Having proper correlations for hydrodynamic forces is essential for successful CFD-DEM simulations of a fluidized bed. For spherical particles in a fluidized bed, efficient correlations for predicting the drag force, including the crowding effect caused by surrounding particles, are already available and well tested. However for elongated particles, next to the drag force, the lift force and hydrodynamic torque also gain importance. In this work we apply recently developed multi-particle correlations for drag, lift and torque in CFD-DEM simulations of a fluidized bed with spherocylindrical particles of aspect ratio 4 and compare them to simulations with widely used single-particle correlations for elongated particles. Simulation results are compared with previous magnetic particle tracking (MPT) experimental results. We show that multi-particle correlations improve the prediction of particle orientation and vertical velocity. We also show the importance of including hydrodynamic torque.

In this paper, the 3D modeling and optimization of a commercial hot wall vertical reactor for SiC coating is presented to investigate the effect of various process parameters on the hydrodynamics stability of the CVD reactor. The correlation between experimental and simulated results was established by tuning the kinetic parameters for the surface reaction. Besides, the incorporation of various dimensional numbers such as Reynolds number (Re), Péclet number (Pe), and Grashof number (Gr) enabled the systematic investigation of the effect of the natural convection phenomena on film growth performance. It was found that the buoyancy-driven flow can occur inside the reactor at high Reynolds number and Gr/Re2 ratio. The process optimization was performed using response surface methodology (RSM) to obtained desired film quality. The CFD-RSM combined approach allowed a significant reduction in the number of experiments and simulations required for the optimization of the CVD process.

A rapid and efficient method for the simultaneous detection of lignans (sesamol, sesamin, sesamolin) and tocopherols (α-tocopherol, γ-tocopherol, δ-tocopherol) in sesame oil by reversed-phase high-performance liquid chromatography (RP-HPLC) has been established. The samples were ultrasonically extracted in methanol and eluted via a methanol-water gradient on a reversed-phase C18 column with UV/Vis detection. The recoveries of the six analytes ranged from 88.22% to 100.13%, and the relative standard deviations (RSD, n = 6) ranged from 1.90% to 4.57%. This method allowed for measurement of the concentrations of lignans and tocopherols in six commercial sesame oils. This technique is simple, accurate, and highly sensitive and can therefore be used for the routine analysis of real samples.

Abstract Flood is the devastating natural events as it causes massive destructive of life, economy and infrastructure. The main objective of this study was flood inundation mapping using HEC-RAS model; the case of Awash Bello flood plain, Upper Awash River basin, Ethiopia. River geometry, annual peak flood, and boundary conditions are the most important input parameters for RAS preprocessing. River geometry such as river center line, left and right bank line, flow path line, and XS Cut line were extracted from DEM of the Awash Bello flood plain with aid of the Arc GIS and HEC-RAS interface called HEC-Geo RAS and exported to HEC-RAS for the completion of RAS preprocessing. Annual peak flood frequency analysis for different recurrence interval (i.e. 2,5,10,25,50, and 100-years) were computed using the calibrated and validated HEC-HMS model based on a 25 years (1990-2015) hydro-meteorological data collected from Ministry of Water Resources Irrigation and Electricity and National Meteorological Agency respectively. The model result depicted the flood extreme value for the respective recurrence interval were 526,610,828.8,1072.8,1263.6, and 1461.3 m3/s respectively. For more reliability, the HEC-HMS model outputs were compared with the flood extreme value obtained from Log-Pearson type III, General Pareto and Gumbel extreme value distribution function and it was found the HEC-HMS model result for every recurrence interval were higher than the extreme value distribution function outputs. After verifying the acceptability of the HEC-HMS model result, the verified peak flood was inserted into HEC-RAS model and flood inundation mapping for different recurrence interval were executed. The HEC-RAS model outcome indicated that the flood inundation mapping area for 2,5,10,25,50, and 100-year recurrence interval respectively were 71.475,76.630,89.150,100.290,105.160, and 109.462km2. Finally, it was realized that the whole Awash Bello flood plain is under the influence of flood inundation due to the intensive rainfall event. Key Words: Awash Bello, DEM, Flood Frequency Analysis, Flood Inundation Mapping, HEC-HMS, HEC-RAS, HEC-Geo RAS, Arc GIS,

