reference examined the obligate contribution of the soft tissues to the birth canal dimensions beyond its bony limitations, it related this to the prediction of soft tissue injuries. It nonetheless describes the consequential role of the pelvic soft tissues as part of the birth canal, unrelated to the possibly genetically determined bony pelvis dimensions. Pertinent to this discussion is the notion that Race, and ethnicity, have a role in determining vaginal delivery capability (e.g. in VBAC), when a sociodemographic basis may be confused with a biologically defined one.Measurement of the bony pelvic dimensions with magnetic resonance imaging (MRI), relating to an individual’s Race, has revealed the usual range as would be expected in any population, somewhat correlated with Race. Whether these described dimensions (e.g. inter-tuberous or ischial spinous diameter or pelvic inlet size) meaningfully correlates with the capacity to vaginally deliver, is open to some question, since there may be an essential role of the pelvic soft tissues (e.g. the levator muscles of the pelvic floor) with regard to vaginal delivery capability. X-Ray pelvimetry, and pelvimetry through other imaging modalities, has long been abandoned as a predictor of the capacity to vaginally deliver, due to its repeated documented failure.9 So, the inclusion of Race or ethnicity in an algorithm used to predict VBAC success, may inappropriately be using this demographic indicator. When the use of this specific factor (i.e. race/ethnicity) in a prediction model was shown to not be successful, the interpretation was simply articulated as “not predictive of VBAC success” and “unexpected”.10 In fact though, the underestimation of the probability of a successful VBAC because of a patient’s assignment of ethnicity or race, should be highlighted, as the ramifications of such counseling of a low probability of success, is significant when it can be shown to be inaccurate.This is of considerable importance since these prediction models can influence shared decision-making. The tendency to desire having a vaginal birth has been shown to correlate with certain racial/ethnic groups, and this influence is indeed relevant.11 The relationship of VBAC success prediction in the Latina community is particularly worthy of note, given some reported disparate findings.11 Interestingly, whatever the complex interactions of the pelvic bony dimensions and soft tissue dynamics are, the vaginal birth statistics do not appear to show significant differences between women in different racial/ethnic groups, in the United States. 12 The use of racial identity may not therefore be statistically relevant to any of the algorithms used for successful VTOL prediction. If encouragement of vaginal births is desirable when appropriate, then perhaps this racial categorization should be avoided. At least, we may need to properly establish and validate these algorithms within appropriately selected populations and follow described prediction model development.13

The study investigates the possibility to parameterize a hydrological model for remote high-altitude permafrost basin based on the data of historical short-term observations conducted in 1957-1959 at the Suntar-Khayata research station (Eastern Siberia) and simulate the changes of runoff observed in recent decades in the region. The Hydrograph model is applied as it has the advantage of using observed physical properties of landscapes as its parameters. The developed parametrization of the goltsy landscape is verified by the results of simulations of variable states of snow and frozen ground. Continuous simulations of streamflow with daily time step are conducted for the period of 1957-2012 at the Suntar River basin (area 7680 km2, altitude 828-2794 m) with average and median values of Nash-Sutcliff criteria reaching 0.58 and 0.67 respectively. The results of simulations have shown that the largest part of runoff (about 70%) is formed in the high-altitude area which takes only 44% of the Suntar River basin area. Simulated series of streamflow reproduce the patterns of recently observed changes, including the increase of low flow, by magnitude of trends and their change period, suggesting that the increase of the increase of liquid precipitation share in autumn months due to air temperature rise can be important factor of streamflow changes in the region. The data presented in the paper are unique for the vast mountainous parts of North-Eastern Eurasia which play important role in general climate circulation. The results indicate that if the assessment of hydrological model parameters is based on observation data instead of calibration, the models can be used in the tasks of studying the response of river basins to climate change with more confidence.

