The oleaginous yeast Yarrowia lipolytica is an important industrial microorganism used for the production of lipids, proteins and various chemicals. The design of effective biotechnological processes with this cell factory requires an in-depth knowledge of its metabolism. Here we present a transcriptomic study of Y. lipolytica grown in the presence of two important carbon sources, namely glycerol and glucose, as well as in a mixture of both at different carbon to nitrogen ratios. It emerged that the transcriptomic landscape of Y. lipolytica is more sensitive to the nitrogen availability than to the utilized carbon source, as evidenced by more genes being differentially expressed in lower carbon to nitrogen ratio. In particular, expression of hexokinase (HXK1) is significantly susceptible to changes in nitrogen concentrations. Moreover, high HXK1 expression in low nitrogen seems to impact the expression of other genes which are implicated in tricarboxylic acid cycle and erythritol biosynthesis. We further show that expression of HXK1 and two genes belonging to the sugar porter family might be controlled by GATA-like zinc-finger proteins.

1. Fire and frost represent two major hurdles for the persistence of trees in open grassy biomes and have both been proposed as drivers of grassland-forest boundaries in Africa. 2. We assess the response of young tree seedlings, which represent a vulnerable stage in tree recruitment, to traumatic fire and frost disturbances. 3. In a greenhouse experiment, we investigated how seedling traits predicted survival and resprouting ability in response to fire vs frost; we characterised survival strategies of seedlings in response to the two disturbances, and we documented how the architecture of surviving seedlings is affected by fire vs frost injury. 4. Survival rates were similar under both treatments. However, different species displayed different levels of sensitivity to fire and frost. Seedling survival was higher for older seedlings and seedlings with more basal leaves. Survivors of a fire event lost more biomass than the survivors of a frost event. However, the architecture of recovered fire and frost treated seedlings were mostly similar. Seedlings that recovered from fire and frost treatments were often shorter than those that had not been exposed to any disturbance, with multiple thin branches, which may increase vulnerability to the next frost or fire event. 5. Synthesis. Fire caused more severe aboveground damage compared to frost, suggesting that trees in these open grassland systems may be subjected to a seedling release bottleneck maintained by fire. However, the woody species composition will almost certainly be influenced by phenomena that affect the timing and frequency of seedling exposure to damage, as mortality was found to be dependent on seedling age. Therefore, changes in fire regime and climate (esp. changes that bring about less frost and reduced fire intensity and frequency) are likely to result in changes in the composition and the structure of the woody components of these systems.

The whitefly Bemisia tabaci is a closely related group of > 35 cryptic species that feed on the phloem sap of a broad range of host plants. Species in the complex differ in their host-range breadth, but the mechanisms involved remain poorly understood. We investigated, therefore, how six different B. tabaci species cope with the environmental unpredictability presented by a set of four common and novel host plants. Behavioural studies indicated large differences in performances on the four hosts and putative specialization of one of the species to cassava plants. Transcriptomic analyses revealed two main insights. First, a large set of genes involved in metabolism (> 85%) showed differences in expression between the six species, and each species could be characterized by its own unique expression pattern of metabolic genes. However, within species, these genes were constitutively expressed, with a low level of environmental responsiveness (i.e., to host change). Second, within each species, sets of genes mainly associated with the super-pathways “environmental information processing” and “organismal systems”, responded to the host switching events. These included genes encoding for proteins involved in sugar homeostasis, signal transduction, membrane transport and immune, endocrine, sensory and digestive responses. Our findings suggested that the six B. tabaci species can be divided into four performance/transcriptomic “Types” and that polyphagy can be achieved in multiple ways. However, polyphagy level is determined by the specific identity of the metabolic genes/pathways that are enriched and overexpressed in each species (the species’ individual metabolic “tool kit”).

