Takshan/R1 huggingface dataset:
MiR-20a-5p suppresses tumor proliferation by targeting autophagy-related gene 7 in neuroblastoma.

Background: Neuroblastoma (NB) is the most common malignant tumor originating from the extracranial sympathetic nervous system in children. The molecular mechanisms underlying this disease are complex, and not completely understood. Methods: Quantitative real-time PCR (qRT-PCR) was applied to quantify the expression of miR-20a-5p and its target gene ATG7 in clinical NB tissues. The biological function of miR-20a-5p and ATG7 in SH-SY5Y cells was investigated through in vitro studies (Real-Time cell kinetic analyzer, colony formation assay, caspase-Glo 3/7 assay and western blotting). The luciferase reporter assay was conducted to verify the biological relationship between miR-20a-5p and ATG7. Results: Here we found that miR-20a-5p expression was significantly downregulated whereas its target autophagy-related gene 7 (ATG7) was increased along with clinical staging of NB progression. Correlation analysis showed that miR-20a-5p had a negative correlation trend with ATG7. In SH-SY5Y cells, forced expression of miR-20a-5p suppressed ATG7 expression, autophagy initiation and cellular proliferation while promoted apoptosis, suggesting a potential association between miR-20a-5p and ATG7. Further bioinformatic target prediction combined with protein expression and luciferase reporter assay verified that miR-20a-5p inhibited ATG7 by directly binding to its 3'-UTR, confirming the involvement of miR-20a-5p in the regulation of ATG7 in NB. Conclusions: These results clarified that miR-20a-5p inhibited cell proliferation and promoted apoptosis through negative regulation of ATG7 and thus autophagy suppression in SH-SY5Y cells. Therefore, defining the context-specific roles of autophagy in NB and regulatory mechanisms involved will be critical for developing autophagy-targeted therapeutics against NB. Both miR-20a-5p and ATG7 would be potential therapeutic targets for future NB treatment.
Development and feasibility of a web application to monitor patients' cancer-related pain.

BACKGROUND: In the outpatient setting, pain management is often inadequate in patients with cancer-related pain, because of patient- and professional-related barriers in communication and infrequent contacts. The internet may provide new opportunities for monitoring these patients. PURPOSE: The purpose of this study was to investigate whether internet monitoring of cancer-related pain in outpatients was feasible. METHODS: We developed an internet application that contained a pain diary, eConsult, and patient pain education. In the pain diary, patients scored their pain intensity (0-10 Numeric Rating Scale) and analgesic use daily and their side effects twice a week. Feasibility was defined as the percentage of diaries patients completed during the first 6 weeks. RESULTS: We included 100 outpatients. Sixteen were not evaluable due to cognitive problems (2); withdrawal of participation (2); internet problems (2), or because they were too ill (10). During the first 6 weeks, 60% of 84 evaluable patients completed their diary for at least 65% of the days (median number of diaries, 21; range, 3-42) and asked for a median of five eConsults (range, 0-37). Patients most frequently used an eConsult for questions about pain or side effects, how to use their analgesics and to improve their self-management. Over the 6-week period, current pain intensity decreased from 3.3 (SD = 2) to 2.5 (SD = 1.6, p = 0.005), and worst pain intensity decreased from 5.7 (SD = 2) to 3.8 (SD = 2.0, p < 0.001). CONCLUSION: Internet monitoring of pain is feasible in most outpatients with cancer-related pain. The frequent use of the pain diary in the majority of patients indicates that those patients felt confident with the regular assessment of pain.
Sipros Ensemble improves database searching and filtering for complex metaproteomics.

Motivation: Complex microbial communities can be characterized by metagenomics and metaproteomics. However, metagenome assemblies often generate enormous, and yet incomplete, protein databases, which undermines the identification of peptides and proteins in metaproteomics. This challenge calls for increased discrimination of true identifications from false identifications by database searching and filtering algorithms in metaproteomics. Results: Sipros Ensemble was developed here for metaproteomics using an ensemble approach. Three diverse scoring functions from MyriMatch, Comet and the original Sipros were incorporated within a single database searching engine. Supervised classification with logistic regression was used to filter database searching results. Benchmarking with soil and marine microbial communities demonstrated a higher number of peptide and protein identifications by Sipros Ensemble than MyriMatch/Percolator, Comet/Percolator, MS-GF+/Percolator, Comet & MyriMatch/iProphet and Comet & MyriMatch & MS-GF+/iProphet. Sipros Ensemble was computationally efficient and scalable on supercomputers. Availability and implementation: Freely available under the GNU GPL license at http://sipros.omicsbio.org. Contact: cpan@utk.edu. Supplementary information: Supplementary data are available at Bioinformatics online.
The impact of sequence database choice on metaproteomic results in gut microbiota studies.