Polyene polyketides amphotericin B (AMB) and nystatin (NYS) are important antifungal drugs. Thioesterases (TEs), located at the last module of PKS, control the release of polyketides by cyclization or hydrolysis. Intrigued by the tiny structural difference between AMB and NYS, as well as the high sequence identity between AMB TE and NYS TE, we constructed four systems to study the structural characteristics, catalytic mechanism, and product release of AMB TE and NYS TE with combined MD simulations and QM/MM calculations. The results indicated that compared with AMB TE, NYS TE shows higher specificity on its natural substrate and R26 as well as D186 were proposed to a key role in substrate recognition. The energy barrier of macrocyclization in AMB-TE-Amb and AMB-TE-Nys systems were calculated to be 14.0 and 22.7 kcal/mol, while in NYS-TE-Nys and NYS-TE-Amb systems, their energy barriers were 17.5 and 25.7 kcal/mol, suggesting the cyclization with their natural substrates were more favorable than that with exchanged substrates. At last, the binding free energy obtained with the MM-PBSA.py program suggested that it was easier for natural products to leave TE enzymes after cyclization. And key residues to the departure of polyketide product from the active site were highlighted. We provided a catalytic overview of AMB TE and NYS TE including substrate recognition, catalytic mechanism and product release. These will improve the comprehension of polyene polyketide TEs and benefit for broadening the substrate flexibility of polyketide TEs.

As a bioinformatic strategy, the present study was designed to use a network pharmacology analysis to uncover the pharmacological function and mechanism of puerarin to treat novel coronavirus pneumonia (NPC). Following methodological platforms, all theoretical and pivotal targets, anti-NPC mechanism of puerarin were filtrated and disclosed. As results, the pivotal targets of puerarin to treat NPC were collected and identified, comprising of EGFR, TNF, TP53, CASP3, RELA, FOS, CASP8, PTGS2, IL2, PRKCB, BCL2, PRKCA, NOS3, PPARG. Functionally, the anti-NPC action of puerarin was associated with suppression of oxidative stress and inflammatory cascades, cell apoptosis. Mechanically, the signaling pathways of puerarin to treat NPC were uncovered, including modulation of the pathways of Apoptosis, IL-17 signaling, MAPK signaling, TNF signaling. Molecular docking data illustrated the binding capacity of puerarin with NPC, and effective anti-NPC activity of puerarin. Taken together, our current network pharmacology-based findings revealed the pharmacological biotarget and mechanism of puerarin to treat NPC. Further, the bioinformatics findings elucidated that some of these 14 pivotal targets might serve as the potential molecular markers for detecting NPC, a rapidly emerging and evolving disease.

Clock genes exhibit substantial control over gene expression and ultimately life-histories using external cues such as photoperiod, and are thus likely to be critical for adaptation to shifting seasonal conditions and novel environments as species redistribute their ranges under climate change. Coding trinucleotide repeats (cTNRs) are found within several clock genes, and may be interesting targets of selection due to their containment within exonic regions and elevated mutation rates. Here, we conduct inter-specific characterization of the NR1D1 cTNR between Canada lynx and bobcat, and intra-specific spatial and environmental association analyses of neutral microsatellites and our functional cTNR marker, to investigate the role of selection on this locus in Canada lynx. We report signatures of divergent selection between lynx and bobcat, with the potential for hybrid-mediated gene flow in the area of range overlap. We also provide evidence that this locus is under selection across Canada lynx in eastern Canada, with both spatial and environmental variables significantly contributing to the explained variation, after controlling for neutral population structure. These results suggest that cTNRs may play an important role in the generation of functional diversity within some mammal species, and allow for contemporary rates of adaptation in wild populations in response to environmental change. We encourage continued investment into the study of cTNR markers to better understand their broader relevance to the evolution and adaptation of mammals.

Diffuse intrinsic pontine glioma (DIPG) is the most frequent brainstem tumor in children. All therapeutic efforts are palliative, being focal irradiation the only therapy capable of reducing temporarily tumor volume. The vast majority of patients succumb to their disease during the first 2 years after diagnosis usually due to local progression. At first relapse, focal re-irradiation has shown to provide clinical and radiologic benefits. There are no reports of craniospinal irradiation (CSI) as a rescue regimen when progression is local and disseminated. We report a patient treated with CSI at metastatic progression showing clinical and radiological response with good tolerance.