The hot deformation characteristics of Nickel-based corrosion resistant alloy was studied in the temperature range of 1050~1200oC and the strain rate range of 0.001~0.1s-1 by employing hot compression tests. The results show that the peak stress increases with decreasing temperature and increasing strain rate, and the activation energy is about 409kJ/mol. Basing on the Avrami equation through using the critical strain (εc) and the strain for 50% DRX (ε0.5), a kinetic model for dynamic recrystallization (DRX) was established, where the model parameters could be obtained using the modified Zener-Hollomon parameter (Z*). Applying the model, the predicted value of the steady state strain (εss) and the strain for maximum softening rate (εm) agree well with the experimental results. Accordingly, the relationship between ε m and ε 0.5 is established, which is mainly dependent on the Avrami exponent (n). When n <3.25, εm becomes less than ε0.5 and the difference in between decreases with increasing the strain rate or decreasing the deformation temperature. Finally, through observing DRX microstructure under different deformation conditions, a power law relation between DRX grain size (Ddrx) and Z*, with an exponent of -0.36, was found.

Introduction: The term growth hormone secretagogues (GHS) encompasses compounds that were developed to increase growth release of growth hormone (GH). GHSs include growth hormone receptor secretagogue agonists (GHS-R), whose natural ligand is ghrelin, and growth hormone releasing hormone (GHRH) agonists, to which GHRH binds as a native ligand. In the context of selective androgen receptor modulators (SARM), the presence of a Toll-IL-1 receptor domain (TIR) predicts a role for SARMs in innate immunity. SARMs are an emerging class of therapies aimed at cachexia, sarcopenia and hypogonadism or treatment of stress urinary incontinence, osteoporosis, breast cancer and Duchenne muscular dystrophy. Objective: To present the state-of-the-art scientific evidence in humans on the use of growth hormone secretagogues, SARM and antagonists. Methods: Experimental and clinical studies were included (case reports, retrospective, prospective, randomized studies and systematic review) with qualitative and/or quantitative analysis. For further specifications, the description “Clinical Trail” for refinement was added during the research, following the rules of the systematic review-PRISMA. Of 384 articles, a total of 80 articles were evaluated in full and 58 were included and discussed in this study. Results and conclusion: Several clinical trials have been conducted and completed to assess the safety and efficacy of GHS for the diagnosis and / or treatment of GH deficiency. Over the past two decades, scientists' efforts have focused on the discovery and biological characterization of new tissue-specific SARM to promote the beneficial effects of androgens with greatly reduced undesirable side effects. In this regard, numerous studies with SARM of different structures have been reported. Despite evidenced clinical and preclinical studies, no SARM has yet received full clinical approval. Keywords: Growth hormone secretagogues. Peptides. SARM. Antagonists. Clinical Studies. 

Objective: To determine the clinical usefulness of the soluble endoglin (sEng) and uterine artery Doppler ultrasonography as markers of progression to preeclampsia in women with gestational hypertension (GH). Design: Nested case-control study. Setting: Mexico City, Mexico. Population or sample: 77 singleton pregnant women with GH. Methods: Cases were women who progress to preeclampsia (n=36) and controls were those who did not (n=41). Serum sEng concentrations and uterine artery Doppler ultrasonography were performed at enrollment. Main outcome measures: Progression to preeclampsia and occurrence of adverse outcomes, such as preterm delivery (PD) <37 and <34 weeks of gestation, small-for-gestational-age (SGA) infant, and fetal growth restriction (FGR). Results: Women with sEng values in the highest tertile had higher risk of progression to preeclampsia, PD<34 weeks of gestation, and FGR, odds ratios (ORs) ≥ 3.7. Patients with abnormal uterine artery Doppler pulsatility index (>95th percentile) had higher risk of progression to preeclampsia, PD <34 weeks of gestation, SGA infant, and FGR (ORs ≥ 3.3). The presence of notch was associated with higher risk of progression to preeclampsia, PD <37 and <34 weeks of gestation, SGA infant, and FGR (ORs ≥ 2.9). However, logistic regression analysis revealed that only serum sEng was a significant and independent risk factor for progression of GH to preeclampsia, PD <34 weeks of gestation, and FGR (ORs ≥3.1). Conclusions: sEng is a reliable biomarker of progression to preeclampsia, PD and FGR in patients with GH. Compared to sEng, uterine artery Doppler ultrasound has limited clinical usefulness as marker.