Background: Traumatic optic neuropathy (TON) can be caused by direct or indirect injury. Direct optic injury usually results from optic nerve avulsion or laceration, or from direct fracture of the optic canal. Indirect optic injury is caused by increased intracanalicular pressure after an injury. The prognosis of direct optic injury is usually quite poor. To date, no standardized treatment protocol has been developed for TON. In this study we are assessing the visual improvement in patients with direct TON who underwent endoscopic optic nerve decompression in the last 10 years. Methods: 32 cases of optic nerve decompression for direct TON were done in the last 10 years. Preoperative and post operative visual assessment were done and followed up for 3 months, Results: There was complete improvement in vision in 59% of patients when optic nerve decompression was done within 72 hours of trauma; whereas 31% cases had partial improvement when done between 3 and 7 days. And there was 0% improvement when done after 7 days. Conclusion: Endoscopic optic nerve decompression is a minimally invasive effective method in direct traumatic optic neuropathy with minimal or no complications when done by well experienced ENT surgeon with ample knowledge of anatomy and anatomical variations. Other important prognostic factors include timing of surgery, extend of trauma and preoperative visual status Key words: Endoscopic optic nerve decompression (EOND), Nerve sheah incision/ fenestration, Traumatic optic neuropathy (TON), Visual assessment( VA), Visual improvement scale (VIS)

Introduction: Studies have shown an association between outcome in cardiac resynchronization therapy (CRT) and longer interventricular delay at the site of the left ventricular (LV) lead. Targeted LV lead placement at the latest electrically activated segment increases LV function further as compared with standard treatment. We aimed to determine reproducibility and repeatability of identifying latest electrically activated segment during mapping of all available CS branches in patients receiving CRT. Methods: We included 35 patients who underwent CRT implantation with protocolled mapping guided LV lead implantation aiming for the site of latest electrical activation. Three different doctors experienced in electrophysiology and implantation of CRT devices independently measured time interval from the local bipolar right ventricular (RV) electrogram (EGM) to the local unipolar LV EGM at all mapped sites (RV-LV). The segment with the latest electrical activation was defined as target segment (TS) and the CS tributary containing TS was defined as target vein (TV). Weighted Kappa statistics with 95% confidence intervals were computed to assess intra-and inter-observer agreement for TS and TV. Results: We mapped 258 segments within 131 veins. Weighted kappa values for repeatability were 0.85 (0.81-0.89) for TS and 0.92 (0.89-0.93) for TV, and weighted kappa values of inter-observer agreement ranged from 0.70 (0.61-0.73) to 0.80 (0.76-0.83) for TS and 0.73 (0.64-0.78) to 0.86 (0.83-0.89) for TV among all three observers. Conclusion: The reproducibility and repeatability of identifying latest electrically activated segment during mapping of all available CS branches in patients receiving CRT ranges from good to very good.

Contagious ecthyma is a zoonotic disease caused by the Parapoxvirus virus, Orf (ORFV) affecting sheep, goats, humans and is widely distributed across the world, including India. Here, we have investigated the 2017 ORFV outbreak in goats that occurred in the central Indian state of Madhya Pradesh. The outbreak was characterized by a moderate rate of morbidity (up to 20%) with no mortality. Phylogenetic analysis of four partial genes, such as ORFV011, ORFV020, ORFV059, and ORFV108, revealed the transboundary potential of the virus by showing its relationship with a distinct geographical area. We characterized the complete genome of this strain named Ind/MP and performed comparative genomic analysis. The Ind/MP whole genome consists of 139,807 bp with GC content 63.7%. The genome contains 132 potential open reading frames (ORFs) flanked by inverted terminal repeats (ITRs) of 3,910 bp at both ends having terminal BamHI sites and conserved telomere resolution sequences. Population genetic parameters such as nucleotide diversity (π), selection pressure analysis (θ=dN/dS), etc. suggest that the ORFV resides under purifying selection. The potent molecular markers, such as Simple Sequence Repeats (SSRs) and compound SSRs (cSSRs) were more prevalent within the functional protein with the value 70% and 67%, respectively. A total number of forty recombination events were identified, out of which Ind/MP strain actively participate in twenty-one events suggesting that this strain can recombine for the generation of new variants.