Objective: To explore the correlation between methylenetetrahydrofolate reductase (MTHFR) 677C→T polymorphism and high-risk pregnancy(HRP), and to establish a useful HRP management model during the perinatal period. Design:Retrospective cohort study Setting:The Fifth Hospital of Sun Yat-sen University Population:All women gave birth in the obstetrics departmen between 2018 and 2020. Methods:Using polymerase chain reaction and restriction fragment length polymorphism analysis (PCRRFLP) method to detect MTHFR677C→T genotype. Screening is base on whether the maternal has diagnosis HRP and have a regular antenatal care. The correlation between HRP and MTHFR677C→T polymorphism explained by chi-square test and the logistic regression. Main Outcome Measure: The alleles and genotypes of MTHFR 677C→T and the prevalence and classification of HRP. Results:A total of 2,372 were eventually enrolled, including 584 cases in the HRP group and 737 cases in the control group. The MTHFR 677C→T allele was in Hardy- Weinberg equilibrium(P>0.05). The MTHFR 677C→T polymorphism and allele (T) were associated with HRP (P<0.05).To be specific, they associated with Hypertensive disorders of Pregnancy(HDP), Pregnancy with thyroid disease, gestational anemia and Preterm birth(PTB)(P<0.05). After adjusting for confounders, the mutant genotype (C/T+T/T) remained a susceptibility factor for HDP and PTB(P<0.05). The allele (T) was associated with HDP, Gestational diabetes mellitus and PTB(P<0.05). Conclusions:The MTHFR 677C→T polymorphism was associated with HRP, especially HDP and PTB. It is necessary to establish a useful model to manage the women during the perinatal period. Funding: None Keywords:high-risk pregnancy, MTHFR677C→T, pregnancy comorbidities. Tweetable abstract:MTHFR 677C→T polymorphism is associated with high-risk pregnancy.

Background: Hypophosphatemia is an increasingly recognized side-effect of ferric carboxymaltose (FCM) and possibly iron isomaltoside/ferric derisomaltose (IIM), which are used to treat iron deficiency. Objective: To determine frequency, severity, duration and risk factors of incident hypophosphatemia after treatment with FCM and IIM. Data Sources: A systematic literature search for articles indexed in EMBASE, PubMed and Web of Science in years 2005 to 2020 was carried out using the search terms ‘ferric carboxymaltose’ OR ‘iron isomaltoside’. Study Selection: Prospective clinical trials reporting outcomes on hypophosphatemia rate, mean nadir serum phosphate and/or change in mean serum phosphate from baseline were selected. Data Extraction: Hypophosphatemia rate and severity were compared for studies on IIM vs. FCM after stratification for chronic kidney disease. Meta-regression analysis was used to investigate risk factors for hypophosphatemia. Results: Across the 42 clinical trials included in the meta-analysis, FCM induced a significantly higher incidence of hypophosphatemia than IIM (47%, 95% CI 36-58% vs. 4%, 95% CI 2-5%), and significantly greater mean decreases in serum phosphate (0.40 versus 0.06 mmol/L). Hypophosphatemia persisted at the end of the study periods (maximum 3 months) in up to 45% of patients treated with FCM. Meta-regression analysis identified low baseline serum ferritin and transferrin saturation, and normal kidney function as significant predictors of hypophosphatemia. Interpretation: FCM is associated with a high risk of hypophosphatemia, which does not resolve for at least 3 months in a large proportion of affected patients. More severe iron deficiency and normal kidney function are risk factors for hypophosphatemia.

One of the problems currently faced in the management of SARS-CoV2 infection is the absence of specific treatments that have proven their usefulness and their safety in studies with statistical validity, which allows to justify on reasoned evidence its use. In the case of paediatric patients although there are no serious cases in proportion to adults, there is the ethical limitation of not having reliable data to be able to justify therapeutic interventions on scientific evidence and to date there are few studies that analyze the safety of certain drugs and have not been included in paediatric groups in the evaluation of the use of COVID-19 vaccines.

In this work, we develop a new mathematical model to evaluate the impact of drug therapies on autoimmunity disease. We describe the immune system interactions at the cellular level, using the kinetic theory approach, by considering self-antigen presenting cells, self-reactive T cells, immunosuppressive cells and Interleukin-2 (IL-2) cytokines. The drug therapy consists of an intake of Interleukin-2 cytokines which boosts the effect of immunosuppressive cells on the autoimmune reaction. We also derive the macroscopic model relative to the kinetic system and study the wellposedness of the Cauchy problem for the corresponding system of equations. We formulate an optimal control problem relative to the model so that the quantity of both the self-reactive T cells that are produced in the body and the Interleukin-2 cytokines that are administrated is simultaneously minimized. Moreover, we perform some numerical tests in view of investigating optimal treatment strategies and the results reveal that the optimal control approach provides good-quality approximate solutions and shows to be a valuable procedure in identifying optimal treatment strategies.