Background: Atrial fibrillation is the most common complication after cardiac surgery and is associated with an increased risk of postoperative adverse events. The objective of this study was to develop a risk index to predict atrial fibrillation after cardiac surgery. Methods: We performed a prospective cohort study. A total of 405 patients who had undergone adult cardiac surgery from 2015 September to 2016 August at Heart Institute of HCMC and Cho Ray Hospital. Results: In the overall, 98 patients developed POAF (24.2%). The risk score included three significant risk factors (age, left atrial diameter > 41mm, Coronary Artery Bypass Graft with concomitant mitral valve replacement or repair). The point values for were 1 for the age  60, 1 for CABG with concomitant mitral valve replacement or repair and 1 for left atrial diameter > 41mm, and the total risk score ranges from 0 to 3 (AUC = 0.69, 95% CI: 0.63 – 0.75), the best cutoff point was 1 The incidences of POAF associated with scores were: patient with a score of 0, predicted probabilities of POAF was 8.6%; a score of 1: 30.1%; a score of 2: 40.8%; a score of 3: 58.3%. Bootstrapping with 5,000 samples confirmed the final model provided consistent predictions. Conclusions: We developed a simple risk score based on clinical variables and these variables can be collected easily before surgery. This risk score may help accurately stratifies the risk of POAF to identify patients at high risk of POAF before cardiac surgery.

COVID-19 is a global pandemic with extensive community spread in many countries. Community hospitals (CHs) have an important role to play in offloading patients from acute hospitals and providing a longer period of rehabilitation and convalescence. Patients in CHs tend to have more chronic medical issues and are older in age and are hence particularly vulnerable should COVID-19 spread in such facilities. As such measures have to be put in place to protect this group and we share the practices put in place by CHs in Singapore in response to COVID-19.

Background: Benefits of early Cystic Fibrosis (CF) detection using newborn screening (NBS) lead to widespread use in NBS programs. Since 2002, a two-stage immunoreactive trypsinogen (IRT/IRT) screening strategy has been used as CFNBS method in all public maternities in the City of Buenos Aires, Argentina. However, novel screening strategies may be more efficient. The aim of the study is to prospectively compare two CFNBS strategies, IRT/IRT and IRT/PAP (pancreatitis-associated protein). Methods: A two-year prospective study was performed. IRT was measured in dried blood samples collected 48–72 hours after birth. When IRT value was abnormal, PAP was determined, and a second visit was scheduled to obtain another sample for IRT before 25 days of life. Newborns with a positive CFNBS were referred for confirmatory sweat test. Results: There were 69,827 births in the City of Buenos Aires during the period studied; 918 (1.31%) had an abnormal IRT. A total of 207 children (22.5%) failed to return for the second IRT, but only two PAP (0.2%) were not performed. IRT/IRT was more likely to lead to a referral for sweat testing than IRT/PAP (OR 2.3 [95% CI 1.8;2.9], p<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value were: 80% and 100%, 86.5% and 82.6%, 4.04% and 4.2%, 99.84% and 100% for IRT/IRT and IRT/PAP strategies, respectively. Conclusion: The IRT/PAP strategy is more sensitive than IRT/IRT; it avoids a second appointment and the need of unnecessary sweat testing, and decreases loss to follow up in our population.

The majority of clinically approved therapeutics target membrane proteins (MPs), highlighting the need for tools to study this important category of proteins. To overcome limitations with recombinant MP expression, whole cell screening techniques have been developed that present MPs in their native conformations. Whereas many such platforms utilize adherent cells, here we introduce a novel suspension cell-based platform termed “biofloating” that enables quantitative analysis of interactions between proteins displayed on yeast and MPs expressed on mammalian cells, without need for genetic fusions. We characterize and optimize biofloating and illustrate its sensitivity advantage compared to an adherent cell-based platform (biopanning). We further demonstrate the utility of suspension cell-based approaches by iterating rounds of magnetic-activated cell sorting (MACS) selections against MP-expressing mammalian cells to enrich for a specific binder within a yeast-displayed antibody library. Overall, biofloating represents a promising new technology that can be readily integrated into protein discovery and development workflows.