Acute heart failure (AHF) is a common clinical emergency characterized by pulmonary edema, with rapid progression and poor prognosis. In the past, clinicians mostly used physical examination, chest radiography (CXR) and brain-type natriuretic peptide (BNP) for diagnosis and evaluation of the treatment effects of AHF, but their application is limited due to the long duration and low sensitivity and specificity. Recently, lung ultrasound (LUS) is found to be a simple, fast and effective approach to detect pulmonary edema and diagnose AHF. Here we aimed to provide a review on the use of LUS in management of AHF, which focused on the application of LUS in diagnosis, treatment and prognosis of AHF

Objective: To investigate HCQ interaction mechanistic under COVID-19 with and without pro-arrhythmic comorbidities such as Long QT syndrome (LQTS1 & 2), and hypokalemia in (a) three types of cardiomyocytes (b) ventricular tissue and its effects when excited with premature beats (PBs) to understand the possibility of arrhythmogenesis. Methods and Results: A 2D transmural anisotropic ventricular tissue model consisting of endocardial, mid myocardial and epicardial myocytes are configured for mild and severe COVID-19, comorbid, and HCQ conditions. Results show that along with QT interval reduction, low amplitude and/or inversion T-wave occurred in mild and severe COVID-19 respectively. In contrast, under LQTS1 and mild hypokalemia leads to notched T-waves, and HCQ inclusion increases the QT interval and T-peak in all mild infections. Severe COVID-19 causes inverted T-waves and shorten QT-interval in all comorbidities except in LQTS2, where biphasic T-waves are observed. Arrhythmogenesis, reentry is created only on the addition of mild hypokalemia while ST elevation is observed in the presence of moderate and severe hypokalemia. When treated with HCQ, no significant impact occurred. Conclusion: In-silico ventricular model indicates, HCQ has an insignificant effect on COVID-19 without and with comorbidities, except in the combination of mild COVID-19 with moderate hypokalemia condition and severe COVID-19 with mild hypokalemia where it initiated a re-entrant arrhythmia. These results could help guide COVID-19 management

Objectives. We compared the common pathway components C3a, C5a and membrane attack complex (MAC), also known as C5b-9, and the alternative pathway components factor B and properdin in patients with ANCA-associated vasculitis (AAV) and healthy controls, and conducted a meta-analysis of the available clinical evidence for the role of complement activation in the pathogenesis of AAV. Methods. Complement components were evaluated in 59 patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis and 36 healthy volunteers. In 28 patients, testing was repeated in remission. Next, we performed a meta-analysis by searching databases to identify studies comparing complement levels in AAV patients and controls. A random-effects model was used for statistical analyses. Results. The median concentrations of MAC, C5a, C3a, and factor B were higher in active AAV patients (p<0.001). Achievement of remission was associated with reductions in C3a (p=0.005), C5a (p=0.035), and factor B levels (p=0.045), whereas MAC and properdin levels did not change. In active AAV, there were no effects of ANCA specificity, disease phenotype, previous immunosuppression, or disease severity on complement levels. A total of 1122 articles were screened, and five studies, including this report, were entered in the meta-analysis. Plasma MAC, C5a, and factor B in patients with active AAV were increased compared to patients in remission (excluding factor B) and controls. Changes in C3a were of borderline significance. Conclusion. Our findings and the results of the meta-analysis support activation of the complement system predominantly via the alternative pathway in AAV patients.

Variations in immune responses could define successful resistance to Hepatitis C Virus (HCV) infection. Toll-like receptors (TLR)-3 are innate detectors of dsRNA viruses while TLR9 recognizes bacterial and viral unmethylated CpG motifs. We previously reported that TLR3.rs3775290 “CC” genotype was associated with HCV chronicity, while TLR9 gene played no major role in this infection. This study identified the role of TLR3.rs3775290 (c.1377C/T), TLR9.rs5743836 (-1237T→C) and TLR9.rs352140 (G2848A) gene polymorphisms in predicting the outcome of HCV-specific cell-mediated immunity (CMI) among Egyptian healthcare workers (HCWs) and patients. We enrolled 546 subjects (409 HCWs and 137 patients) divided into four groups. Group1: 265 seronegative, aviraemic subjects; group2: 25 seronegative, viraemic subjects; group3: 87 subjects with spontaneously resolved HCV infection; and group4: 169 chronic HCV HCWs and patients. All subjects were genotyped for TLR3.rs3775290, TLR9.rs5743836 and TLR9.rs352140 SNPs by PCR-restriction fragment length polymorphism (PCR-RFLP) analysis. We, also, quantified HCV-specific CMI in 265 HCWs distributed among the four groups using an interferon gamma (IFN-γ) enzyme-linked immunospot (ELISpot) assay in response to nine HCV genotype 4a overlapping 15mer peptide pools covering the whole viral genome. No statistically significant difference was found between CMI responding subjects among Egyptian HCWs with different HCV states and TLR3.rs3775290 genotype or TLR9.rs352140. However, there was a significant relationship between the outcome of the HCV-specific CMI and the TLR9.rs5743836 genotype among the responding subjects (p=0.005) and the chronic HCV patients (p=0.044). In conclusion, TLR9.rs5743836 SNP; but not TLR3.rs3775290 or TLR9.rs352140 genotypes; could predict the outcome of HCV-specific CMI responses among genotype-4-infected Egyptians.