BACKGROUND: Elucidating the role of gut microbiota in physiological and pathological processes has recently emerged as a key research aim in life sciences. In this respect, metaproteomics, the study of the whole protein complement of a microbial community, can provide a unique contribution by revealing which functions are actually being expressed by specific microbial taxa. However, its wide application to gut microbiota research has been hindered by challenges in data analysis, especially related to the choice of the proper sequence databases for protein identification. RESULTS: Here, we present a systematic investigation of variables concerning database construction and annotation and evaluate their impact on human and mouse gut metaproteomic results. We found that both publicly available and experimental metagenomic databases lead to the identification of unique peptide assortments, suggesting parallel database searches as a mean to gain more complete information. In particular, the contribution of experimental metagenomic databases was revealed to be mandatory when dealing with mouse samples. Moreover, the use of a "merged" database, containing all metagenomic sequences from the population under study, was found to be generally preferable over the use of sample-matched databases. We also observed that taxonomic and functional results are strongly database-dependent, in particular when analyzing the mouse gut microbiota. As a striking example, the Firmicutes/Bacteroidetes ratio varied up to tenfold depending on the database used. Finally, assembling reads into longer contigs provided significant advantages in terms of functional annotation yields. CONCLUSIONS: This study contributes to identify host- and database-specific biases which need to be taken into account in a metaproteomic experiment, providing meaningful insights on how to design gut microbiota studies and to perform metaproteomic data analysis. In particular, the use of multiple databases and annotation tools has to be encouraged, even though this requires appropriate bioinformatic resources.
Metaproteomic data analysis at a glance: advances in computational microbial community proteomics.

INTRODUCTION: Within the last decade, the study of microbial communities has gained increasing research interest also driven by the recognition of the important role of these consortia in human health and disease. Metaproteomics, the analysis of the entire set of proteins from all microorganisms present in one ecosystem, has become a prominent technique for studying the relation between taxonomic diversity and functional profile of microbial communities. AREAS COVERED: The aim of this review is to address opportunities and challenges of metaproteomics from a computational perspective. Appealing to an audience of microbial ecologists and proteomic researchers alike, we provide an overview on state-of-the-art software and databases by which metaproteome data can be readily analyzed. Expert commentary: While tailored protein databases, combined search algorithms and iterative workflows are means to improve the identification yield, software tools for taxonomic and functional analysis are challenged by the vast amount of unannotated sequences in metaproteomics.
Meta-analysis of central and peripheral γ-aminobutyric acid levels in patients with unipolar and bipolar depression.

BACKGROUND: Many studies have measured central and peripheral γ-aminobutyric acid (GABA) levels in patients with depression. We performed a meta-analysis to provide an objective overview of GABA changes in those with unipolar or bipolar depression. METHODS: After a systematic database search, original data were extracted with the help of seminal authors to calculate standardized mean differences. We compared GABA levels between patients with current major depressive episodes and controls, between euthymic patients and controls, and in patients before and after treatment. We performed meta-regressions to explore the influence of demographic and clinical variables on GABA significant mean differences. RESULTS: For unipolar depression, central and peripheral GABA levels were diminished in currently depressed patients, but normal in euthymic patients, compared with the healthy controls. For bipolar disorder, GABA levels were diminished in medication-free patients, but seemed to be normalized in medicated patients, compared with the healthy controls. We found no significant association with demographic or clinical variables. LIMITATIONS: There was a great heterogeneity across studies, probably because of the substantial variation of clinical characteristics in the included samples. Many subanalyses were performed to assess how the diagnosis, medications, or the type of measurements of peripheral or central GABA levels may affect the main results. CONCLUSION: The GABA levels evolved differentially in patients with unipolar and bipolar disorders. Our results suggest that GABA levels could represent a biomarker of symptomatic states in patients with unipolar disorder and would be normalized by mood stabilizers in those with bipolar disorder.
Dyslipidemia, chronic inflammation, and subclinical atherosclerosis in children and adolescents infected with HIV: The PositHIVe Health Study.