Population genomics is a useful tool in the integrated pest management toolbox for elucidating population dynamics, demography, and histories of invasion. However, next-generation sequencing approaches can be hampered by low DNA input from small organisms, such as insect pests. Here, we use a restriction-site associated DNA sequencing approach combined with whole-genome amplification to assess genomic population structure of a newly described pest of canola, the diminutive canola flower midge, Contarinia brassicola. We find that whole-genome amplification prior to library preparation caused a reduction in the overall number of loci sequenced and an increase in overall sequencing depth but had no discernable impact on genotyping consistency for population genetic analysis. Clustering analyses recovered little geographic structure across the main canola production region, but differentiated several geographically disparate populations at edges of the agricultural zone. Given a lack of alternative hypotheses for this pattern, we suggest these data support alternative hosts for this species and thus our canola-centric view of this midge as a pest has limited our understanding of its biology. These results speak to the need for increased surveying effort across multiple habitats and other potential hosts within Brassicaceae, to elucidate both our ecological and evolutionary knowledge of this species as well as potential management implications.

Organisms’ size and shape profoundly influence their ecophysiological performance and evolutionary fitness, suggesting a link between morphology and diversity. We analyse global datasets of unicellular phytoplankton, major group of photosynthetic microbes with an astounding diversity of cell sizes and shapes, and explore the distribution of taxonomic diversity across different cell shapes and sizes. We find that cells of intermediate volume have the greatest shape variation, from oblate to extremely elongated forms, while small and large cells are mostly compact (e.g., spherical or cubic). Taxonomic diversity varies across cell elongation and cell volume, with both traits explaining up to 92% of its variance. It decays exponentially with cell elongation and displays a log-normal dependence on cell volume, peaking for compact, intermediate-volume cells. Our findings point to the presence of different selective pressures and constraints on the geometry of phytoplankton cells and, thus, improve our understanding of the evolutionary rules of life.

Nitrogen (N) deficiency is one of the major constraints for potato (Solanum tuberosum L.) production, due to its shallow root system and poor capabilities of N mobilization from the deeper layers of the soil. The aim of this study was to elucidate plasma membrane (PM) proteins potentially involved in the tolerance towards N deficiency. We compared the PM proteome of the two potato cultivars ‘Lambada’ and ‘Topas’, contrasting in their N deficiency response under in vitro conditions. Using mass spectrometry we identified 65 proteins, which were differentially abundant in the two cultivars when submitted to N deficiency. Amongst those, candidate proteins were selected based on their potential to be involved in N transport under deficient conditions. Two members of the aquaporin family, StPIP1;1 and StPIP1;3, were studied in more detail. By means of a yeast growth assay we showed that these proteins do not facilitate transport of ammonia. The Arabidopsis (Arabidopsis thaliana) knockout mutants AtPIP1;1 and AtPIP1;3 showed a reduced N content and accumulation of anthocyanins under N deficiency. We conclude that PIP1;1 and PIP1;3 are indirectly involved in the N uptake under N deficient conditions and contribute to an increased N deficiency tolerance.

A 26-year-old man suffered from recurrent palpitation and his 12-lead electrocardiogram documented the alternating narrow and wide complex tachycardia. Electrophysiologic study revealed the synchronous left fascicular ventricular tachycardia (LFVT) and slow-slow atrioventricular node reentry tachycardia (ss AVNRT), and both of them were ablated successfully.

Introduction: This study aimed to evaluate the extent of baseline cardiac remodeling present in patients with new-onset cardiomyopathy (CM) with and without atrial fibrillation (AF). AF concurrent with heart failure is associated with increased morbidity and mortality. There is limited research comparing the extent of cardiac remodeling present in patients with new-onset CM associated with AF (AF-CM group) to that present in patients with new-onset CM without any concomitant or antecedent dysrhythmia (CM group). Methods and Results: Patients with a left ventricular ejection fraction ≤40% without a prior history of CM were identified from our healthcare system’s electronic medical records for the period of January 1, 2012 to September 30, 2016. Those with an antecedent or concomitant diagnosis of AF comprised the AF-CM group, and those with no prior dysrhythmia comprised the CM group. The AF-CM group (n=196) was compared with the CM group (n=197). The groups were controlled for left ventricular ejection fraction. Patients in the AF-CM group had more left atrial, right atrial, and right ventricular remodeling, more advanced right ventricular systolic dysfunction, and increased severity of both tricuspid and mitral regurgitation at presentation than the CM group. Conclusion: Patients with new-onset CM with AF had greater global cardiac remodeling at presentation than those with CM not associated with AF.

