Abstract
The accurate identification and description of the genes in the human and mouse genomes is a fundamental requirement for high quality analysis of data informing both genome biology and ...clinical genomics. Over the last 15 years, the GENCODE consortium has been producing reference quality gene annotations to provide this foundational resource. The GENCODE consortium includes both experimental and computational biology groups who work together to improve and extend the GENCODE gene annotation. Specifically, we generate primary data, create bioinformatics tools and provide analysis to support the work of expert manual gene annotators and automated gene annotation pipelines. In addition, manual and computational annotation workflows use any and all publicly available data and analysis, along with the research literature to identify and characterise gene loci to the highest standard. GENCODE gene annotations are accessible via the Ensembl and UCSC Genome Browsers, the Ensembl FTP site, Ensembl Biomart, Ensembl Perl and REST APIs as well as https://www.gencodegenes.org.
Abstract
The GENCODE project annotates human and mouse genes and transcripts supported by experimental data with high accuracy, providing a foundational resource that supports genome biology and ...clinical genomics. GENCODE annotation processes make use of primary data and bioinformatic tools and analysis generated both within the consortium and externally to support the creation of transcript structures and the determination of their function. Here, we present improvements to our annotation infrastructure, bioinformatics tools, and analysis, and the advances they support in the annotation of the human and mouse genomes including: the completion of first pass manual annotation for the mouse reference genome; targeted improvements to the annotation of genes associated with SARS-CoV-2 infection; collaborative projects to achieve convergence across reference annotation databases for the annotation of human and mouse protein-coding genes; and the first GENCODE manually supervised automated annotation of lncRNAs. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes.org.
The role of alternative splicing is one of the great unanswered questions in cellular biology. There is strong evidence for alternative splicing at the transcript level, and transcriptomics ...experiments show that many splice events are tissue specific. It has been suggested that alternative splicing evolved in order to remodel tissue-specific protein-protein networks. Here we investigated the evidence for tissue-specific splicing among splice isoforms detected in a large-scale proteomics analysis. Although the data supporting alternative splicing is limited at the protein level, clear patterns emerged among the small numbers of alternative splice events that we could detect in the proteomics data. More than a third of these splice events were tissue-specific and most were ancient: over 95% of splice events that were tissue-specific in both proteomics and RNAseq analyses evolved prior to the ancestors of lobe-finned fish, at least 400 million years ago. By way of contrast, three in four alternative exons in the human gene set arose in the primate lineage, so our results cannot be extrapolated to the whole genome. Tissue-specific alternative protein forms in the proteomics analysis were particularly abundant in nervous and muscle tissues and their genes had roles related to the cytoskeleton and either the structure of muscle fibres or cell-cell connections. Our results suggest that this conserved tissue-specific alternative splicing may have played a role in the development of the vertebrate brain and heart.
To gather evidence on the effectiveness and safety of qigong, tai chi, and yoga to modulate symptoms associated with chronic respiratory diseases.
A search of systematic reviews was conducted in ...CINHAL, Embase, PubMed, PsycINFO, SPORTDiscus, and the Cochrane Library from inception to November 2022. Systematic reviews with meta-analyses investigating physical and psychological measures were eligible. The methodological quality of systematic reviews (AMSTAR-2), the spin of information in abstracts, and the overlap of primary studies were explored.
Twenty-seven systematic reviews involving 37 000 participants, 146 studies, and 150 meta-analyses were included. Reviews investigated asthma (n = 4) and chronic obstructive pulmonary disease (COPD) (n = 23). Most reviews discussed their findings without considering the risk of bias of primary studies. The overlap ranged between slight (5%) and very high (35%). Yoga was better than control interventions to improve symptoms related with asthma. In adults with COPD, qigong improved dyspnoea, exercise endurance, lung function, and quality of life, while tai chi and yoga increased exercise endurance.
The impact of yoga on symptoms associated with asthma varied depending on the lung function parameter and the control group. Qigong, tai chi, and yoga could be effective to improve COPD-related symptoms, especially exercise endurance.
