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The efficiency of CRISPR/Cas9-mediated protein knockout is determined by three factors sequence-specific sgRNA activity, frameshift probability, and the characteristics of targeted amino acids. A number of computational methods have been developed for predicting sgRNA efficiency from different perspectives. However, an integrative method that combines all three factors for rational sgRNA selection is still lacking.<br /><br /> We developed GuidePro, a two-layer ensemble predictor that enables the integration of multiple factors for the prioritization of sgRNAs in protein knockouts. Tested on independent datasets, GuidePro outperforms existing methods and demonstrates consistent superior performance in predicting phenotypes caused by protein loss-of-function, suggesting its robustness for prioritizing sgRNAs in various applications of CRISPR/Cas9 knockouts.<br /><br /> GuidePro is available at https//github.com/MDhewei/GuidePro. [https://www.selleckchem.com/products/ms4078.html MS4078] A web application for prioritizing sgRNAs that target protein-coding genes in human, monkey and mouse genomes is available at https//bioinformatics.mdanderson.org/apps/GuidePro.<br /><br /> Supplementary data are available at Bioinformatics online.<br /><br />Supplementary data are available at Bioinformatics online.<br /><br /> Weight reduction may reduce serum uric acid (SUA). This study aimed to examine the changes of SUA before and after bariatric surgery in patients with obesity with or without hyperuricaemia and gout.<br /><br /> This is a retrospective analysis of 147 routinely collected data on hospital patients with obesity who underwent bariatric surgery. The body weight and SUA were measured at baseline and after surgery at 1-7 days, 1, 3, 6 and 12 months.<br /><br /> The mean (95% CI) weight reduction of 147 patients was 30.7 (28.7, 32.7) kg 1 year after surgery (P &lt; 0.001). SUA decreased rapidly from 419.0 (400.1, 437.8) µmol/l at baseline to 308.4 (289.6, 327.2) µmol/l at 1-7 days, flared up to 444.8 (423.9, 465.6) µmol/l at 1 month, then decreased again to 383.8 (361.5, 406.1) µmol/l at 3 months, 348.9 (326.3, 371.5) µmol/l at 6 months and 327.9 (305.3, 350.5) µmol/l at 12 months (P &lt; 0.001). Similar trends but more rapid reductions were observed in 55 hyperuricaemia patients and 25 gout patients. All 25 gout patients had an elevated SUA above the therapeutic target (≥360µmmol/l) at baseline, but in 10 patients it was reduced below this target at 12 months. The mean reduction (95% CI) of SUA in all patients and gout patients was 84.3 (63.1-105.4) and 163.6 (103.9, 223.3) µmmol/l, respectively.<br /><br /> Bariatric surgery significantly reduces body weight and SUA for obese patients with hyperuricaemia and gout. Gout may be considered as an indicator for this surgical treatment in people with severe obesity.<br /><br />Bariatric surgery significantly reduces body weight and SUA for obese patients with hyperuricaemia and gout. Gout may be considered as an indicator for this surgical treatment in people with severe obesity.<br /><br /> Starting in 2019 policies restricting the availability of flavored e-cigarette products were proposed or implemented in the U.S. to curb vaping by youth. People took to Twitter to voice their opposition, referencing the phrase "Flavors Save Lives". This study documented the emerging themes pertaining to "Flavors Saves Lives" over a 12-month period.<br /><br /> The study period was from May 1, 2019 to May 1, 2020. A stratified sampling procedure supplied 2500 tweets for analysis. Posts were classified by one or more of the following themes 1) Political Referendum; 2) Institutional Distrust; 3) Individual Rights; 4) Misinformation; 5) THC Vaping is the Real Problem; 6) Smoking Cessation; 7) Adult Use; and 8) Not a Bot. The temporal pattern of tweets over the year was examined.<br /><br /> Political Referendum (76.5%) and Institutional Distrust (31.3%) were the most prominent themes, followed by Not a Bot (11.0%), Individual Rights (10.4%), Adult Use (8.0%), Smoking Cessation (6.6%), Misinformation (5.9%), and THC Vaping is the Real Problem (3.5%). Total tweet frequencies increased in September 2019 and peaked in November 2019 before returning to relatively low numbers. Political Referendum and Institutional Distrust were consistently the most prevalent themes over time.<br /><br /> Twitter posts with the phrase "Flavors Save Lives" commonly discussed voting against political incumbents and mentioned distrust of government representatives. Findings demonstrated the possibility of near real time Twitter monitoring of public opposition to flavor bans. These data may be valuable for designing tobacco control information campaigns in the future.<br /><br />Twitter posts with the phrase "Flavors Save Lives" commonly discussed voting against political incumbents and mentioned distrust of government representatives. Findings demonstrated the possibility of near real time Twitter monitoring of public opposition to flavor bans. These data may be valuable for designing tobacco control information campaigns in the future.A growing number of people desire ART with cryopreserved donor oocytes. The allocation of these oocytes to couples and mothers to be is a 2-fold process. The first step is to select a pool of recipients. The second step is to decide who should be treated first. Prioritizing recipients is critical in settings where demand outstrips supply. So far, the issue of how to fairly allocate cryopreserved donor oocytes has been poorly addressed. Our ethical analysis aims to support clinics involved in allocation decisions by formulating criteria for recipient selection irrespective of supply (Part I) and recipient prioritization in case supply is limited (Part II). Relevant criteria for recipient selection are a need for treatment to experience parenthood; a