Background: Anaphylaxis is the most severe manifestation of allergic disorders. Diagnostic and understanding of molecular mechanisms need to improve. Extracellular vesicles (EVs) play a key role in cellular communication offering new possibilities to unravel patient-based particularities. The aim of this study is to analyze the protein profile of anaphylaxis-derived EVs providing a resource of potential markers for anaphylactic reactions, and to characterize their molecular mechanisms. Methods: EVs were isolated from 86 plasma samples (collected from 43 patients) during the acute phase of anaphylaxis (AnEVs) and at their baseline (BEVs). For comparison, EVs were characterized and their protein patterns were analyzed by mass spectrometry-based quantitative proteomics (LC-MS/MS). System Biology Analysis (SBA) was applied to identify main canonical pathways and molecules involved. In addition, in vitro permeability assays based on EVs-endothelial cells (ECs) were performed. Results: Differential proteomic analysis performed in 10 EVs paired patients’ samples identified 1206 proteins of which 99 were modulated in the AnEVs signature. CDC42, Ficolin-2 and S100A9 enrichment was confirmed in a larger cohort of patients. SBA revealed diverse group of immune proteins as the main canonical pathways altered in AnEVs. Thus, leukocyte extravasation and granulocyte adhesion-diapedesis processes stand out. In addition, marked-EVs from anaphylactic patients were captured by ECs decreasing the resistance of human endothelial monolayers. Conclusion: Our findings identify for the first time a differential EVs pattern signature in anaphylaxis revealing a source of potential biomarkers. Furthermore, these vesicles could participate in altered immune molecular mechanisms and present a role increasing vascular permeability.

Amazonian savannas are isolated patches of open habitats found within an extensive matrix of tropical forest. Climate in Amazonia is transitioning to a state where savannas are more likely to occur than forests, but the hydraulic functioning of savannas species in Amazonian vegetation remain unknown and unexplored. We measured 22 leaf, wood and hydraulic traits, including embolism resistance (as P50), hydraulic safety margin and isotope-based water use efficiency, for the seven dominant woody species (75% of biomass) in an Amazonian savanna plants. We found a wide variation in resistance to embolism (-1.66 ±0.06 MPa and -5.07±0.46 MPa) and structural anatomy with species investing in three different functional strategies to tolerance the drought. (1) species with high leaf succulence have less efficient water use increase Gmax, minimizing the risk for xylem. (2) Species that have higher embolism resistance by reinforcement of the intervascular walls of the longest vessels. (3) Species that decrease the spread of embolism by thickening of the membrane of the intervascular pit of short vessel elements. Our results suggest no unique dominant functional strategy among Amazonian savanna species illustrating the multiple ways to adapt to increasing of seasonality in those environments.

Background and Purpose One characteristic of tumor-infiltrating CD4+Foxp3+ regulatory T cells (Tregs) is high expression of tumor necrosis factor receptor II (TNFR2), a receptor that mediates the decisive effect of TNF in the activation and expansion of Tregs. There is increasing evidence that inhibition of TNFR2 can enhance anti-tumor immune responses. Therefore, we screened Chinese herbal extracts for their capacity to blockade of TNF-TNFR2 interaction. Experimental Approach The inhibitory effect of Chinese herbal extracts and their containing compounds on the biological consequence of TNF-TNFR2 interaction was initially examined with WEHI-13VAR cells and then verified by the primary TNFR2+ Tregs. The resultant small molecule TNFR2 inhibitor on the expansion of Tregs in tumor environment was investigated in mouse CT26 colon model. The effect of such compound on the efficacy of CpG oligodeoxynucleotide in the treatment of tumor was further evaluated with same model. Key Results The results showed that one Chinese herb extract was able to inhibit TNF/TNFR2-induced death of WEHI-13VAR cells and TNF-induced proliferation of TNFR2+ Tregs. Our subsequent study found that flavonoid compound scutellarin was responsible for the activity. Importantly, scutellarin treatment markedly enhanced the efficacy of tumor immunotherapy with CpG oligodeoxynucleotide in mouse CT26 colon cancer model. This effect of scutellarin was associated with the reduction of tumor-infiltrating TNFR2-expressing Tregs, and increased tumor infiltration of IFN-–producing CD8+ T cells. Conclusion and Implications Scutellarin has activities in the inhibition of Tregs expansion induced by TNF-TNFR2 interaction. Our result also suggests that scutellarin or its analogues may be useful as an adjuvant to enhance anti-tumor effect of immunotherapy.

