Cochraneholgersen1149

The conservation of pathways and genes across species has allowed scientists to use non-human model organisms to gain a deeper understanding of human biology. However, the use of traditional model systems such as mice, rats, and zebrafish is costly, time-consuming and increasingly raises ethical concerns, which highlights the need to search for less complex model organisms. Existing tools only focus on the few well-studied model systems, most of which are complex animals. To address these issues, we have developed Orthologous Matrix and Alternative Model Organisms, a software and a web service that provide the user with the best non-complex organism for research into a biological process of interest based on orthologous relationships between human and the species. The outputs provided by OMAMO were supported by a systematic literature review.

https//omabrowser.org/omamo/, https//github.com/DessimozLab/omamo.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.

The goal of this study was to investigate the overall survival between open and thoracoscopic oesophagectomy in patients with oesophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (NCRT).

The Taiwan Cancer Registry was queried for ESCC from 2008 to 2016. We enrolled 2250 patients with ESCC receiving NCRT plus open (n = 487) or thoracoscopic (n = 1763) oesophagectomy. One-to-two propensity score matching between open and thoracoscopic oesophagectomy was performed. Overall survival was compared between the 2 groups before and after propensity score matching. Univariable analysis and multivariable analysis were performed to identify prognostic factors.

After one-to-two propensity score matching, 353 patients were in the open group and 706 patients were in the thoracoscopic group. The 3-year overall survival rates for matched patients treated with open or thoracoscopic oesophagectomy were similar (39.18% vs 44.33%, p = 0.11). Better overall survival was associated with thoracosm survival in patients with ESCC undergoing NCRT. Stage-specific comparisons showed that thoracoscopic oesophagectomy is associated with better survival than open oesophagectomy in patients with the pathological complete response, y-pathological III and y-pathological T0N+ stages and with similar survival in y-pathological I/II patients.

Hundreds of gene expression signatures have been developed during the last two decades. However, due to the multitude of development procedures and sometimes a lack of explanation for their implementation, it can become challenging to apply the original method on custom data. Moreover, at present there is no unified and tidy interface to compute signature scores with different single sample enrichment methods. For these reasons, we developed hacksig, an R package intended as a unified framework to obtain single sample scores with a tidy output as well as a collection of manually curated gene signatures and methods from cancer transcriptomics literature.

The hacksig R package is freely available on CRAN (https//CRAN.R-project.org/package=hacksig) under the MIT license. The source code can be found on GitHub at https//github.com/Acare/hacksig.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.Immune-checkpoint inhibitors have had impressive efficacy in some patients with cancer, reinvigorating long-term durable immune responses against tumors. Despite the clinical success of these therapies, most patients with cancer continue to be unresponsive to these treatments, highlighting the need for novel therapeutic options. Although P-selectin glycoprotein ligand-1 (PSGL-1) has been shown to inhibit immune responses in a variety of disease models, previous work has yet to address whether PSGL-1 can be targeted therapeutically to promote antitumor immunity. Using an aggressive melanoma tumor model, we targeted PSGL-1 in tumor-bearing mice and found increased effector CD4+ and CD8+ T-cell responses and decreased regulatory T cells (Treg) in tumors. T cells exhibited increased effector function, activation, and proliferation, which delayed tumor growth in mice after anti-PSGL-1 treatment. Targeting PD-1 in PSGL-1-deficient, tumor-bearing mice led to an increased frequency of mice with complete tumor eradication. Targeting both PSGL-1 and PD-1 in wild-type tumor-bearing mice also showed enhanced antitumor immunity and slowed melanoma tumor growth. Our findings showed that therapeutically targeting the PSGL-1 immune checkpoint can reinvigorate antitumor immunity and suggest that targeting PSGL-1 may represent a new therapeutic strategy for cancer treatment.

Both methotrexate and tioguanine can be considered as treatment options in patients with Crohn's disease after failure of conventional thiopurines. This study aimed to compare tolerability and drug survival of methotrexate and tioguanine therapy after failure of conventional thiopurines in patients with Crohn's disease.

We conducted a retrospective, multi-centre study, including patients with Crohn's disease initiating monotherapy methotrexate or tioguanine after failure (all causes) of conventional thiopurines. Follow-up duration was 104 weeks or until treatment discontinuation. The primary outcome was cumulative therapy discontinuation incidence due to adverse events. Secondary outcomes included total number of (serious) adverse events, and ongoing monotherapy.

In total, 219 patients starting either methotrexate (n=105) or tioguanine (n=114) were included. Sixty-five (29.7%) patients (methotrexate 43.8% [46/105 people]; tioguanine 16.7% [19/114 people], p<0.001) discontinued their treatment due to tioguanine (17%) in Crohn's disease patients after failure of conventional thiopurines. The total adverse events incidence during methotrexate use was higher, while serious adverse events incidence was similar. These favourable results for tioguanine treatment may guide the selection of immunosuppressive therapy after failure of conventional thiopurines.