Acute Type A aortic dissection (ATAAD) is a condition associated with a mortality rate up to 26% and significant morbidity. Despite advances in numerous aspects of cardiac surgery a traditional approach of ascending aorta and “hemi-arch” replacement utilising deep hypothermic circulatory arrest (DHCA) and an open distal anastomosis persists for the management of this condition in most centres. We hereby describe the rationale behind our surgical approach of the branch-first total aortic arch replacement technique for the management of ATAAD.

Introduction. The treatment of congenital complete AV block (CCAVB) is burdened by RV-associated ventricular dysfunction at long-term in a subgroup of patients. Methods and Results. Two CCAVB adolescents with mild systolic dysfunction associated to VVIR pacing reached elective pacemaker replacement after 10±1 years. They were upgraded to physiologic stimulation by restoring AV synchrony and ventricular activation via His bundle pacing (HBP). At 9-months follow-up both had reverse left ventricular (LV) remodeling: LV end-diastolic volume index decreased from 89±4 to 70±7 ml/m2, LV end-systolic volume index decreased from 49±1 to 32 ml/m2, LVEF increased from 43±1% to 53±4%. Conclusions. HBP can improve LV function in CCAVB adolescents. It should be considered in the setting of LV dysfunction associated to RV pacing, and should be explored as first-choice treatment from late childhood onward.