Coronavirus belonging to family Coronaviridae is a large group of viruses causing respiratory and gastrointestinal diseases. The outbreak of 2019-novel coronavirus (2019-nCoV) has created panic in the whole world after being transmitted from Wuhan, China in December 2019. A large number of people are affected throughout the world that forced a solitary situation in the affected areas confining common people to their homes to prevent its spread. Cellular receptor in humans for 2019-nCoV are found to be same as for SARS-CoV (Severe acute respiratory syndrome coronavirus), the first human pandemic of 21st century, however, 2019-nCoV is highly contagious, virulent and mutable than the SARS-CoV. The most attractive site for vaccine development against novel2019 coronavirus is the spike glycoprotein which is crucial for receptor binding, membrane fusion via confirmational changes, virus internalization, host tissue tropism or spike inactivation through antibody induced destabilization. Severity and fatality of the current scenario has provoked the health care workers, scientists and pharmaceutical organizations to develop a vaccine to prevent its hazardous effects and transmission. First outbreak was in March 2020 after which the number of affected reduced that created a sigh of relief in the globe. Summer season was considered as one of the aspect combating the severity of spread of virus. For last few days, suddenly a huge outrage is capturing attention of the entire population of earth endangering lives of people irrespective of their ages and communities.

The INHALE-HEP meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled trials and early phase studies, to evaluate whether inhaled nebulised UFH in hospitalised patients with COVID-19 who do not require immediate invasive mechanical ventilation, significantly reduces intubation (or death, for patients who died before intubation) at day 28 compared to standard care alone. Objective: In keeping with best practice and with the published protocol, a pre-specified statistical analysis plan has been described and made public before completion of patient recruitment and data collection into the INHALE-HEP meta-trial. Methods: Our statistical analysis plan was designed by the INHALE-HEP executive committee and statisticians and approved by the INHALE-HEP steering committee. We reviewed the data collected as specified in the meta-trial protocol and collected in individual contributing studies. We present information pertaining to data collection, pre-specified subgroups, and study outcomes. Primary and secondary outcomes are defined, and additional subgroup analyses of pre-defined variables are described. Results: We have described our methods for presenting the trial profile and baseline characteristics, as well as our Bayesian approach to monitoring and meta-analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn. Conclusion: To minimise analytical bias, we have developed a statistical analysis plan and made this available to the public domain before completion of patient recruitment and data collection into the INHALE-HEP meta-trial.

Background: IgE–mediated allergic diseases have increased in the last decades. The most prevalent allergens from castor seeds are Ric c1 and Ric c3, isoforms of 2S albumin. These allergenic proteins cross-react with allergens from peanut, shrimp, fish, corn, gramineous, house dust, and tobacco. The usual allergy treatment employs antihistaminic and, immunotherapies. We propose an alternative immunotherapeutic approach, denoted “IgE-blockage” by L-Glutamic acid or modified-glutamic acid. Methods: Six compounds, D-glutamic acid, L-glutamic acid, N-methyl-L-glutamic acid, N-acetyl-L-glutamic acid, N- (4-nitrobenzoyl) -L-glutamic acid, and N-carbamyl-L-glutamic, were tested as a blocker. To evaluate motor coordination and the sedative/hypnotic activity of L-glutamic acid, a rota-rod test and a thiopental sodium-induced sleeping test were used. Results: the compounds, L- Glutamic acid and L-Nitrobenzoyl glutamic acid, were the most active compounds to block the interaction of castor allergens with IgE. These compounds also prevent cross-responses with allergens from food sources and inhalants that cross-react with them. In the sleeping test, the groups that received L-glutamic acid at doses of 10 and 30 mg/kg had a sleeping time similar to the vehicle control group. No changes in the animals’ behavior were observed and there was no difference between the L-glutamic acid groups and the vehicle control groups in the rota-rod test. Conclusion: L-glutamic acid and L-Nitrobenzoyl glutamic acid could be used as IgE blockers to prevent allergic diseases.

