Harboeovergaard1310

To develop and validate a gout flare risk stratification tool for people with gout hospitalised for non-gout conditions.

The prediction rule for inpatient gout flare was derived from a cohort of 625 hospitalised people with comorbid gout from New Zealand. The rule had four items (1) no pre-admission GOut flare prophylaxis, (2) no pre-admission Urate-lowering therapy, (3) Tophus and (4) pre-admission serum urate >0.36 mmol/l within the previous year (GOUT-36 rule). Two or more items are required for the classification of high risk for developing inpatient gout flare. The GOUT-36 rule was validated in a prospective cohort of 284 hospitalised people with comorbid gout from Thailand and China.

The GOUT-36 rule had a sensitivity of 75%, specificity of 67% and AUC of 0.71 for classifying people at high risk for developing inpatient gout flare. Four risk groups were developed low (no items), moderate (one item), high (two items) and very high risk (three or four items). In a population with frequent (overall 34%) in-hospital gout flare, 80% of people with very high risk people developed flare, while 11% of low-risk people had inpatient flare.

GOUT-36 rule is simple and sensitive for classifying people with high risk for inpatient gout flare. The rule may help inform clinical decision and future research on the prevention of inpatient gout flare.

GOUT-36 rule is simple and sensitive for classifying people with high risk for inpatient gout flare. The rule may help inform clinical decision and future research on the prevention of inpatient gout flare.Intestinal organoids better represent in vivo intestinal properties than conventionally used established cell lines in vitro. However, they are maintained in three-dimensional culture conditions that may be accompanied by handling complexities. We characterized the properties of human organoid-derived two-dimensionally cultured intestinal epithelial cells (IECs) compared with those of their parental organoids. We found that the expression of several intestinal markers and functional genes were indistinguishable between monolayer IECs and organoids. We further confirmed that their specific ligands equally activate intestinal ligand-activated transcriptional regulators in a dose-dependent manner. The results suggest that culture conditions do not significantly influence the fundamental properties of monolayer IECs originating from organoids, at least from the perspective of gene expression regulation. This will enable their use as novel biological tools to investigate the physiological functions of the human intestine.

Genome sequencing projects annotate protein-coding gene models with multiple transcripts, aiming to represent all of the available transcript evidence. However, downstream analyses often operate on only one representative transcript per gene locus, sometimes known as the canonical transcript. To choose canonical transcripts, TRaCE (Transcript Ranking and Canonical Election) holds an 'election' in which a set of RNA-seq samples rank transcripts by annotation edit distance. These sample-specific votes are tallied along with other criteria such as protein length and InterPro domain coverage. The winner is selected as the canonical transcript, but the election proceeds through multiple rounds of voting to order all the transcripts by relevance. Based on the set of expression data provided, TRaCE can identify the most common isoforms from a broad expression atlas or prioritize alternative transcripts expressed in specific contexts.

Transcript ranking code can be found on GitHub at https//github.com/warelab/TRaCE.

Additional data are available in the GitHub repository.

Additional data are available in the GitHub repository.Lipids exert many essential physiological functions, such as serving as a structural component of biological membranes, storing energy, and regulating cell signal transduction. Dysregulation of lipid metabolism can lead to dyslipidemia related to various human diseases, such as obesity, diabetes, and cardiovascular disease. Therefore, lipid metabolism is strictly regulated through multiple mechanisms at different levels, including the extracellular matrix. check details Membrane-type I matrix metalloproteinase (MT1-MMP), a zinc-dependent endopeptidase, proteolytically cleaves extracellular matrix components and non-matrix proteins, thereby regulating many physiological and pathophysiological processes. Emerging evidence supports the vital role of MT1-MMP in lipid metabolism. For example, MT1-MMP mediates ectodomain shedding of low-density lipoprotein receptor and increases plasma low-density lipoprotein cholesterol levels and the development of atherosclerosis. It also increases the vulnerability of atherosclerotic plaque by promoting collagen cleavage. Furthermore, it can cleave the extracellular matrix of adipocytes, affecting adipogenesis and the development of obesity. Therefore, the activity of MT1-MMP is strictly regulated by multiple mechanisms, such as autocatalytic cleavage, endocytosis and exocytosis, and posttranslational modifications. Here, we summarize the latest advances in MT1-MMP, mainly focusing on its role in lipid metabolism, the molecular mechanisms regulating the function and expression of MT1-MMP, and their pharmacotherapeutic implications.

TikTok is one of the most popular and fastest growing social media apps in the world. Previous studies have analyzed the quality of patient education information on older video platforms, but the quality of plastic and cosmetic surgery videos on TikTok has not yet been determined.

To analyze the source and quality of certain cosmetic procedure videos on TikTok.

The TikTok mobile application was queried for content related to two popular face procedures (rhinoplasty and blepharoplasty) and two body procedures (breast augmentation and abdominoplasty). Two independent reviewers analyzed video content according to the DISCERN scale, a validated, objective criteria that assesses the quality of information on a scale of 1-5. Quality scores were compared between videos produced by medical and nonmedical creators and between different content categories.