The branded pharmaceutical industry is a slow innovation industry, because of the long time to market of new molecular entities (NME). On average, it takes ~10-15 years from concept to product, at a cost of ~$1-5 billion, and a failure rate of ~90% [1]. There are generally two reasons why the timelines are long. One involves the linear phase sequencing of clinical trials and the other, is around financial risks around probability of technical and regulatory success. A perhaps more proximal issue is that pharmaceutical R&D enterprises are organized around prioritized investments, working on assets with the greatest return of investments. There is much less appreciation or flexibility in leveraging expertise around priorities that are often thrust on the system by external forces, such as the current pandemic. Addressing emerging public health concerns, including preparedness for epidemic/pandemic situations, requires a hypervelocity mindset, which the current apparatus is least prepared for. This commentary offers insight into the organizational preparedness into mobilizing resources and scientific creativity for accelerated timelines in response to pandemics.

Background: Ever since the COVID-19 pneumonia emerged in Wuhan, China, in December 2019, it has rapidly spread worldwide, resulting in high mortality. This study aimed to delineate the clinical characteristics of critically ill patients with COVID-19 infection in the intensive care unit. Methods: In this retrospective study, the clinical characteristics of 88 critically ill patients with COVID-19 infection were collected. Analysis among three subgroups, classified according to the survival time, was performed. Results: The median age was 70.7(62.3-78.25) years of critical ill patients. Hypertension (43.2%) was the most frequent underlying disease. At the time of admission, compared to other patients, patients of the≤7 days category showed greater impairment of consciousness, as per the Glasgow Coma Scale (GCS) scores(11.0±2.9, P<0.01). The lymphocyte percentages in all patients (4.1 ± 0.78) were much lower than the normal values. Particularly, acute kidney failure occurred more frequently in patients of the ≤7 days category (45.2%, P<0.01). The time distributions of the mortality rates were 31deaths in ≤7 days, 33 deaths in 8–14days, and7 deaths in >14days (P=0.01). Conclusion: Critically ill patients with COVID-19 infection showed high risk of mortality. The primary immune response of lymphocytes against the COVID-19 infection was severely destroyed. Higher GCS score predicted greater possibility of survival. However, acute kidney injury may be an indicator of worse outcome.

Effective Cervical screening involves a complex sequence of interactions between women, clinical staff and systems. Even in well organised screening programmes, achieving high population coverage is challenging. The transition to using Human Papilloma Virus (HPV) testing as the primary screening modality, rather than cytology, has introduced the possibility of using a self-collected sample for the primary HPV test. This has been shown to be a reliable method of detecting CIN2+ (Polman et al, Lancet Oncology 2019;20(2):229-38).Regardless of the way the sample is collected, the low specificity of a positive HPV test means that positive results must be triaged. In all cases where self-sampling has been integrated into a cervical screening programme to date, this triage is by cytology on a subsequent, clinician taken sample. Other molecular tests which can be performed on the original sample may in the future be an alternative, but are not yet fully evaluated.It has generally been assumed that a self-collected sample would not be suitable for cytology because the cervix is unlikely to be thoroughly (if at all) sampled.However, the authors have shown that using a well-established self-sampling device, 95.8% samples had at least 5000 cells, the usual threshold for adequacy for cytology. (ThinPrep LBC method). Results were highly specific, and in fact the positive predictive value (PPV) for high grade disease was higher on the self-collected specimens than on the subsequent professionally taken samples (Loopik et al. BJOG 2020 xxxx).As expected, the sensitivity of the test was lower than for a professionally taken sample, but it still detected 29.4 % of CIN2+. In this study, an impressive 91.9% of women returned for their reflex cytology test. This is higher than in other studies, possibly because the study was not focussed on women who have previously not responded to invitation.It is likely that a significant proportion of women needing treatment could be reliably identified by self-sampling alone by this method.It is worth noting that despite implementation in several organised screening programmes, self-sampling tests for HPV have yet to achieve regulatory approval, and the process for doing so for cytology from self-collected samples is likely to require studies with more extended monitoring of clinical outcomes.Self-sampling is not yet widely implemented internationally and the pathways can be challenging. There is a concern about how to address loss to follow up, design of multistep pathways for management, and potential delays in diagnosis. A pathway which could reliably prioritise women for referral for immediate colposcopy, with a high PPV for CIN2+, without requiring a face to face clinical interaction would be extremely valuable. This is potentially even more topical in the post COVID-19 world where there are new challenges in risks of consultations and in capacity of health care delivery.No disclosures: A completed disclosure of interest form is available to view online as supporting information.