Abandoned agricultural fields are thought to accumulate soil organic matter after cultivation cessation. Most research on soil C and N sequestration has focused on the surface and overlooked their dynamics below 30 cm. With 13-year long-term surveys of 21 old field, we found soil C and N accumulated by 30.5 ± 6.5 g C m⁻² yr⁻¹ and 2.41 ± 0.49 g N m⁻² yr⁻¹ in the surface (0-20 cm) yet decreased by 64.6 ± 12.5 g C m⁻² yr⁻¹ and 6.83 ± 1.34 g N m⁻² yr⁻¹ in the subsurface (20-100 cm). Such C and N losses in subsurface soil can be attributed to the shallow root distribution, which is likely caused by the continuing dominance of non-native and shallow rooted C3 grasses and the lack of legumes after abandonment. Thus, vegetation changes are a legacy effect of agriculture that leads to ongoing soil C losses in abandoned agricultural fields.

Introduction Sepsis is one of the major causes of death in intensive care unit (ICU). One of the most important treatment for sepsis is antibiotic treatment. At the beginning antibiotics is chosen empirically after that is changed according to culture results or response to initial treatment. Nevertheless, only small number of culture positivity can be detected. The factors associated culture positivity are of interest in the critically ill patients. Therefore, we aim in our study to explore the factors associated with blood culture positivity especially blood glucose levels at the time blood culture sampling. Methods We perform this prospective observational study at the Intensive Care Unit of Dr. Suat Seren Chest Disease and Chest Surgery Training and Research Hospital between August 1, 2016 and January 1, 2017, in İzmir, Turkey. Two separate samples from opposite sides of each patient were obtained, and blood glucose was measured simultaneously with bed-side blood glucose measurement device by using the blood drawn for blood culture for each vial. The average of the two measurements was considered as the simultaneous blood glucose level of the patient. Results 174 patients were enrolled into the study, blood culture positivity was detected in 53 (30%) patients. In univariate analyzes, blood glucose levels, presence of central venous catheter, antibiotic treatment, vasoactive drug infusion and diabetes mellitus (DM) were associated with culture positivity. In multivariate analyze only DM was associated culture positivity (OR 5.63 [95% CI 1.99-15.91] p=0,001). Conclusion DM increase possibility of blood culture positivity. It stems from uncontrolled DM. Further studies are needed to evaluate this condition stems from uncontrolled DM or both uncontrolled and well-controlled DM.

Abstract The availability of accurate data on forest resources is an essential requirement for species documentation, community identification, and planning within the context of sustainable use of the forest. A survey of mammalian species was conducted in Yotyet/Yewezera Forest southern Ethiopia to assess their diversity and abundance in the area. Transect method was used to collect data for the study. Data was collected from the established line transect in each habitat from February 2019 to April 2019. A total of 553 individuals of 10 medium and large sized mammalian species distributed in to five orders and six families were recorded. Chlorocebus aethiops (42.9%) was the most abundant mammalian species followed by Colobus guereza (22.2%). Leptus starcki (1.6%), Traglaphus scriptus (2.9%), Crocuta crocuta (3.3%) were the less abundant species. The highest diversity of mammals was recorded from open grassland (H´=2.082; Simpson´s index of diversity (1-D) = 0.8626) and the less was from human plantations area (H´= 1.044; Simpson´s index of diversity (1-D) = 0.6311). Though, Yotyet/Yewezera community forest is with high potential of conserving biodiversity, it is not free from anthropogenic factors that threatened the biological components of it. Therefore, awareness should be created for the local people about the effects of forest destruction on the wildlife and start biodiversity conservation program in the area. Key words: Abundance, diversity, mammals, Yotyet/Yewezera forest, Southern Ethiopia

The novel COVID-19 spread around the world.Patients with malignant neoplasms are more susceptible to infection.Here we presents clinical cases of complex therapy of patients with with hemoblastosis and concomitant COVID-19 infection