IMPLICATIONS FOR REHABILITATION
Qigong, tai chi, and yoga could be effective to improve symptoms associated with chronic obstructive pulmonary disease.
Mind-body exercises promote self-care management and can be individually tailored.
Due to no adverse effects, these interventions can be endorsed for rehabilitation as they appear to yield benefits
Exercise therapy is the first-line intervention recommended for those with chronic musculoskeletal pain (CMP). Smartphone technologies (mHealth) represent a feasible means for exercise prescription ...and individualization. This systematic review with meta-analysis aimed to identify factors associated with changes in pain and function following mHealth-based exercise therapy in patients with CMP. CINAHL (via EBSCOhost), Embase, PubMed, Scopus, and SPORTdiscus were searched from inception to February 2023. Observational and controlled clinical trials with correlation or regression analysis of factors associated with the effect of mHealth exercise interventions on pain and function were included. The risk of bias, completeness of interventions, spin of information, and certainty in the evidence were evaluated. Eight studies with 51,755 participants were included. Reduced pain intensity after intervention was associated with higher physical function: r (95% CI) = −0.55 (−0.67 to −0.41); I2 = 86%, Tau2 = 0.02; p < 0.01. Meta-regression identified the Body Mass Index (BMI), exercise dose, and completion rate as potential moderators between changes in pain and physical function following mHealth exercise therapy. No association was found between pain and anxiety: r (95% CI) = 0.15 (−0.08 to 0.37); I2 = 87%, Tau2 = 0.02; p = 0.19. Very low certainty in the evidence was observed due to serious concerns regarding the risk of bias, inconsistency, and indirectness. The limited available evidence detracts from the clinical interpretation of the findings.
Three-phase induction motors are widely used in the industrial field due to their low cost and robustness; therefore, it is essential to continuously develop new proposals that improve their behavior ...and response in applications where speed control is required. This paper proposes the development of an intelligent controller programmed in a PLC and interconnected with a three-phase induction motor through a VFD. The novel intelligent controller bases its operation on the LAMDA algorithm, which acts as a decision-making system based on the state of the error with respect to the speed reference and its derivative, obtaining a closed-loop controller. In addition, the VFD receives commands from the PLC to operate the motor at a constant voltage-frequency ratio in which flux remains constant. The proposed controller has been validated in two study cases: i) reference changes and ii) rejection of disturbances. The results obtained are promising and show a good performance of the LAMDA controller when compared qualitatively and quantitatively with the controller most commonly used in industrial systems, such as PID, and controllers with similar characteristics, such as fuzzy, based on Mamdani and Takagi-Sugeno inference. Doi: 10.28991/ESJ-2023-07-03-01 Full Text: PDF
Clinical variant interpretation is highly dependent on the choice of reference transcript. Although the longest transcript has traditionally been chosen as the reference, APPRIS principal and MANE ...Select transcripts, biologically supported reference sequences, are now available. In this study, we show that MANE Select and APPRIS principal transcripts are the best reference transcripts for clinical variation. APPRIS principal and MANE Select transcripts capture almost all ClinVar pathogenic variants, and they are particularly powerful over the 94% of coding genes in which they agree. We find that a vanishingly small number of ClinVar pathogenic variants affect alternative protein products. Alternative isoforms that are likely to be clinically relevant can be predicted using TRIFID scores, the highest scoring alternative transcripts are almost 700 times more likely to house pathogenic variants. We believe that APPRIS, MANE and TRIFID are essential tools for clinical variant interpretation.
