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Metabarcoding of microbial eukaryotes (collectively known as protists) has developed tremendously in the last decade, almost solely relying on the 18S rRNA gene. As microbial eukaryotes are extremely diverse, many primers and primer pairs have been developed. trans-C75 To cover a relevant and representative fraction of the protist community in a given study system, an informed primer choice is necessary, as no primer pair can target all protists equally well. As such, a smart primer choice is very difficult even for experts and there are very few online resources available to list existing primers. We built a database listing 285 primers and 83 unique primer pairs that have been used for eukaryotic 18S rRNA gene metabarcoding. In silico performance of primer pairs was tested against two sequence databases PR2 version 4.12.0 for eukaryotes and a subset of silva version 132 for bacteria and archaea. We developed an R-based web application enabling browsing of the database, visualization of the taxonomic distribution of the amplified sequences with the number of mismatches, and testing any user-defined primer or primer set (https//app.pr2-primers.org). Taxonomic specificity of primer pairs, amplicon size and location of mismatches can also be determined. We identified universal primer sets that matched the largest number of sequences and analysed the specificity of some primer sets designed to target certain groups. This tool enables guided primer choices that will help a wide range of researchers to include protists as part of their investigations.

While interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc), there remains a paucity of predictive markers to assess disease progression. We previously demonstrated that adipose tissue metabolism and adipokine homeostasis is dysregulated in SSc. We sought to determine the association and predictive ability of the novel adipokine C1q/TNF-Related Protein 9 (CTRP9) for SSc-ILD.

We performed a retrospective longitudinal study utilizing the Northwestern Scleroderma Program Patient Registry and Biorepository. Serum levels of CTRP9 were measured in 110 SSc patients at baseline, and demographic, clinical and pulmonary function test data were collected in 12-month intervals to 48 months. Longitudinal trajectory of forced vital capacity percent predicted (FVC%) was used as a primary outcome measure. We utilized a mixed model to compare trajectories of lung function by CTRP9 groups and performed latent trajectory analysis to accommodate for heterogeneity.

In cross-sectional analysis, elevated circulating CTRP9 was associated with significantly lower FVC% at baseline (72%±17 vs. 80%±18, p=0.02) and 48 months (68±19 vs. 84±18, p=0.001). In mixed model analysis, high CTRP9 was associated with worse lung function, but not with a different trajectory (p=0.23). In contrast, low CTRP9 identified patients with stability of lung disease with reasonable accuracy (sensitivity=73%). Latent trajectory analysis confirmed the association of lower CTRP9 with higher FVC%.

Higher circulating CTRP9 associated with worse pulmonary function while low CTRP9 identified patients with lung disease stability over time. These findings suggest that CTRP9 may be a potential biomarker in SSc-associated ILD.

Higher circulating CTRP9 associated with worse pulmonary function while low CTRP9 identified patients with lung disease stability over time. These findings suggest that CTRP9 may be a potential biomarker in SSc-associated ILD.Alkylammonium cation affinities of 64 nitrogen-containing organobases, as well as the respective proton transfer processes from the alkylammonium cations to the base, have been computed in the gas phase by using DFT methods. The guanidine bases show the highest proton transfer values (191.9-233 kJ mol-1 ) whereas the cis-2,2′-biimidazole presents the largest affinity towards the alkylammonium cations (>200 kJ mol-1 ) values. The resulting data have been compared with the experimentally reported proton affinities of the studied nitrogen-containing organobases revealing that the propensity of an organobase for the proton transfer process increases linearly with its proton affinity. This work can provide a tool for designing senors for bioactive compounds containing amino groups that are protonated at physiological pH.Hormone receptor testing mainly serves the purpose of guiding treatment choices for breast cancer patients. Patients with estrogen receptor (ER)-positive breast cancers show significant response to endocrine therapy. However, the methods to define ER status and eligibility for treatment remain controversial. Despite recent guidelines considering staining ≥1% of tumor nuclei by immunohistology as ER-positive, it has raised concerns on the benefit of endocrine therapy for tumors with ER 1%-10% expression, termed “ER-low positive”. This subgroup accounts for 3% to 9% of all patients and is likely to have unique molecular features, and therefore distinct therapeutic response to endocrine therapy compared with ER-high positive tumors. The latest guidelines did not provide detailed descriptions for those patients, resulting in inconsistent treatment strategies. Consequently, we aimed to resolve this dilemma comprehensively. This review discusses molecular traits and recent ER-low positive breast cancer innovations, highlighting molecular-targeted treatment rather than traditional unified endocrine therapy for future basic and clinical research.

To examine efficacy and safety of tramadol for knee or hip osteoarthritis (OA).

Pubmed, Embase, Cochrane Library and Web of Science were searched up to May 2020 for randomized controlled trials (RCTs) comparing any of the following interventions tramadol 100 mg/day, 200 mg/day and 300 mg/day, and placebo for knee or hip OA. Pain and function were measured at or nearest to twelve weeks for efficacy. Gastrointestinal, cardiovascular and central nervous system (CNS) adverse effects (AEs), and withdrawals were measured for safety. Bayesian network meta-analysis was conducted.

Six RCTs (3,611 participants) were included. Tramadol 100 mg/day (standardized mean difference [SMD]=-0.16, 95% confidence interval [CI] -0.34 to 0.00), 200 mg/day (SMD=-0.21, 95%CI -0.37 to -0.06) and 300 mg/day (SMD=-0.30, 95%CI -0.48 to -0.14) were statistically more effective than placebo in pain relief, but only tramadol 300 mg/day was better than placebo in functional improvement (SMD=-0.24, 95%CI -0.47 to -0.03). Tramadol 100 mg/day (relative risk [RR]=2.