In this paper, we study blow-up phenomena of the following p-Laplace type nonlinear parabolic equations under nonlinear mixed boundary conditions and u = 0 on Γ₂ × (0, t*) such that Γ₁ ∪ Γ₂ = ∂Ω, where f and h are real-valued C¹-functions. To discuss blow-up solutions, we introduce new conditions: For each x ∈ Ω, z ∈ ∂Ω, t > 0, u > 0, and v > 0, for some constants α, β₁, β₂, γ₁, γ₂, and δ satisfying where ρm := infw > 0ρ(w), P(v)=∫₀vρ(w)dw, F(x, t, u)=∫₀uf(x, t, w)dw, and H(x, t, u)=∫₀uh(x, t, w)dw. Here, λR is the first Robin eigenvalue and λS is the first Steklov eigenvalue for the p-Laplace operator, respectively.

Background: As of March 31, 2020, about 82,545 COVID-19-infected patients in China have been confirmed. Several observational studies have reported clinical characteristics of pneumonia caused by COVID-19 in China. But there are doubts about the clinical significance of differences reported in the different studies. The objective of this paper is to meta-analyze all available data from observational studies in China to enable an objective reappraisal of the clinical characteristics. Methods: PubMed, CNKI, EMBASE, and Cochrane Library were searched. Observational studies were included if they reported information on clinical characteristics of COVID-19-infected pneumonia. Statistical heterogeneity was assessed using the I2 test, with a value ≥ 50% indicating a substantial level of heterogeneity. Results: Pooled results exhibited that the proportion of male (58%) was higher in patients with COVID-19-infected pneumonia. Fever (89%), cough (74%), fatigue (44%), and shortness of breath (31%) were the common clinical manifestations. Cardiovascular disease (8%), endocrine system disease (9%), and digestive system disease (5%) were the common comorbidities. Moreover, hypertension (29%), endocrine system disease (16%), and cardiovascular disease (8%) were the most common comorbidities in severe patients. Acute cardiac injury (5%), ARDS (11%), shock (3%), and AKI (2%) were the common complications. Conclusions: Men may be more susceptible to COVID-19. The people with hypertension and endocrine system disease are more likely to develop severe pneumonia. The most common symptoms are fever and cough. The heart and kidneys may be also important organs for the COVID-19 to attack in addition to the lungs. Most patients have bilateral imaging abnormalities.