HIV-infected children and adolescents may be at risk for cardiovascular disease due to chronic inflammation and exacerbation of risk factors. The aim of this study was as follows: 1) compare cardiovascular risk factors, chronic inflammation, and carotid intima-media thickness (IMTc) between the HIV and control groups; 2) determine the association of HIV and antiretroviral (ART) regimens with cardiovascular risk factors, chronic inflammation, and IMTc; and 3) identify variables associated with elevated IMTc. Cross-sectional analysis of 130 children and adolescents, 8-15 years of age, divided into HIV-infected (n = 65) and healthy control (n = 65) participants. Body fat, blood pressure, glycemia, insulin, and glycated hemoglobin, total cholesterol and fractions (LDL-C and HDL-C), triglycerides, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and the IMTc were measured. The results showed HIV-infected children and adolescents had higher levels of glycemia (87.9 vs. 75.9 mg.dL-1, p< 0.001), LDL-c (94.7 vs. 79.5 mg.dL-1, p = 0.010), triglycerides (101.2 vs. 61.6 mg.dL-1, p< 0.001), CRP (1.6 vs. 1.0 mg. L-1, p = 0.007), IL-6 (1.42 vs. 0.01 pg.mL-1, p< 0.001), TNF-α (0.49 vs. 0.01 pg.mL-1, p< 0.001), mean IMTc (0.526 vs. 0.499 mm, p = 0.009), and lower HDL-c (53.7 vs. 69.4 mg.dL-1, p< 0.001) compared to controls. Systolic blood pressure (β = 0.006, p = 0.004) and TNF-α (β = -0.033, p = 0.029) accounted for 16% of IMTc variability in HIV-infected children and adolescents. In patients using protease inhibitors-based ART, male gender (β = -0.186, p = 0.008), trunk body fat (β = -0.011, p = 0.006), glucose (β = 0.005, p = 0.046), and IL-6 (β = 0.017, p = 0.039) accounted for 28% of IMTc variability. HIV-infected children and adolescents may be at risk for premature atherosclerosis due to chronic inflammation and dyslipidemia. Interventions with the potential to improve lipid profile, mitigate inflammation, and reduce cardiovascular risk are needed.
The variome of pneumococcal virulence factors and regulators.

BACKGROUND: In recent years, the idea of a highly immunogenic protein-based vaccine to combat Streptococcus pneumoniae and its severe invasive infectious diseases has gained considerable interest. However, the target proteins to be included in a vaccine formulation have to accomplish several genetic and immunological characteristics, (such as conservation, distribution, immunogenicity and protective effect), in order to ensure its suitability and effectiveness. This study aimed to get comprehensive insights into the genomic organization, population distribution and genetic conservation of all pneumococcal surface-exposed proteins, genetic regulators and other virulence factors, whose important function and role in pathogenesis has been demonstrated or hypothesized. RESULTS: After retrieving the complete set of DNA and protein sequences reported in the databases GenBank, KEGG, VFDB, P2CS and Uniprot for pneumococcal strains whose genomes have been fully sequenced and annotated, a comprehensive bioinformatic analysis and systematic comparison has been performed for each virulence factor, stand-alone regulator and two-component regulatory system (TCS) encoded in the pan-genome of S. pneumoniae. A total of 25 S. pneumoniae strains, representing different pneumococcal phylogenetic lineages and serotypes, were considered. A set of 92 different genes and proteins were identified, classified and studied to construct a pan-genomic variability map (variome) for S. pneumoniae. Both, pneumococcal virulence factors and regulatory genes, were well-distributed in the pneumococcal genome and exhibited a conserved feature of genome organization, where replication and transcription are co-oriented. The analysis of the population distribution for each gene and protein showed that 49 of them are part of the core genome in pneumococci, while 43 belong to the accessory-genome. Estimating the genetic variability revealed that pneumolysin, enolase and Usp45 (SP_2216 in S. p. TIGR4) are the pneumococcal virulence factors with the highest conservation, while TCS08, TCS05, and TCS02 represent the most conserved pneumococcal genetic regulators. CONCLUSIONS: The results identified well-distributed and highly conserved pneumococcal virulence factors as well as regulators, representing promising candidates for a new generation of serotype-independent protein-based vaccine(s) to combat pneumococcal infections.
A pattern matching approach to the automatic selection of particles from low-contrast electron micrographs.