Background and Purpose: SARS-coV-2 pandemic continues to cause an unprecedented global destabilization. There is an urgent need to develop vaccines or identify molecules to treat severe cases and repurposing of drugs is the best approach at this hour. Thalidomide, despite having an infamous history has been successfully repurposed and tested for various disease conditions including inflammatory diseases and tumor. Few reports emphasize the use of thalidomide with a SARS-coV-2 pneumonia patient being successfully treated with thalidomide. Experimental Approach: A meta-analysis comparing the transcriptomes of SARS-coV-2 infected tissues with thalidomide and lenalidomide-induced transcriptomic changes in transformed lung, endothelial and hematopoietic models was performed. Key Results: Thalidomide and lenalidomide exhibited pleiotropic effects affecting a range of biological processes including inflammation, immune response, angiogenesis, MAPK signaling, NOD-like receptor signaling, TLR signaling, leukocyte differentiation and innate immunity, the processes which are aberrantly regulated in severe COVID-19 patients. In addition, we show the similarities between the expression profiles of SARS-coV-2 infected lung and systemic lupus erythematous. Conclusion and Implications: The present study recommends thalidomide analogs as a “better fit” to treat severe cases of novel viral infections, healing the damaged network by compensating the impairment caused by the Coronavirus disease-2019 (COVID-19).

The effect of abscisic acid (ABA) to increase the osmotolerance of the freshwater microalga Chlamydomonas reinhardtii at its different stages of life cycle was investigated. Exogenously added ABA enhanced the growth and photosynthesis of C. reinhardtii during the vegetative stage. The hormone also increased the tolerance of this alga to oxidative stress during gamete formation under nutrient depletion and high salinity, as it supported their survival for a longer period. We show that the level of reactive oxygen species (ROS) generated in the ABA-treated cells was significantly less than that in the untreated cells under inhibiting NaCl concentrations. Cell size examination showed that ABA prevents cells from forming palmella when exposed to high salinity. All together, these results suggest that ABA increases the tolerance of C. reinhardtii to salt stress conditions.

For more than a century, despite numerous documented therapeutic effects, extraction, administration and studies on propolis have all been focusing mostly on its phenolic compounds. However, some important components may have gone unnoticed and this perhaps has been preventing the exploitation of the full efficacy of the substance in the treatment of human infections/diseases. In the scientific literature there are already consistent clues that propolis main components, responsible for its medicinal properties, are, actually, antimicrobial peptides (AMPs). To investigate this possible existence of AMPs in propolis, experiments that can be easily reproduced were developed and, beyond not allowing the rejection of the hypothesis, may have revealed extraordinary evidence that the substance has a large amount of cationic AMPs, which produce strong effects. It was found that propolis, differently from the effects produced only by its phenolic compounds, has, given the significant hydrophobic residues of the water-soluble cationic peptides that abound in it, strong amphipathic/surfactant (detergent-like) character and its therapeutic mechanism of action is physical/structural, through electrostatic force. In order to produce effects, the cationic peptides in propolis bind, by attraction, to anionic moieties of the organism/agent with which the substance interacts, and generate a cascade of phenomena. Thus, the results of the experiments developed suggest that there is a potential that should be extensively explored by science; i.e., propolis and its cationic AMPs possibly have strong antimicrobial and disease fighting properties and are designed to not be resisted by any pathogen, mainly if applied directly to the infection/disease site in the necessary amount. The experiments may also have revealed, as studies have been demonstrating that propolis is non-toxic and safe to be used by humans even in large doses, a possible powerful therapeutic agent that is ready to be utilized now against SARS-CoV-2. Propolis existing extracts may be easily tested for effectiveness and their use for prophylaxis or treatment of COVID-19 may be quite simple given that the substance, as demonstrated, seems to be basically a more complex and selective/non-toxic “detergent/soap” that humans have been safely using internally. Inhalation of extracts may be highly effective and the best existing way for propolis parenteral administration, enhancing the absorption and systemic effects; it may also allow direct action against SARS-CoV-2 in the respiratory tract – possible prompt binding of the positively charged AMPs from propolis to all negatively charged parts of the viruses/host’s cells and their products/substances, potentially annihilating the virus and producing immunomodulatory effects. In conclusion, propolis may be able to bring together, in the same substance, the expected effects of various therapeutic agents, and, as a result, it is possibly a viable and promising treatment alternative for COVID-19, especially in comparison with the traditional drugs being tested at the moment. Through the present study it was demonstrated as well that propolis has sufficient preclinical proof and safety to be tested in humans; therefore, considering the current pandemic, it is suggested that further studies on the substance should start urgently, primarily clinical trials on its possible efficacy in the treatment of COVID-19.