Chronic inflammatory diseases cause anemia of inflammation (AI). This causes impaired immune-mediated regulation of hepcidin and several cytokines, which play a major role in iron homeostasis, accelerates turnover of red blood cells, and affects the activity of erythropoietin (EPO), thereby reducing levels of hemoglobin and iron.1 Asthma is one of common allergic diseases caused by disturbance of the immune system,2 and this chronic inflammatory condition could cause systemic inflammation.3 Several researches have recently shown that asthma association with the increased prevalence of anemia.4,5 No studies, however, have been conducted on whether severe or uncontrolled asthma can more increase the prevalence of anemia.We hypothesized that patients with severe asthma were more likely to have an active inflammatory condition, which may increase the prevalence of anemia. Therefore, this study aims to evaluate whether the prevalence of anemia in pediatric asthma patients differs according to asthma control or severity.98% of Koreans are enrolled in the universal health insurance system, and all medical information is reported to the Health Insurance Review Agency (HIRA). In this study, 10% (~1,100,000) of patients under the age of 20 provided by HIRA were analyzed using a dataset constructed by random stratification based on age and sex (HIRA-PPS-2016).6 We included patients younger than 18 years and patients prescribed asthma medications with diagnosis of asthma (eTable1, eTable2). Patients diagnosed with anemia other than iron deficiency anemia (IDA) or AI were excluded. We classified the severe asthma group who were diagnosed with asthma exacerbation at least once a year or asthma diagnosis with systemic steroids, and the rest were defined as the non-severe asthma group. Binary logistic regression was carried out by applying inverse probability of treatment weighting (IPTW) using the propensity score. To calculate the predicting propensity score, we used a multivariable logistic regression model to estimate the probability of each patient, including confounders (eTable1). Odds ratio (OR) with 95% confidence interval (CI) are reported for association anemia and asthma severity.A total of 236,429 pediatric patients were included in the study. The flow diagram for the study subject inclusion is shown (Fig. 1) and the characteristics of the two groups of patients were similarly adjusted after applying IPTW (eTable3). The increased prevalence of anemia in patients with severe asthma was expressed OR of 1.56 (95% CI, 1.49-1.64; P < .001) (Table 1). The association between anemia and asthma severity in children, male, female, or patients under health insurance was expressed OR of 1.63 (95% CI, 1.55-1.71; P < .001), 1.59 (95% CI, 1.49-1.70; P <.001), 1.53 (95% CI, 1.42-1.64; P < .001), and 1.56 (95% CI, 1.49-1.64; P < .001), respectively. There were no associations between anemia and severe asthma in adolescents and patients under medical aid (Table 1).The prevalence of anemia in patients who experienced exacerbation of asthma or with systemic steroid was analyzed higher than other asthma patients. This was the same even after adjusting for other confounding factors in the two patient groups. Previous study suggested that the correlation between the two diseases in those groups may have been insignificant since adolescent patients or patients under medical aid program may have different medical service usage patterns from those of general patients.5We do not monitor anemia for asthma patients in general, and the guidelines do not present it in this regard. However, anemia negatively affects pediatric patients’ growth, cognitive abnormalities, and poor quality of life.7,8 In addition, in the case of AI, treatment or control of the underlying disease takes precedence over the treatment of anemia rather than simply administering iron or EPO.9 In addition, it was reported that in patients with high hepcidin, an index that can distinguish between AI and IDA, administration of EPO or iron administration was less or non-response to the treatment of anemia.11-12 Therefore, it might be recommended to monitor and treat anemia since the prevalence of anemia may increase in pediatric patients with severe asthma.This study has some limitations. First, we reported the association between severe asthma and anemia which is not the causality. Secondly, since we included patients diagnosed with IDA, the influence of patients with isolated IDA cannot be ruled out. Nevertheless, our study has several strengths including a large sample size and statistical adjustments with propensity weighting.To our knowledge, this is the first study to show that severe asthma has a stronger association with anemia compared to non-severe or controlled asthma. This suggests that it may be necessary to more closely monitor anemia in patients with severe asthma. Further study is needed to better understand the etiology that severe asthma causes more AI.

Since December 2019 that coronavirus pandemic (COVID-19) has hit the world, with over 13 million cases recorded, only a little above 4.67 percent of the cases have been recorded in the continent of Africa. The percentage of cases in Africa rose significantly from 2 percent in the month of May 2020 to above 4.67 percent by the end of July 15, 2020. This rapid increase in the percentage indicates a need to study the transmission, control strategy, and the dynamics of COVID-19 in Africa continent. In this study, a nonlinear mathematical model to investigate the impact of asymptomatic cases on the transmission dynamics of COVID-19 in Africa is proposed. The model is analyzed, the reproduction number is obtained, the local, as well as the global, asymptotic stability of the equilibria were established. We investigate the existence of backward bifurcation and we present the numerical simulations to verify our theoretical results.

As a key cellular sensor, the TRPV1 channel undergoes a gating transition from a closed state to an open state in response to many physical and chemical stimuli. This transition is regulated by small-molecule ligands including lipids and various agonists/antagonists, but the underlying molecular mechanisms remain obscure. Thanks to recent revolution in cryo-electron microscopy, a growing list of new structures of TRPV1 and other TRPV channels have been solved in complex with various ligands including lipids. Toward elucidating how ligand binding correlates with TRPV1 gating, we have performed extensive molecular dynamics simulations (with cumulative time of 20 μs), starting from high-resolution structures of TRPV1 in both the closed and open states. By comparing between the open and closed state ensembles, we have identified state-dependent binding sites for small-molecule ligands in general and lipids in particular. We further use machine learning to predict top ligand-binding sites as important features to classify the closed vs open states. The predicted binding sites are thoroughly validated by matching homologous sites in all structures of TRPV channels bound to lipids and other ligands, and with previous functional/mutational studies of ligand binding in TRPV1. Taken together, this study has integrated rich structural, dynamic, and functional data to inform future design of small-molecular drugs targeting TRPV1.