reasonable chance for successful treatment; the ability to safely undergo an oocyte donation pregnancy; and the ability to establish a stable and loving relationship with the child. Recipients eligible for priority include those who have limited time left for treatment; have not yet experienced parenthood; did not undergo previous treatment with cryopreserved donor oocytes; and contributed to the supply of donor oocytes by bringing a donor to the bank. While selection criteria function as a threshold principle, we argue that the different prioritization criteria should be carefully balanced. Since specifying and balancing the allocation criteria undoubtedly raises a moral dispute, a fair and legitimate allocation process is warranted (Part III). We argue that allocation decisions should be made by a multidisciplinary committee, staffed by relevant experts with a variety of perspectives. Furthermore, the committees' reasoning behind decisions should be transparent and accessible to those affected clinicians, donors, recipients and children born from treatment. Insight into the reasons that underpin allocation decisions allows these stakeholders to understand, review and challenge decisions, which is also known as accountability for reasonableness.<br /><br /> To investigate the prevalence and genetic contexts of the blaCTX-M-14 gene harboured by foodborne isolates of Vibrio spp. in China.<br /><br /> A total of 1856 Vibrio spp. isolates collected from raw meat and shrimp samples in Guangdong Province of China were screened for blaCTX-M-14 by PCR. The blaCTX-M-14-positive isolates were characterized by MIC, PFGE, MLST, conjugation, S1-PFGE and Southern blotting and WGS using Illumina and Nanopore platforms.<br /><br /> A total of 35 (1.9%) Vibrio isolates were positive for blaCTX-M-14, including 33 Vibrio parahaemolyticus strains and two Vibrio alginolyticus strains. MLST showed that most of the blaCTX-M-14-bearing isolates could be assigned into two major STs, with ST163 being more prevalent (n = 23), followed by ST180 (n = 6). Whole-genome analysis of these 35 isolates revealed that the blaCTX-M-14 gene was associated with ISEcp1 in the upstream region, of which 32 blaCTX-M-14 genes were located in the same loci of chromosome I, 1 blaCTX-M-14 gene was located in a novel chromosomal integrative conjugative element (ICE) belonging to the SXT/R391 family and 2 blaCTX-M-14 genes were located in the same type of plasmid, which belonged to the IncP-1 group. Conjugation experiments showed that only the plasmid-borne blaCTX-M-14 gene could be transferred to the recipient strain Escherichia coli J53.<br /><br /> The emergence of the novel ICE and IncP-1 plasmids has contributed to the variable genetic contexts of blaCTX-M-14 among strains of Vibrio spp. and facilitated the horizontal transfer of such genes between Vibrio spp. and other zoonotic pathogens, resulting in a rapid increase in the prevalence of blaCTX-M-14-bearing bacterial pathogens worldwide.<br /><br />The emergence of the novel ICE and IncP-1 plasmids has contributed to the variable genetic contexts of blaCTX-M-14 among strains of Vibrio spp. and facilitated the horizontal transfer of such genes between Vibrio spp. and other zoonotic pathogens, resulting in a rapid increase in the prevalence of blaCTX-M-14-bearing bacterial pathogens worldwide.<br /><br /> Ergot alkaloids are mycotoxins produced by the fungus Claviceps, which can contaminate grains and pose a health risk to humans and animals. Validation of an ergot alkaloid method in collaborative projects can be challenging due to instability of analytes, and lack of reliable reference materials and a fully validated reference methods.<br /><br /> To extensively evaluate performance of a quantitative UHPLC-MS/MS method to detect ten ergot alkaloids at concentrations between 16-500 ng/g in grains.<br /><br /> The method performance was evaluated in the Blinded Method Test (BMT) exercise, which allowed organizers to successfully address the challenges. Forty completely blinded test samples were prepared in an independent laboratory and shipped to participating laboratory to analyze on two separate days.<br /><br /> Precision, accuracy and HorRatr values met or exceeded the Food and Drug Administration (FDA) recommendations. The design of the BMT exercise provided a high degree of confidence in data and conclusions drawn.<br /><br /> The method performed in a manner as expected and the method can be used by the laboratory for routine testing of wheat and rye grains.<br /><br /> Blinded method tests of laboratory methods facilitate validation of tests by evaluating performance in an unbiased manner.<br /><br />Blinded method tests of laboratory methods facilitate validation of tests by evaluating performance in an unbiased manner.<br /><br /> Supplemental oxygen is commonly administered to pregnant women at the time of delivery to prevent fetal hypoxia and acidemia. There is mixed evidence on the utility of this practice.<br /><br /> To compare the association of peripartum maternal oxygen administration with room air on umbilical artery (UA) gas measures and neonatal outcomes.<br /><br /> Ovid MEDLINE, Embase, Scopus, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials were searched from February 18 to April 3, 2020. Search terms included labor or obstetric delivery and oxygen therapy and fetal blood or blood gas or acid-base imbalance.<br /><br /> Studies were included if they were randomized clinical trials comparing oxygen with room air at the time of scheduled cesarean delivery or labor in patients with singleton, nonanomalous pregnancies. Studies that did not collect paired umbilical cord gas samples or did not report either UA pH or UA Pao2 results were excluded.<br /><br /> Data were extracted by 2 independent reviewers. The analysis was stratified by the presence or absence of labor at the time of randomization.