We present a 37-year-old man with history of incompletely treated testicular germ cell tumor presenting with persistent cough. Computed tomography(CT) demonstrated a large pulmonary mass invading the mediastinal vasculature, bronchi, and thrombus in the pulmonary vein extending into the left atrium. Biopsy of the lung mass confirmed germ cell tumor. Transthoracic echocardiography revealed a mass in the left atrium, consistent with a tumor or thrombus. Systemic chemotherapy was started with cisplatin and etoposide with curative intent.

Rapid evolution of traits and of plasticity may enable adaptation to climate change, yet solid experimental evidence under natural conditions is scarce. Here, we imposed rainfall manipulations (+30%, control, -30%) for ten years on entire natural plant communities in two Eastern Mediterranean sites. Additional sites along a natural rainfall gradient and selection analyses in a greenhouse assessed whether potential responses were adaptive. In both sites, our annual target species Biscutella didyma consistently evolved earlier phenology and higher reproductive allocation under drought. Multiple arguments suggest that this response was adaptive: it aligned with theory, corresponding trait shifts along the natural rainfall gradient, and selection analyses under differential watering in the greenhouse. However, another seven candidate traits did not evolve, and there was little support for evolution of plasticity. Our results provide compelling evidence for rapid adaptive evolution under climate change. Yet, several non-evolving traits may indicate potential constraints to full adaptation.

Foraging based on prey elemental content could be more pronounced if consumers leveraged differences in physical traits among stoichiometrically distinct prey to ingest more favorable food, allowing consumers to meet their threshold elemental ratios (TER). We offered the marine copepod, Acartia tonsa, different combinations of large and small diatom congeners, grown to be either stoichiometrically replete or nitrogen-deficient. When offered each diatom alone, A. tonsa exhibited compensatory grazing on large diatoms, and ingested more nitrogen-deficient cells. When offered diatoms that differed in both size and stoichiometry, copepods mixed their diets to achieve a C:N close to their independently estimated optimal TER. When offered pairs of different-sized diatoms of similar stoichiometry, A. tonsa preferred larger cells, suggesting evolutionary constraints drive choice when stoichiometric differences are minimal. Experiments describing selectivity on single traits may seriously underestimate how precisely copepods can optimize their dietary stoichiometry when feeding on a diverse natural prey assemblage.

Aim: Pharmacovigilance data are primarily used to identify adverse drug reactions. However, scanning for associations of drugs and adverse events that occur less frequently than expected provides hypotheses for drug repurposing, i.e. a known drug could be therapeutically beneficial for a new indication like the coronavirus disease (COVID-19). Methods: Drugs associated with viral respiratory tract infections and/or influenza were extracted from the U.S. FAERS pharmacovigilance data using OpenVigil2.1-MedDRA17, filtered for significant inverse associations (punadj<0.05), checked for plausibility, and categorised by their WHO Anatomical Therapeutic Chemical (ATC) classification code. Results: ATC clustering of 82 candidate drugs revealed anti-diabetics, neuropharmacologic sigma-receptor agonists, peptidase inhibitors, kinase inhibitors and anti-androgens. Chloroquine appears as a statistically significant risk factor for viral diseases supporting actual knowledge. Conclusion: OpenVigil 2 delivers new hypotheses for drug repurposing, theoretically for all indications. There is affirmative data for some of our results; the remaining proposed candidate drugs without already known antiviral mechanism of action should stimulate further exploration.