There were 4.8 billion views and 76.2 million likes across included videos. Videos were created by MDs (56%) and laypersons (44%). Overall average DISCERN score out of 5 corresponded to very poor video quality for rhinoplasty (1.55), blepharoplasty (1.44), breast augmentation (1.25) and abdominoplasty (1.29). DISCERN scores were significantly higher among videos produced by MDs than by laypersons for all surgeries. Comedy videos consistently had the lowest average DISCERN scores, while educational videos had the highest.

It is increasingly important that medical professionals understand the possibility of patient misinformation in the age of social media. We encourage medical providers to be involved in creating quality information on TikTok and educate patients about misinformation to best support health literacy.

It is increasingly important that medical professionals understand the possibility of patient misinformation in the age of social media. We encourage medical providers to be involved in creating quality information on TikTok and educate patients about misinformation to best support health literacy.

Nitrogen fixation in legumes requires tight control of carbon and nitrogen balance. Thus, legumes control nodule numbers via an autoregulation mechanism. 'Autoregulation of nodulation' mutants super-nodulate and are thought to be carbon-limited due to the high carbon-sink strength of excessive nodules. This study aimed to examine the effect of increasing carbon supply on the performance of super-nodulation mutants.

We compared the responses of Medicago truncatula super-nodulation mutants (sunn-4 and rdn1-1) and wild type to five CO2 levels (300-850 μmol mol -1). Nodule formation and N2 fixation were assessed in soil-grown plants at 18 and 42 days after sowing.

Shoot and root biomass, nodule number and biomass, nitrogenase activity and fixed-N per plant of all genotypes increased with increasing CO2 concentration and reached the maximum around 700 μmol mol -1. While the sunn-4 mutant showed strong growth-retardation compared to wild-type plants, elevated CO2 increased shoot biomass and total N content of rdn1-1 mutant up to two-fold. This was accompanied by a four-fold increase in nitrogen fixation capacity in the rdn1-1 mutant.

These results suggest that the super-nodulation phenotype per se did not limit growth. The additional nitrogen fixation capacity of the rdn1-1 mutant may enhance the benefit of elevated CO2 on plant growth and N2 fixation.

These results suggest that the super-nodulation phenotype per se did not limit growth. The additional nitrogen fixation capacity of the rdn1-1 mutant may enhance the benefit of elevated CO2 on plant growth and N2 fixation.Gene-smoking interactions play important roles in the development of non-small cell lung cancer (NSCLC). To identify single nucleotide polymorphisms (SNPs) that modify the association of smoking behavior with NSCLC risk, we conducted a genome-wide gene-smoking interaction study in Chinese populations. The genome-wide interaction analysis between SNPs and smoking status (ever- versus never-smokers) was carried out using genome-wide association studies (GWAS) of NSCLC, which included 13,327 cases and 13,328 controls. Stratified analysis by histological subtypes was also conducted. We used a genome-wide significance threshold of 5×10 -8 for identifying significant gene-smoking interactions and 1×10 -6 for identifying suggestive results. Functional annotation was performed to identify potential functional SNPs and target genes. We identified three novel loci with significant or suggestive gene-smoking interaction. For NSCLC, the interaction between rs2746087 (20q11.23) and smoking status reached genome-wide significance threshold (OR = 0.63, 95%CI 0.54-0.74, P = 3.31×10 -8), and the interaction between rs11912498 (22q12.1) and smoking status reached suggestive significance threshold (OR = 0.72, 95%CI 0.63-0.82, P = 8.10×10 -7). Stratified analysis by histological subtypes identified suggestive interactions between rs459724 (5q11.2) and smoking status (OR = 0.61, 95%CI 0.51-0.73, P = 7.55×10 -8) in the risk of lung squamous cell carcinoma. Functional annotation indicated that both classic and novel biological processes, including nicotine addiction and airway clearance, may modulate the susceptibility to NSCLC. These novel loci provide new insights into the biological mechanisms underlying NSCLC risk. Independent replication in large-scale studies is needed and experimental studies are warranted to functionally validate these associations.Allogeneic hematopoietic stem cell transplantation (HSCT) may potentially cure patients with chronic lymphocytic leukemia (CLL) and Richter's transformation (CLL-RT) or CLL without RT, but the impact of novel agents on HSCT is unclear. CLL-RT patients have a grave prognosis, and their outcomes after HSCT are uncertain. We conducted a retrospective analysis of all 58 CLL patients, including 23 CLL-RT patients, who underwent reduced intensity conditioning (RIC) HSCT at Memorial Sloan Kettering Cancer Center (New York, NY) between September 2006 and April 2017. With a median follow-up of 68 months (range, 24-147 months), 5-year progression-free survival (PFS) was 40% (95% confidence interval [CI], 28%-56%), and overall survival (OS) was 58% (95% CI, 48%-74%). The 1-year graft-versus-host disease/relapse-free survival (GRFS) was 38% (95% CI, 25%-50%). Patients with CLL-RT and CLL patients without RT had comparable outcomes. In both cohorts, treatment-sensitive response and ≤3 previous lines of therapy produced superior PFS and OS.