It has been six months since the outbreak of the Coronavirus Disease 2019 (COVID-19) and despite ongoing research efforts, much of it still remains uncertain. Since December 2019 when the infection was first identified, more than 16000 MEDLINE-indexed papers have been published surrounding this subject matter. It is of utmost importance to learn about COVID-19 infection and its potential effects on pregnancy and perinatal outcomes, in order to guide obstetrical management during this current disease outbreak. As such, many obstetric units have been expeditiously publishing data from their studies in an attempt to rapidly disseminate information on COVID-19 in pregnancy. To date, most of these publications have been in the form of case reports and case series. While these reports provide valuable information which have helped to guide early management in this rapidly evolving global pandemic, they are not ranked highly in the traditional hierarchy of evidence. [1]Case reports are known to be at risk of publication bias and may not be suitable for statistical inferences. Case series typically lack controls, and are prone to bias. Furthermore, inconsistency across reporting and small sample size, make it difficult for conclusive inferences to be drawn. This may not be representative of the larger global situation. Thus, findings from these studies may not be widely applicable to larger populations of patients.[2] As we await better quality evidence from large laboratories and population databases, current systematic reviews and management guidelines have developed their recommendations based on findings from studies done during previous disease outbreak (e.g. Severe Acute Respiratory Syndrome (SARS) Coronavirus) and personal experiences with COVID-19, in addition to the current available literature on COVID-19. This has led to discrepancies in recommendations especially in areas with scarce data. This commentary aims to highlight some of the potential problems and limitations one may encounter when reviewing the existing literature.In addition to the limitations in the study design of case reports and series, the problem of duplicate reporting needs to be addressed. Not only does duplicate reporting of the same patient overload available medical information, it also overemphasizes findings. This will in turn affect the accuracy of all subsequent data analyses and preclude valid systematic reviews. Therefore, it is of paramount importance to screen for overlapping cases before performing analysis.This process has been challenging as some studies may not have clearly indicated if their patient series includes patients who may have been included in other published papers. This is especially of concern in areas where care or isolation facilities for COVID-19 are limited and patients may transfer between hospitals resulting in such cases being reported by both the admitting and receiving hospitals. Case studies may report on different aspects of the same case, rendering efforts to screen for duplicates by direct comparison of clinical characteristics and outcomes impossible. Some investigators have unfortunately reported failed attempts of contacting the corresponding author to identify the actual source of cases.[3]A strict and rigorous system to screen for duplicates needs to be in place when performing a systematic review. Special attention should be paid to studies originating from countries with high COVID-19 related research output as risk of case duplication could be higher. Identifying the roles of the various healthcare institutions within the same country might be useful in identifying the admitting and receiving hospitals and thus, the possibility of overlapping cases. For studies derived from the same institution, direct comparison of data should be undertaken where applicable.Apart from studies done during the peak of the COVID-19 outbreak in Hubei province, where patients were diagnosed with COVID-19 based on clinical signs and symptoms, epidemiological history and typical chest computed tomography (CT) findings, all other studies included only patients with laboratory confirmed positive quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay. However, the viral nucleic acid test has a false-negative rate of up to 30%. [4] Furthermore, studies have reported asymptomatic carriers who were only incidentally picked up during universal screening.[5] This suggests that many asymptomatic cases of COVID-19 have likely been undiagnosed. Thus, current literature may have underreported the actual prevalence of COVID-19 amongst pregnant women as well as the associated COVID-19 pregnancy outcomes and complications.Conversely, as the follow-up period for these studies have been short and most patients are in their third trimester of pregnancy, there might be an overestimation of risks such as preterm birth whilst underestimating longitudinal risks such as fetal growth restriction. [6] The increased risk of preterm birth may also be confounded by the fact that some of these deliveries were expedited to optimize the maternal condition. As the indication for delivery may not always be clearly specified in case reports, it is near-impossible to extrapolate data about the rate of spontaneous versus iatrogenic preterm birth. It is important to recognise that other factors such as stress and anxiety, especially prevalent during a time of pandemic, can also have detrimental impact on perinatal outcomes. Hence, the lack of comparable controls negates attributing these complications and outcomes solely to COVID-19 infection.Existing case reports and case series mainly focus on the characteristics of COVID-19 infection in pregnant women and the potential effects on pregnancy outcomes. Information revolving other peripartum issues such as breastfeeding, possibility of vertical transmission and the need for postpartum isolation, remains relatively limited.Systematic reviews need to follow a strict study protocol with clearly stated inclusion and exclusion criteria. As a result, a large proportion of other resources such as commentaries, opinions, expert reviews, and letters to editors are typically excluded. Important clinical observations and findings based on experiences or experts’ own research regarding COVID-19 might not be captured in these reviews.Additionally, it should be highlighted that the findings of a systematic review are only accurate and updated up to the point of submission for publication. However, in the face of an evolving disease, new information and literature are emerging rapidly. Accounting for the time required for processing, findings may not always be the most updated by the time of publication. If more than 16000 papers can be published within a 6-month period, it is a massive challenge for both researchers and readers to make conclusive decisions based on a single systematic review. To date, there are at least 8 published systematic reviews on COVID-19 and pregnancy with varying conclusions. [3, 6-12]While timely reporting of findings regarding COVID-19 is necessary and crucial to supplement our understanding of the infection and thus, guide clinical management, reviewers and guideline developers should bear in mind the limitations and interpret findings with caution. At present, the conclusions drawn from the current body of evidence may be at risk of bias. Establishment of rigorously governed national and international registries can help to address some of these issues. Although it is important to recognize the limitations of these studies and reviews, we are immensely grateful for the tremendous ongoing research efforts during this challenging time of a global pandemic. The quick dissemination of information inevitably helps clinicians to keep abreast of the latest developments, thereby guiding and updating clinical management as deemed appropriate. As we continue the fight against COVID-19, we look forward to more extensive research outcomes, contributing to a higher level of evidence.

Biologics have revolutionized the treatment of inflammatory arthritis, but their impact on T cell function is unknown. We evaluated the effect of tumor necrosis factor-alpha (TNF-α), interleukin-17A (IL-17A), and IL-6 receptor (IL-6R) blockers on T cell function in psoriatic arthritis (PsA) patients. Peripheral blood mononuclear cells (PBMCs) from PsA patients (n=111) and healthy controls (n=20) were co-cultured with adalimumab (ADA), ixekizumab (IXE), tocilizumab (TCZ), or medium alone for 5 days. T cell activation and proliferation were determined by flow cytometry and cytokines in supernatants were measured by ELISA. Activated CD4+CD25+ T cells were significantly down-regulated by ADA in naïve, conventional disease-modifying anti-rheumatic drug (cDMARD)- and biologic-treated PsA patients compared to medium (p < 0.04, p < 0.01, respectively), IXE, and TCZ. In healthy, ADA reduced the activated CD4+CD25+ T cells proportion but non-significantly as compared to the other groups. Inhibition of PsA patients derived lymphocytes proliferation by the biologics was determined in response to phytohemagglutinin (PHA). The strongest ability to suppress the extent of PHA-induced proliferation was exerted by ADA (p < 0.01) compared to IXE and TCZ. IL-1β, IL-17A, and MMP-3 levels were down-regulated by ADA compared to medium (p < 0.02, p < 0.0001, p < 0.002, respectively). IXE reduced IL-17A (p < 0.0001) but not IL-1β or MMP-3 levels. TNF and IL-17A blockades are suitable for PsA treatment, but exhibit different activity on T cells. Moreover, the study reveals part of the mechanism exerted by ADA and provides a possible explanation for TCZ inefficacy in PsA.