This study explores the relation between biomass-specific succinic acid (SA) production rate and specific growth rate of an engineered industrial strain of Saccharomyces cerevisiae, with the aim to investigate the extent to which growth and product formation can be uncoupled. Ammonium-limited aerobic chemostat and retentostat cultures were grown at different specific growth rates under industrially relevant conditions, i.e., at a culture pH of 3 and with sparging of a 1:1 CO2-air mixture. Biomass-specific SA production rates decreased asymptotically with decreasing growth rate. At near-zero growth rates, the engineered strain maintained a stable biomass-specific SA production rate for over 500 h, with a SA yield on glucose of 0.61 mol.mol-1. These results demonstrate that uncoupling of growth and SA production could indeed be achieved. A linear relation between biomass-specific SA production rate and glucose consumption rate indicated a coupling of SA production rate and the flux through primary metabolism. The low culture pH resulted in an increased death rate, which was lowest at near-zero growth rates. Nevertheless, a significant amount of non-viable biomass accumulated in the retentostat cultures, thus underlining the importance of improving low-pH tolerance in further strain development for industrial SA production with S. cerevisiae.

Although the Janzen-Connell model recognizes high level of predation as the main factor influencing propagule survival close to parent trees, acorns of white oak species germinate immediately after seed fall and might serve as a mechanism to escape this predation. In this study, we investigated the seedling establishment, growth, mortality and recruitment of two co-occurring oak species Quercus variabilis and Q. aliena as a function of distances to conspecific adults, to examine if Janzen-Connell effects necessarily result in Janzen-Connell pattern in temperate white oak forests. Our results showed that the survivorship of 1-year-old seedlings of the two white oak species was negatively correlated with the distances from the parent trees. This pattern of seedling survivorship can largely be explained by rapid germination of white oak acorns in autumn and/or the high regeneration capacity of the robust taproots even after the cotyledons are predated. Recruitment possibility indicated by the 2-year-old seedlings, however, showed an exact compensation pattern, generally reflecting the interaction between high level of seedling establishment and host-specific herbivores under the parent trees. Our results provide evidence that rapid autumn germination of acorns and high regeneration capacity of taproots limit the occurrence of Janzen-Connell effects on seedling survival close to parent trees of white oaks in temperate forests.

Dear Editor,We read with interest the published article by Ikeda et al. [1], they performed thoracic endovascular aortic repair (TEVAR) in a patient with Marfan syndrome (MFS) for acute complicated type B aortic dissection (TBAD) during COVID-19 pandemic.The evidence around TEVAR for MFS is scarce and open repair remains the gold treatment[2]. During the COVID-19 pandemic, many patients are either being denied treatment or given inferior options on the basis of age, comorbidities and risk of COVID pneumonia; however, the guidelines for aortic intervention in the United Kingdom have remained largely unchanged from pre-COVID-19 era [3]. Our questions to the authors relate to whether their solution was an unnecessary compromise. There is no clear indication defined in their case as a cold leg doesn’t necessary means an ischaemic limb. The TEVAR procedure performed aiming to minimise hospital stay, yet this approach may have put the patient at higher risk of developing paraplegia and visceral organ malperfusion, while compromising her long-term care.There is need to clarify if she had risk factors that prone her to a higher risk acquiring severe COVID-19 which necessitated deviating from the traditional open surgery recommended for MFS patients with TBAD [2]. The authors did not report on renal function, evidence of bowel malperfusion or whether there was resistant hypertension that needed immediate intervention. If the need to expediate intervention was the fear of limb ischaemia, is it conceivable a femoro-femoral bypass could have saved the limb and definitive open surgery on her aorta could have been performed at a later stage, especially since she was haemodynamically stable.Moreover, as Marfan-diseased aortas are prone to further dilatation, we believe their justification for opting for endovascular repair should also have been more balanced, exploring the know high rate of long-term TEVAR-associated complications in MFS patients including endoleaks, retrograde dissection, stent-graft-induced new entry tears, surgical conversions and reintervention. There is also need for imaging follow-up to assess the success of TEVAR and early detection of aforementioned complications.