Background: While patients with Wilms tumor (WT) have an overall survival greater than 90%, tumor rupture is associated with worse outcomes and can increase risk of abdominal recurrence to 20%1. Because our institutional rate of rupture is at least 2.5x higher than that found in literature, we conducted a retrospective chart review to understand the differences between our patient population and the population in literature2. Our aims were to 1) compare our patient demographics and outcomes, 2) describe correlations between preoperative, intraoperative, and pathologic diagnosis of rupture, and 3) compare our outcomes between upfront resection and neoadjuvant chemotherapy. Procedures: We reviewed charts from 2015 to 2019 and assessed: details of presentation, chemotherapy, operative and pathological findings, complications, and outcomes between patients with and without rupture. Results: Of 29 patients with WT, 9 had preoperative rupture by imaging and 8, all females, were confirmed surgically. Our rupture prevalence of 27.6% is higher than that in literature (11-13%.) Despite patients with rupture having more positive margins (50% vs. 19% non-ruptured), they had lower recurrence rates at one year (0 vs 19% non-ruptured) and improved survival mortality (100% vs. 90.5% non-ruptured). Neoadjuvant therapy and flank radiation compared to whole abdominal radiation did not change complication rates or outcomes. Conclusions: The high percentage of ruptured WT at our institution allowed for comprehensive review and revealed variations from literature. Patients with rupture had better outcomes than patients without rupture, with no difference comparing neoadjuvant chemotherapy to upfront resection and flank vs whole abdomen radiation.

Structural properties like the total energy, ionisation potential, excitation energies and transition probabilities for the first four magnetic dipolar (M1) excitations $1s^{2}$:$^{1}$S$^{e}\rightarrow1sns$:$^{3}$S$^{e}_{1}$ and magnetic quadrupolar (M2) excitations $1s^{2}$:$^{1}$S$^{e}\rightarrow1snp$:$^{3}$P$^{o}_{2}$ (n = 2,3,4,5) of helium atom endohedral to a fullerene cage have been estimated. Time dependent coupled Hartree-Fock(TDCHF) theory within variational scheme has been adopted for the detailed study of the excitation properties. The structural properties have been estimated by introducing an effective potential replacing that for the free atom, mimicking the fullerene environment which may be neutral, positive or negatively charged. Interesting behaviour of the properties of the confined He atom have been observed with respect to nature of the charge on fullerene cage. Results for the free He atom agree well with those available in the literature while those for the confined system have been reported for the first time.

Introduction: Cardiac magnetic resonance (CMR) is the gold standard for evaluating myocardial fibrosis. Few studies have explored the association between ventricular arrhythmias (VAs) and fibrosis in apparently normal hearts. We aimed to investigate the association between the occurrence and morphology of VAs and left ventricular late gadolinium enhancement (LV-LGE) in patients without known structural heart diseases. Methods: This study enrolled 78 patients with apparently normal hearts who underwent simultaneous 24-h ambulatory Holter electrocardiogram (ECG) and CMR examinations. The presence and extent of LGE was determined using CMR imaging and compared based on occurrence and morphology of VAs. The clinical characteristics were also recorded and calculated. Results: LV-LGE was observed in 19 (37.3%) and 4 (14.8%) patients with and without VAs, respectively (P=0.039). It was more frequently observed in patients with polymorphic VAs (P=0.024) and ST-segment depression (P=0.001), and its extent was greater in polymorphic VAs than monomorphic VAs, with a difference that approached significance (P=0.055). In multivariate analyses adjusted for other clinical variables, the presence of ST-segment depression (HR: 8.83; 95% CI: 2.23-35.50; P=0.002), drinking (HR: 6.84; 95% CI: 1.63-28.56; P=0.008), and polymorphic VAs (HR: 25.24; 95% CI: 3.88-164.06; P=0.001) were associated with greater prevalence of LV-LGE. Conclusion: In this cohort of patients without structural heart diseases, myocardial fibrosis was associated with multiple VA morphologies and ST-segment depression on Holter ambulatory ECG measurements.