Transient gene expression (TGE) using mammalian cells is an extensively used technology for production of antibodies and recombinant proteins and has been widely adapted by both academic and industrial labs. Chinese Hamster Ovary (CHO) cells have become one of the major work horses for TGE of recombinant antibodies due to their attractive features: post-translational modifications, adaptation to high cell densities, and use of serum-free media. In this study, we describe the optimization of parameters for TGE for antibodies from CHO cells. Through a matrix evaluation of multiple factors including inoculum, transfection conditions, amount and type of DNA used and post-transfection culture conditions, we arrived at an optimized process with higher titer and reduced costs and time, thus increasing the overall efficiency of early antibody material supply. We investigated the amount of coding DNA and the influence of size of the transfection complex on the in vitro efficiency of the transfection. Generation of the transfection complex in serum-free medium leads to the prompt formation of an optimal-sized polyplex, and is independent of the relative amount of coding DNA used for a successful transfection outcome.

Canine influenza virus (CIV) is an emerging pathogen that can infect canines, causing a series of respiratory symptoms. H3N2 CIV emerged in dogs in China and Korea in approximately 2005 but was first reported in 2007. In 2015, H3N2 CIV was detected in the USA, where it caused a large outbreak. For continuous monitoring of H3N2 CIV in China, a total of 180 dog nasal swabs were collected from veterinary hospitals in southern China between 2017 and 2018 and tested for CIV RNA. Three H3N2 CIV strains were isolated. Following genome sequencing, sequences of the isolates were found to be divergent from the sequences of reported Chinese H3N2 CIV strains. Phylogenetic analyses indicated that these viruses are clustered in a novel group and genetically close to strains from the USA. Several unique aa substitutions in HA and NA were observed in the H3N2 CIV strains isolated in this study. These findings reveal unique evolutionary characteristics of recently identified H3N2 CIV strains in China.

The biomass ratio of herbivores to producers reflects the structure of a community. Four primary factors have been proposed to affect this ratio, including production rate, defense traits, and nutrient contents of producers as well as predation by carnivores. However, the relative importance of these factors across natural communities is elusive, in part because of the lack of a framework for quantitatively comparing their effect sizes. Here, we develop a framework based on Lotka-Volterra equations for examining the relative importance among these factors in determining the biomass ratio. We further utilize it to analyze plankton communities in experimental ponds with different carnivore (fish) abundance and light input. We found that all four factors contributed significantly to the biomass ratio, but carnivore abundance had the largest effect size, followed by the stoichiometric nutrient content. The present framework is useful for quantifying relative roles of these factors shaping terrestrial and aquatic communities.

