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.
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.
GuidePro is available at https//github.com/MDhewei/GuidePro. 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.
Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.
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.
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.
The mean (95% CI) weight reduction of 147 patients was 30.7 (28.7, 32.7) kg 1 year after surgery (P < 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 < 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.
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.
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.
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.
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.
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.
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.
Twitter posts with the phrase "Flavors Save Lives" commonly discussed voting against political incumbents and mentioned distrust of government representatives. https://www.selleckchem.com/products/tapi-1.html 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.
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.
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.
GuidePro is available at https//github.com/MDhewei/GuidePro. 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.
Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.
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.
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.
The mean (95% CI) weight reduction of 147 patients was 30.7 (28.7, 32.7) kg 1 year after surgery (P < 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 < 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.
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.
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.
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.
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.
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.
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.
Twitter posts with the phrase "Flavors Save Lives" commonly discussed voting against political incumbents and mentioned distrust of government representatives. https://www.selleckchem.com/products/tapi-1.html 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.
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