Objective: Hereditary spherocytosis is the most common erythrocyte membrane disorder characterized by splenomegaly, jaundice and anemia. The aim of this study was to evaluate the demographics, clinical and laboratory findings and treatment responses of patients with hereditary spherocytosis. Material and Method: Data of patients under the age of 18 with a diagnosis of hereditary spherocytosis between 1989-2018 were examined retrospectively. Diagnosis was based on clinical history, physical examination, family history, presence of spherocytes in peripheral smear and osmotic fragility test. Demographic, clinical and laboratory features, family history, complications, and history of splenectomy and cholecystectomy were evaluated. Results: One hundred and one patients were included. The median (range) age at diagnosis was 38.0 (1-188) months. Mild, moderate and severe forms of hereditary spherocytosis were present in 29 (28.7%), 15 (14.9%) and 57 (56.4%) patients, respectively. Family history was investigated in 73 (72.3%) and 56 (76.7%) had a family history of hereditary spherocytosis. Ninety one patients had available physical examination results; of these 79 (86.8%) had splenomegaly, 53 (58.2%) pallor and 16 (17.6%) jaundice. Forty-five (44.5%) patients needed regular transfusions and most (78.9%) of these had severe spherocytosis. Although most patients did not require transfusion post-splenectomy, two of 45 (4.4%) patients continued to require transfusion. Transfusion dependence was significantly (p<0,001) higher in patients with severe spherocytosis. Conclusions: In hereditary spherocytosis splenomegaly, pallor and jaundice are the most common physical findings. Splenectomy is effective in reducing hemolysis and virtually abolishes further requirement for transfusion. Key words: hereditary spherocytosis, anemia, hemolytic anemia, children

Left atrial appendage aneurysm (LAAA) is a rare congenital anomaly which can be associated with cardiovascular morbidity and mortality by predisposing to atrial tachyarrhythmias, thromboembolism and cardiac failure. In this case report a patient presenting with supraventricular arrythmias and chest pain due to LAAA is presented. Surgical treatment was performed through median sternotomy with cardiopulmonary bypass through which the giant aneurysm of the left atrial appendage, extending to the apex of the left ventricle was surgically managed successfully. Surgical treatment is curative and proposed as the main treatment modality regardless of the presence or absence of symptoms.

We consider the problems of simultaneously identifying two unknowns. The wave propagation velocity and the memory of the layered medium will be determined. For their determination, two observations are used for how the boundary of the domain fluctuates. Main results are stability estimates and uniqueness theorems for the problems under consideration.

In this paper, we investigate the solvability of time conformable fractional equation set in a singular cylindrical domain in R^{N+1}. Some regularity results are obtained for the classical solutions by using the Dunford operational calculus

Let M be an R-module. If every essential submodule of M has a g-supplement in M, then M is called an essential g-supplemented (or briefly eg-supplemented) module. If every essential submodule has ample g-supplements in M, then M is called an amply essential g-supplemented (or briefly amply eg-supplemented) module. In this work, some properties of these modules are investigated. It is proved that every factor module and every homomorphic image of an amply eg-supplemented module are amply eg-supplemented. Let M be a projective and eg-supplemented module. Then every finitely M-generated R-module is amply eg-supplemented.

Constitutional Mismatch Repair Deficiency (CMMRD) is caused by a biallelic mutation on one of the four major mismatch repair (MMR) genes. It is a rare autosomal recessive syndrome that predisposes to childhood cancer. We present a 21-year-old African American with metachronous non-Hodgkin lymphoma during childhood, bone marrow transplant due to relapse, and stage IV duodenal adenocarcinoma as a young adult. His original presentation merited CMMRD screening. As many chemotherapy agents cause DNA damage and require an intact MMR system, early diagnosis could have anticipated the lymphoma relapse due to drug resistance and started timely screening for other malignancies.

In this paper, we study the blow-up of solutions to a semilinear double-wave equation with a power nonlinear term. By establishing an auxiliary function and using iteration methods associated with a differential inequality technique, the estimates of lifespan and blow-up of solutions are obtained.

Calculating a minimum spouting velocity for a given solid-fluid system has never been easy as the right choice of the correlation was difficult. It is shown in the present work that an analytical approximation for the exponent on the major influential parameters may be helpful if the derivation results from the basic force balance between solid and fluid. Nearly a dozen of earlier reported correlations are compared here with their key experimental details. Systematic experiments were performed using seven different spouted bed apparatus, nine different solid particles and two different spouting gases. Results from the analytical approximation, present experiments and the past reported correlations, a comprehensive correlation is proposed covering a wide range of variables. An industrial engineer or a scientist can now judiciously choose suitable exponent on the major influential parameters for a given set of spouted bed apparatus/ column, solid and fluid.

