Towards the Ictalurid Catfish Transcriptome: Generation and Analysis of 31,215 Catfish ESTs.

Background EST sequencing is one of the most efficient means for gene discovery and molecular marker development, and can be additionally utilized in both comparative genome analysis and evaluation of gene duplications. While much progress has been made in catfish genomics, large-scale EST resources have been lacking. The objectives of this project were to construct primary cDNA libraries, to conduct initial EST sequencing to generate catfish EST resources, and to obtain baseline information about highly expressed genes in various catfish organs to provide a guide for the production of normalized and subtracted cDNA libraries for large-scale transcriptome analysis in catfish. Results A total of 17 cDNA libraries were constructed including 12 from channel catfish (Ictalurus punctatus) and 5 from blue catfish (I. furcatus). A total of 31,215 ESTs, with average length of 778 bp, were generated including 20,451 from the channel catfish and 10,764 from blue catfish. Cluster analysis indicated that 73% of channel catfish and 67% of blue catfish ESTs were unique within the project. Over 53% and 50% of the channel catfish and blue catfish ESTs, respectively, had significant similarities to known genes. All ESTs have been deposited in GenBank. Evaluation of the catfish EST resources demonstrated their potential for molecular marker development, comparative genome analysis, and evaluation of ancient and recent gene duplications. Subtraction of abundantly expressed genes in a variety of catfish tissues, identified here, will allow the production of low-redundancy libraries for in-depth sequencing. Conclusion The sequencing of 31,215 ESTs from channel catfish and blue catfish has significantly increased the EST resources in catfish. The EST resources should provide the potential for microarray development, polymorphic marker identification, mapping, and comparative genome analysis

Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Free HIV self-test for identification and linkage to care of previously undetected HIV infection in men who have sex with men in England and Wales (SELPHI): an open-label, internet-based, randomised controlled trial

BACKGROUND: High levels of HIV testing in men who have sex with men remain key to reducing the incidence of HIV. We aimed to assess whether the offer of a single, free HIV self-testing kit led to increased HIV diagnoses with linkage to care. METHODS: SELPHI was an internet-based, open-label, randomised controlled trial that recruited participants via sexual and social networking sites. Eligibility criteria included being a man or trans woman (although trans women are reported separately); being resident in England or Wales, UK; being aged 16 years or older; having had anal intercourse with a man; not having a positive HIV diagnosis; and being willing to provide name, email address, date of birth, and consent to link to national HIV databases. Participants were randomly allocated (3:2) by computer-generated number sequence to receive a free HIV self-test kit (BT group) or to not receive this free kit (nBT group). Online surveys collected data at baseline, 2 weeks after enrolment (BT group only), 3 months after enrolment, and at the end of the study. The primary outcome was confirmed (linked to care) new HIV diagnosis within 3 months of enrolment, analysed by intention to treat. Those assessing the primary outcome were masked to allocation. This study is registered with the ISRCTN Clinical Trials Register, number ISRCTN20312003. FINDINGS: 10 111 participants (6049 in BT group and 4062 in nBT group) enrolled between Feb 16, 2017, and March 1, 2018. The median age of participants was 33 years (IQR 26-44 years); 9000 (89%) participants were White; 8118 (80%) participants were born in the UK; 81 (1%) participants were transgender men; 4706 (47%) participants were university educated; 1537 (15%) participants had never been tested for HIV; and 389 (4%) participants were taking pre-exposure prophylaxis. At enrolment, 7282 (72%) participants reported condomless anal sex with at least one male partner in the previous 3 months. In the BT group, of the 4511 participants for whom HIV testing information was available, 4263 (95%) reported having used the free HIV self-test kit within 3 months.Within 3 months of enrolment there were 19 confirmed new HIV diagnoses (0·31%) in 6049 participants in the BT group and 15 (0·37%) of 4062 in the nBT group (p=0·64). INTERPRETATION: The offer of a single, free HIV self-test did not lead to increased rates of new HIV diagnoses, which could reflect decreasing HIV incidence rates in the UK. Nonetheless, the offer of a free HIV self-testing kit resulted in high HIV testing rates, indicating that self-testing is an attractive testing option for a large group of men who have sex with men. FUNDING: UK National Institute for Health and Care Research

Selected examples of the ability to differentiate between catfish allelic variants and gene duplicates (paralogues) using both blue catfish and channel catfish sequences

<p><b>Copyright information:</b></p><p>Taken from "Towards the ictalurid catfish transcriptome: generation and analysis of 31,215 catfish ESTs"</p><p>http://www.biomedcentral.com/1471-2164/8/177</p><p>BMC Genomics 2007;8():177-177.</p><p>Published online 18 Jun 2007</p><p>PMCID:PMC1906771.</p><p></p> Highly similar channel catfish sequences (Channel) and at least one blue catfish sequence (Blue) sharing the same BLAST identity were subjected to phylogenetic analysis. The topological stability of the neighbor joining trees was evaluated by 1000 bootstrapping replications, and the bootstrapping values are indicated by numbers at the nodes. Channel catfish and blue catfish genes placed into the same clade indicate that the additional, related channel catfish sequence is likely a paralogue rather than an allelic variant