MOTIVATION: Structural information of macromolecular complexes provides key insights into the way they carry out their biological functions. Achieving high-resolution structural details with electron microscopy requires the identification of a large number (up to hundreds of thousands) of single particles from electron micrographs, which is a laborious task if it has to be manually done and constitutes a hurdle towards high-throughput. Automatic particle selection in micrographs is far from being settled and new and more robust algorithms are required to reduce the number of false positives and false negatives. RESULTS: In this article, we introduce an automatic particle picker that learns from the user the kind of particles he is interested in. Particle candidates are quickly and robustly classified as particles or non-particles. A number of new discriminative shape-related features as well as some statistical description of the image grey intensities are used to train two support vector machine classifiers. Experimental results demonstrate that the proposed method: (i) has a considerably low computational complexity and (ii) provides results better or comparable with previously reported methods at a fraction of their computing time. AVAILABILITY: The algorithm is fully implemented in the open-source Xmipp package and downloadable from http://xmipp.cnb.csic.es.
Relationship between Contrast Enhancement of the Perivascular Space in the Basal Ganglia and Endolymphatic Volume Ratio.

PURPOSE: We routinely obtain the endolymphatic hydrops (EH) image using heavily T2-weighted three dimensional-fluid attenuated inversion recovery (hT2w-3D-FLAIR) imaging at 4 hours after intravenous administration of a single-dose of gadolinium-based contrast media (IV-SD-GBCM). While repeating the examination, we speculated that the contrast enhancement of the perivascular space (PVS) in the basal ganglia might be related to the degree of EH. Therefore, the purpose of this study was to investigate the relationship between the endolymphatic volume ratio (%ELvolume) and the signal intensity of the PVS (SI-PVS). MATERIALS AND METHODS: In 20 patients with a suspicion of EH, a heavily T2-weighted 3D-turbo spin echo sequence for magnetic resonance (MR) cisternography (MRC) and an hT2w-3D-FLAIR as a positive perilymph image (PPI) were obtained at 4 hours after IV-SD-GBCM. The %ELvolume of the cochlea and the vestibule were measured on the previously reported HYDROPS2-Mi2 image. The PVS in the basal ganglia was segmented on MRC using a region-growing method. The PVS regions were copied and pasted onto the PPI, and the SI-PVS was measured. The larger value of the right and the left ears was employed as the %ELvolume, and the weighted average of both sides was employed as the SI-PVS. The correlation between the %ELvolume and the SI-PVS was evaluated. RESULT: There was a strong negative linear correlation between the %ELvolume of the cochlea and the SI-PVS (r = -0.743, P < 0.001); however, there was no significant correlation between the %ELvolume of the vestibule and the SI-PVS (r = -0.267, P = 0.256). CONCLUSION: There was a strong negative correlation between the cochlear %ELvolume and the SI-PVS. Contrast enhancement of PVS might be a biomarker of EH.
Prognosis of oesophageal adenocarcinoma and squamous cell carcinoma following surgery and no surgery in a nationwide Swedish cohort study.