Water deficiency is one of the most major factors that limit plant growth and agricultural productivity. Previous studies showed the biomass and artemisinin content reduced significantly in A. annua plant under water scarcity. However, the molecular mechanism by which A. annua responds to drought stress is not well understood. In this study, AabZIP1 was identified to be involved in the responsive process to drought stress in A. annua. AabZIP1 could activate the expression of two wax biosynthesis genes, AaCER1 and AaCYP86A1, by directly binding to their promoters. Overexpression of AabZIP1 significantly promoted the expression of AaCER1 and AaCYP86A1 and led to enhanced cuticular waxes biosynthesis, thus significantly elevating the tolerance to water deficiency in A annua. Additionally, AabZIP1 positively regulates the expression of AaMYC2 by binding to its promoter, a MYC family transcription factor which positively regulates the expression of artemisinin biosynthesis genes, like ALDH1, DBR2 and CYP71AV1. Overexpression of AabZIP1 caused the upregulation of the expression of AaMYC2 and artemisinin biosynthesis genes, leading to an increase of artemisinin content. Taken together, our results indicate that AabZIP1 plays a positive role in the regulation of drought tolerance and artemisinin biosynthesis in A annua.

Objective: Platelet dysfunction has been shown to play a role in postoperative bleeding; however, it is not clear whether immature platelets (IP) can induce appropriate homeostasis to prevent excessive bleeding in patients undergoing CABG. This study investigated IP count (IPC), IP fraction (IPF) and mean platelet volume (MPV) throughout the hospitalization of patients undergoing CABG to elucidate their impact on postoperative bleeding and need for transfusion. Methods: Fifty consecutive patients undergoing elective CABG were included in this prospective study. All CABGs were performed by the same surgical team in a standardized fashion utilizing on-pump technique. IP and IPF were measured preoperatively, after the completion of surgery and at postoperative 1st,3rd, and 5th days. Whether need for transfusion was associated with IP, IPF, MPV and platelet count was the primary outcome measure of this study. Results: A significant increase in IPC and IPF was observed at the postoperative first day compared to baseline values. Preoperative IP and IPF were negatively correlated with intraoperative blood transfusion (p=0.017, and p=0.049, respectively). Duration of the operation, and preoperative hemoglobin and hematocrit levels were significantly correlated with the length of hospital stay. However, neither IP nor IPF were associated with the total amount of blood components used throughout the hospitalization, and they were also unassociated with the length of hospital stay. Conclusion: Although IPC and IPF are weakly correlated with postoperative drainage and blood transfusion frequency, they appear to have very little use –if any– in the prediction of postoperative bleeding in patients undergoing CABG

Background: Swine influenza is not only an economically important respiratory disease in swine, but also constantly poses a threat to human health. Hence, developing a rapid, sensitive and efficient detection method of swine influenza virus (SIV) is highly essential. Method: By aligning the HA gene sequences of SIV circulating in China in recent 10 years, a H1 primer-probe set targeting both Eurasian avian-like H1N1 (EA H1N1) and Pandemic 2009 H1N1 (Pdm09 H1N1) lineages plus a H3 prime-probe set targeting the prevalent human-like H3N2 (HL H3N2) subtype were designed, respectively. Further, a TaqMan-MGB based duplex one-step real time RT-PCR (RRT-PCR) assay was established, and the sensitivity, specificity and repeatability were evaluated. Results: The duplex RRT-PCR exhibited good sensitivity with the detection limit of 5 copies/μL HA plasmid for each of the EA H1N1, Pdm09 H1N1 and HL H3N2 subtype SIVs, and matched a detection accuracy of 94.4% (17/18) with traditional virus isolation through chicken embryo inoculation using experimentally infected mice lung samples. Besides, the method showed high repeatability both within-run and between-runs, and no cross-reactivity against some commonly circulated porcine viruses in China. Furthermore, the duplex RRT-PCR method revealed a relatively higher prevalent rate of H1 than H3 subtype SIV in 166 nasal swabs from pigs in some slaughterhouse during October~December, 2019. Conclusions: This developed assay could be very helpful for rapid differential detection and routine surveillance of EA H1N1, Pdm H1N1 and HL H3N2 subtype SIVs in China.