Interactions between ecological factors and seed physiological responses during the establishment phase shape the distribution of plants. Yet, our understanding of the functions and evolution of early-life traits has been limited by the scarcity of large-scale datasets. Here, we tested the hypothesis that the germination niche of temperate plants is shaped by their climatic requirements and phylogenetic relatedness, using germination data sourced from a comprehensive seed conservation database of the European flora (ENSCOBASE).

We performed a phylogenetically informed Bayesian meta-analysis of primary data, considering 18 762 germination tests of 2418 species from laboratory experiments conducted across all European geographical regions. We tested for the interaction between species' climatic requirements and germination responses to experimental conditions including temperature, alternating temperature, light and dormancy-breaking treatments, while accounting for between-study variation related to seed s addition, our methodological approach highlighted how large datasets generated by conservation seed banking can be valuable sources to address questions in plant macroecology and evolution.

This is the first quantitative meta-analysis of the germination niche at a continental scale. Our findings showed that the germination niches of European plants exhibit evolutionary convergence mediated by strong pressures at the macroclimatic level. In addition, our methodological approach highlighted how large datasets generated by conservation seed banking can be valuable sources to address questions in plant macroecology and evolution.

We pooled ambulatory blood pressure monitoring data from 5 US studies, including the Jackson Heart Study (JHS), the Coronary Artery Risk Development in Young Adults (CARDIA) study, the Masked Hypertension Study, the Improving the Detection of Hypertension Study, and the North Carolina Masked Hypertension Study. Using a cross-sectional study design, we estimated differences in the prevalence of masked hypertension by race/ethnicity when out-of-office blood pressure (BP) included awake, asleep, and 24-hour BP vs. awake BP alone.

We restricted the analyses to participants with office systolic BP (SBP) <130 mm Hg and diastolic BP (DBP) <80 mm Hg. High awake BP was defined as mean SBP/DBP ≥130/80 mm Hg, high asleep BP as mean SBP/DBP ≥110/65 mm Hg, and high 24-hour BP as mean SBP/DBP ≥125/75 mm Hg.

Among participants not taking antihypertensive medication (n = 1,292), the prevalence of masked hypertension with out-of-office BP defined by awake BP alone or by awake, asleep, or 24-hour BP was 34.5% and 48.7%, respectively, among non-Hispanic White, 39.7% and 67.6% among non-Hispanic Black, and 19.4% and 35.1% among Hispanic participants. After multivariable adjustment, non-Hispanic Black were more likely than non-Hispanic White participants to have masked hypertension by asleep or 24-hour BP but not awake BP (adjusted odds ratio [OR] 2.14 95% confidence interval [CI] 1.45-3.15) and by asleep or 24-hour BP and awake BP (OR 1.61; 95% CI 1.12-2.32) vs. not having masked hypertension.

Assessing asleep and 24-hour BP measures increases the prevalence of masked hypertension more among non-Hispanic Black vs. non-Hispanic White individuals.

Assessing asleep and 24-hour BP measures increases the prevalence of masked hypertension more among non-Hispanic Black vs. non-Hispanic White individuals.Ribosomes are a complex ensemble of rRNA and ribosomal proteins that function as mRNA translation machines. Ribosome biogenesis is a multistep process that begins in the nucleolus and concludes in the cytoplasm. The process is tightly controlled by multiple checkpoint and surveillance pathways. Perturbations in these checkpoints and pathways can lead to hyperactivation of ribosome biogenesis. Emerging evidence suggests that cancer cells harbor a specialized class of ribosomes (onco-ribosomes) that facilitates the oncogenic translation program, modulates cellular functions, and promotes metabolic rewiring. Mutations in ribosomal proteins, rRNA processing, and ribosome assembly factors result in ribosomopathies that are associated with an increased risk of developing malignancies. Recent studies have linked mutations in ribosomal proteins and aberrant ribosomes with poor prognosis, highlighting ribosome-targeted therapy as a promising approach for treating patients with cancer. Here, we summarize various aspects of dysregulation of ribosome biogenesis and the impact of resultant onco-ribosomes on malignant tumor behavior, therapeutic resistance, and clinical outcome. Ribosome biogenesis is a promising therapeutic target, and understanding the important determinants of this process will allow for improved and perhaps selective therapeutic strategies to target ribosome biosynthesis.MicroRNA childhood Cancer Catalog (M3Cs) is a high-quality curated collection of published miRNA research studies on 16 pediatric cancer diseases. M3Cs scope was based on two approaches data-driven clinical significance and data-driven human pediatric cell line models. Based on the translational bioinformatics spectrum, the main objective of this study is to bring miRNA research into clinical significance in both pediatric cancer patient care and drug discovery toward health informatics in childhood cancer. M3Cs development passed through three phases 1. Leukadherin-1 Literature Mining It includes external database search and screening. 2. Data processing that includes three steps (a) Data Extraction, (b) Data Curation and annotation, (c) Web Development. 3. Publishing Shinyapps.io was used as a web interface for the deployment of M3Cs. M3Cs is now available online and can be accessed through https//m3cs.shinyapps.io/M3Cs/. For data-driven clinical significance approach, 538 miRNAs from 268 publications were reported in the clinical domain while 7 miRNAs from 5 publications were reported in the clinical & drug domain.