Anopheles coluzzii is a major malaria vector throughout its distribution in west-central Africa. Here we present a whole-genome resequencing study of 77 specimens from eight localities, that covers a large part of this species’ range, including three islands in the Gulf of Guinea: Bioko, São Tomé and Príncipe. Population genomic analyses encompassed structure of mainland populations, of island populations and connectivity between island and mainland populations. Three genetic clusters were found among mainland populations and genetic distances among all populations fit an isolation-by-distance model. Genomic analyses were applied to estimating the demographic history and ancestry (cross-coalescence) for each island. Taken together with the unique biogeography and history of human occupation for each island they present a coherent explanation underlying contemporary levels of genetic isolation between mainland and island populations and among island populations. We discuss the relation of our findings to the suitability of São Tomé and Príncipe islands as candidate sites for potential field trials of genetic-based malaria control strategies.

Although much of what we know about the genetic basis of herbicide resistance has come from detailed investigations of monogenic adaptation at known target-sites, the importance of polygenic resistance has been increasingly recognized. Despite this, little work has been done to characterize the genomic basis of herbicide resistance, including the number and distribution of involved genes, their effect sizes, allele frequencies, and signatures of selection. Here we implement genome-wide association (GWA) and population genomic approaches to examine the genetic architecture of glyphosate resistance in the problematic agricultural weed, Amaranthus tuberculatus. GWA correctly identifies the gene targeted by glyphosate, and additionally finds more than 100 genes across all 16 chromosomes associated with resistance. The encoded proteins have relevant non-target-site resistance and stress-related functions, with potential for pleiotropic roles in resistance to other herbicides and diverse life history traits. Resistance-related alleles are enriched for large effects and intermediate frequencies, implying that strong selection has shaped the genetic architecture of resistance despite potential pleiotropic costs. The range of common and rare allele involvement implies a partially shared genetic basis of non-target-site resistance across populations, complemented by population-specific alleles. Resistance-related alleles show evidence of balancing selection, and suggest a long-term maintenance of standing variation at stress-response loci that have implications for plant performance under herbicide pressure. By our estimates, genome-wide SNPs explain a near comparable amount of the total variation in glyphosate resistance to monogenic mechanisms, indicating the potential for an underappreciated polygenic contribution to the evolution of herbicide resistance in weed populations.

Isoniazid for 6-9 months is the most widely used form of tuberculosis (TB) preventive treatment. We aimed to assess the side effects of isoniazid by using the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and uric acid (SUA) in children and adolescents receiving long term isoniazid for latent tuberculosis infection. The study included children ≤18 yrs of age who underwent TB preventive treatment with isoniazid (IPT) between 2015 and 2019 at an university hospital. Serum transaminase, SUA, urea, and creatinine levels of patients were measured before the initiation of IPT, 15th day, and once a month during treatment. Patients with either ALT, AST, or SUA results above cut-off levels during treatment were evaluated. The final values in follow up were included in the analysis of the data. A total of 141 children who underwent IPT were included. Seventy children had family members with confirmed tuberculosis disease and 71 children had TST positivity. SUA increased above cut-off values in 16 children (11.3%) and half of them had uric acid levels over 7 mg/dL. The median duration of the development of hyperuricemia was 4.0 months. ALT or AST increased above cut-off values in 23 children (16.3%). ALT was above cut-off values in 7 patients, AST was high in 20 patients. The median duration to the development of AST and/or ALT levels above cut-off was 4.0 months. Two patients had hepatotoxic transaminase levels. Three patients had both elevated transaminases and SUA levels. İsoniazid may also cause hyperuricemia beside elevation in transaminases in children.

CT Colonography was performed after difficulty passing the stricture at colonoscopy. On imaging, the stricture was concerning for neoplasm (Fig 1). The patient underwent a segmental colectomy with histological analysis of the stricture demonstrating endometrial tissue(Fig 2.). The cause of abdominal pain was therefore secondary to extrapelvic endometriosis.