In lung cancer immunotherapy, biomarkers to guide clinical decisions are limited. We now explore whether the detailed immunophenotyping of circulating peripheral blood mononuclear cells (PBMCs) can ...predict the efficacy of anti-PD-1 immunotherapy in patients with advanced non-small-cell lung cancer (NSCLC). We determined 107 PBMCs subpopulations in a prospective cohort of NSCLC patients before starting single-agent anti-PD-1 immunotherapy (study group), analyzed by flow cytometry. As a control group, we studied patients with advanced malignancies before initiating non-immunotherapy treatment. The frequency of PBMCs was correlated with treatment outcome. Patients were categorized as having either high or low expression for each biomarker, defined as those above the 55th or below the 45th percentile of the overall marker expression within the cohort. In the study group, three subpopulations were associated with significant differences in outcome: high pretreatment levels of circulating CD4+CCR9+, CD4+CCR10+, or CD8+CXCR4+ T cells correlated with poorer overall survival (15.7 vs. 35.9 months, HR 0.16, p = 0.003; 22.0 vs. NR months, HR 0.10, p = 0.003, and 22.0 vs. NR months, HR 0.29, p = 0.02). These differences were specific to immunotherapy-treated patients. High baseline levels of circulating T cell subpopulations related to tissue lymphocyte recruitment are associated with poorer outcomes of immunotherapy-treated advanced NSCLC patients.
Current evidence for widespread hyperalgesia in non-specific neck pain (NSNP) is unclear. It is currently recommended to group NSNP patients according to pain-provoking movements. The aim of this ...study was to investigate local and widespread pain sensitivity in females with unilateral NSNP that is reproducible during passive neck rotation compared with matched controls, and to compare the side specific effect of pain location on pressure pain sensitivity among females with unilateral NSNP. Thirty-six females with unilateral NSNP evoked during passive ipsilateral (
= 20) or contralateral (
= 16) rotation toward the painful side were compared with 20 controls. Participants reported their pain intensity at rest and during passive neck rotation and completed the Neck Disability Index. Pressure pain thresholds (PPTs) were assessed bilaterally over the anterior scalene; the sternocleidomastoid; the levator scapulae; lateral to the spinous process of C6; the median, ulnar, and radial nerves; and the tibialis anterior. The ANOVA revealed lower PPTs in females with unilateral NSNP compared with the controls (all at
< 0.001), but no differences were found between the sides, nor was there any Group × side interaction. Among females with NSNP, those with higher pain intensity during ipsilateral rotation toward the painful side showed lower PPTs over the anterior scalene, median nerve, ulnar nerve, and tibialis anterior (all,
< 0.05) than females with higher pain intensity during contralateral rotation toward the painful side. These findings demonstrated bilateral local and widespread pressure pain hyperalgesia in females with unilateral NSNP that was reproducible during passive neck rotation compared with controls. There was no side specific effect of pain location on PPTs among females with unilateral NSNP.
Abstract Objective The purpose of this study was to measure the immediate differences in craniocervical posture and pressure pain threshold of the greater occipital (GO) nerve in asymptomatic ...subjects with a history of having used orthodontics, after intervention by a suboccipital muscle inhibition (SMI) technique. Methods This was a randomized, single-blind, clinical study with a sample of 24 subjects (21 ± 1.78 years) that were divided into an experimental group (n = 12) who underwent the SMI technique and a sham group (n = 12) who underwent a sham (placebo) intervention. The sitting and standing craniovertebral angle and the pressure pain threshold of the GO nerve in both hemispheres were measured. Results The between-group comparison of the sample indicated that individuals subjected to the SMI technique showed a statistically significant increase in the craniovertebral angle in both the sitting ( P < .001, F1,22 = 102.09, R2 = 0.82) and the standing ( P < .001, F1,22 = 21.42, R2 = 0.56) positions and in the GO nerve pressure pain threshold in the nondominant hemisphere ( P = .014, F1,22 = 7.06, R2 = 0.24). There were no statistically significant differences observed for the GO nerve mechanosensitivity in the dominant side ( P = .202). Conclusion Suboccipital muscle inhibition technique immediately improved the position of the head with the subject seated and standing, the clinical effect size being large in the former case. It also immediately decreased the mechanosensitivity of the GO nerve in the nondominant hemisphere, although the effect size was small.
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