Dear Editor,COVID-19 was first reported in December, 2019 in Wuhan, China, and rapidly spread across the globe 1. It has affected more than 6.4 million people and has led to the death of over 370 thousand as of June 2, 2020 (www.who.org). Severely affected patients present fever, dry cough, dyspnea, and fatigue, which are commonly associated with the development of pneumonia and acute respiratory distress syndrome (ARDS) 2. Advanced age, ischemic and congestive heart disease, hypertension, diabetes, and chronic obstructive pulmonary disease (COPD) are the most important independent predictors of death 2,3. As with other infectious diseases affecting the respiratory tract, asthma has been cited as a potential risk factor for severe COVID-194-6; however, no previous study has addressed this specific question.Here, we systematically reviewed all papers published on COVID-19 since its emergence in December 2019 to May 18, 2020, looking into the description of asthma as a premorbid condition and its putative association with severe progression of the disease.Two authors, NFM and CPJ, independently identified cross-sectional and longitudinal studies published before May 18, 2020, that reported on the prevalence of asthma as a premorbid condition of severe COVID-19 by systematically searching PubMed-NCBI database. We restricted the search for PubMed-NCBI because COVID-19 is a new medical condition and, currently, PubMed-NCBI covers more than 90% of MEDLINE providing a widely accessible biomedical resource 7. For database searches, language of the article was restricted to English. Search terms included the following: COVID-19 (COVID, COVID 19) ornCov or novel coronavirus or Sars-Cov-2 in the title and clinical characteristics or asthma anywhere in the text. Three authors, EM, EPA, and LAV, resolved eventual discrepancies by discussion and adjudication.We found 458 articles that met the initial inclusion search criteria (Supplementary Figure 1). All articles were assessed by authors and 290 were excluded (Supplementary Table 1) due to one or more of the following criteria: editorials; metanalyses; systematic reviews; commentaries; letters to the Editor; no description of patient’s clinical characteristics or premorbid conditions; and main text in a language other than English.The remaining 150 articles were included in the study. Supplementary Table 2 depicts the details of all articles analyzed. As a whole, the articles described the clinical aspects of 36,072 COVID-19 patients. One hundred and seven studies mentioned the existence of other respiratory premorbidities except for asthma. Asthma was mentioned as a premorbid condition in only eighteen studies (Table 1). There was a total of 8,690 patients included in the studies mentioning asthma, and 655 patients were previously diagnosed with asthma. In most of the studies describing other respiratory illnesses, COPD was the leading diagnosis.Based on the current medical records, we conclude that 7.5% of patients included in articles describing the clinical characteristics of COVID-19 patients and citing asthma were previously diagnosed with asthma. If all studies providing any clinical description of COVID-19 comorbidities are taken into consideration, asthma was present in only 1.8% of patients. These numbers are far less than expected considering the prevalence of asthma in the world. According to the World Asthma Report (http://www.globalasthmareport.org), there were as many as 339 million people living with asthma in the world in 2018, which corresponds to 4.4% of the world’s population.In conclusion, asthma does not seem to be an important premorbid condition in COVID-19 patients; or, conversely, it could be a protective factor, as previously proposed 8. The findings herein reported could be an epidemiological truth that should be further explored in mechanistic studies or could be due to the fact that researchers are not properly investigating and describing the premorbidities in COVID-19 patients. Whatever the reasons, the medical community should be aware of the implications of missing the diagnosis of a potentially severe respiratory disease such as asthma that could worsen the prognosis of COVID-19 patients.Acknowledgements. NFM was supported by The São Paulo Research Foundation (grant: 2016/17810-3), and CPJ was supported by Coordination for the Improvement of Higher Education Personnel (CAPES) grant: 1744875 and 88882.434715/2019-01. EM, LAV and EPA are supported by grants from São Paulo Research Foundation (grants: 2013/07607-8 and 2020/) and Brazilian National Council of Scientific and Technological Development (CNPq).Ethics. The study does not require ethical approval because the systematic review is based on published research and the original data are anonymous.

Introduction Fractional exhaled nitric oxide (FeNO) is a simple, noninvasive measurement of airway inflammation with minimal discomfort to the patient and with results available with a few minutes. This study aimed to evaluate the cost-effectiveness of the Fractional exhaled nitric oxide in asthma. Methods A markov model was used to estimate the cost-utility of FeNO versus standard treatment (control group) an infant with mild to moderate allergic asthma. Cost data were obtained from a retrospective study on asthma from tertiary center, in Medellin, Colombia, while utilities were collected from the literature. The analysis was carried out from a societal perspective. Results The model showed that FeNO, was associated with lower total cost than SC (US $1333 vs US $1452 average cost per patient), and higher QALYs (0.93 vs. 0.92 average per patient); showing dominance. The probability that MS provides a more cost-effective use of resources compared with standard therapy exceeds 99% for all willingness to pay thresholds Conclusion FeNO was cost-effective for the hospital treatment of an infant with infant with mild to moderate allergic asthma. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.