OBJECTIVES: To assess the recent prognostic trends in oesophageal adenocarcinoma and oesophageal squamous cell carcinoma undergoing resectional surgery and no such surgery. Additionally, risk factors for death were assessed in each of these patient groups. DESIGN: Cohort study. SETTING: A population-based, nationwide study in Sweden. PARTICIPANTS: All patients diagnosed with oesophageal adenocarcinoma and oesophageal squamous cell carcinoma in Sweden from 1 January 1990 to 31 December 2013, with follow-up until 14 May 2017. OUTCOME MEASURES: Observed and relative (to the background population) 1-year , 3-year and 5-year survivals were analysed using life table method. Multivariable Cox regression provided HR with 95% CI for risk factors of death. RESULTS: Among 3794 patients with oesophageal adenocarcinoma and 4631 with oesophageal squamous cell carcinoma, 82% and 63% were men, respectively. From 1990-1994 to 2010-2013, the relative 5-year survival increased from 12% to 15% for oesophageal adenocarcinoma and from 9% to 12% for oesophageal squamous cell carcinoma. The corresponding survival following surgery increased from 27% to 45% in oesophageal adenocarcinoma and from 24% to 43% in oesophageal squamous cell carcinoma. In patients not undergoing surgery, the survival increased from 3% to 4% for oesophageal adenocarcinoma and from 3% to 6% for oesophageal squamous cell carcinoma. Women with oesophageal squamous cell carcinoma had better prognosis than men both following surgery (HR 0.71, 95% CI 0.61 to 0.83) and no surgery (HR 0.86, 95% CI 0.81 to 0.93). CONCLUSIONS: The prognosis has improved over calendar time both in oesophageal adenocarcinoma and oesophageal squamous cell carcinoma in Sweden that did and did not undergo surgery. Women appear to have better prognosis in oesophageal squamous cell carcinoma than men, independent of treatment.
University hospital status and surgeon volume and risk of reoperation following surgery for esophageal cancer.

PURPOSE: Centralization of surgery improves the survival following esophagectomy for cancer, but whether university hospital setting or surgeon volume influences the reoperation rates is unknown. We aimed to clarify whether hospital status or surgeon volume are associated with a risk of reoperation after esophagectomy. METHODS: Patients who underwent esophagectomy for esophageal cancer in 1987-2010 were identified from a population-based, nationwide Swedish cohort study. University hospital status and cumulative surgeon volume were analyzed in relation to risk of reoperation or death (the latter included to avoid competing risk errors) within 30 days of surgery. Multivariable logistic regression provided odds ratios (OR) with 95% confidence intervals (CI), adjusted for calendar period, age, sex, comorbidity, tumor histology, stage, neoadjuvant therapy, resection margin, surgeon volume, and hospital status. RESULTS: Among 1820 participants, 989 (54%) underwent esophagectomy in university hospitals and 271 (15%) died or were reoperated within 30 days of surgery. Non-university hospital status was associated with an increased risk of reoperation or death compared to university hospitals (adjusted OR 1.56, 95% CI 1.13-2.13). Regarding surgeon volume, the ORs were increased in the lower volume categories, but not statistically significant (OR 1.30, 95% CI 0.89-1.89 for surgeon volume <7 and OR 1.10, 95% CI 0.75-1.63 for surgeon volume 7-16, compared to surgeon volume >16). CONCLUSION: The risk of reoperation or death within 30 days of esophagectomy seems to be lower in university hospitals even after adjustment for surgeon volume and other potential confounders. These results support centralizing esophageal cancer patients to university hospitals.
Meta-analysis of health-related quality of life after minimally invasive versus open oesophagectomy for oesophageal cancer.

BACKGROUND: The aim of this systematic review and meta-analysis was to compare health-related quality of life (HRQoL) outcomes between minimally invasive and open oesophagectomy for cancer at different postoperative time points. METHODS: A search of PubMed (MEDLINE), Web of Science, Embase, Scopus, CINAHL and the Cochrane Library was performed for studies that compared open with minimally invasive oesophagectomy. A random-effects meta-analysis was conducted for studies that measured HRQoL scores using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-OES18 questionnaires. Mean differences (MDs) greater than 10 in scores were considered clinically relevant. Pooled effects of MDs with 95 per cent confidence intervals were estimated to assess statistical significance. RESULTS: Nine studies were included in the qualitative analysis, involving 1157 patients who had minimally invasive surgery and 907 patients who underwent open surgery. Minimally invasive surgery resulted in better scores for global quality of life (MD 11·61, 95 per cent c.i. 3·84 to 19·39), physical function (MD 11·88, 3·92 to 19·84), fatigue (MD -13·18, -17·59 to -8·76) and pain (MD -15·85, -20·45 to -11·24) compared with open surgery at 3 months after surgery. At 6 and 12 months, no significant differences remained. CONCLUSION: Patients report better global quality of life, physical function, fatigue and pain 3 months after minimally invasive surgery compared with open surgery. No such differences remain at longer follow-up of 6 and 12 months.