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Systematic Reviews Jul 2024The acute and long-term benefits of exercise training on cardiovascular health have been well established. The systematic review and meta-analysis aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The acute and long-term benefits of exercise training on cardiovascular health have been well established. The systematic review and meta-analysis aimed to systematically assess the effectiveness of exercise training on arterial stiffness and blood pressure among postmenopausal women with elevated blood pressure.
METHODS
A comprehensive search was conducted on PubMed, Embase, Web of Science, ProQuest, Cochrane Library, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov website from inception to September 30, 2023, to identify the randomized controlled trials (RCTs), which evaluated the effectiveness of exercise training on arterial stiffness and blood pressure in postmenopausal women. Standardized mean differences (SMD), weighted mean differences (WMD), and 95% confidence intervals (95% CIs) were calculated using random/fixed effects models. Quality assessment was performed using the modified Jadad scale and the Cochrane Risk of Bias Tool. Sensitivity analysis and subgroup analysis were conducted based on drug dosage, treatment duration, and age of administration to further explore potential heterogeneity. Funnel plots were performed to assess publication bias and Begg's regression test was carried out for funnel plot asymmetry.
RESULTS
Twenty-two RCTs involving 1978 participants were included in the quantitative analysis. The mean quality of eligible studies was 4.2 out of 7 based on the modified Jadad scale. The results indicated that exercise training had a significant effect on reducing brachial-ankle pulse wave velocity [MD = - 0.69, 95%CI (- 1.11, - 0.27), P = 0.001], decreasing augmentation index (AIx) [MD = - 6.00, 95%CI (- 6.39, - 5.61), P < 0.00001] and AIx normalized to a heart rate of 75 beats per minute (AIx@75%) [MD = - 7.01, 95%CI - 7.91 to - 6.12, P < 0.00001], lowering systolic blood pressure [MD = - 6.19, 95%CI - 9.24 to - 3.15, P < 0.0001], diastolic blood pressure [MD = - 3.57, 95%CI (- 6.10, - 1.03), P = 0.006) and pulse pressure [MD = - 8.52, 95%CI (- 16.27, - 0.76), P = 0.03]. Subgroup analysis revealed that baseline blood pressure levels had a large impact on the effect of exercise training.
CONCLUSIONS
The systematic review and meta-analysis suggested that exercise training may ameliorate arterial stiffness and reduce blood pressure in postmenopausal women with elevated blood pressure. However, the optimal mode of exercise training that improves arterial stiffness and blood pressure in this population requires further investigation.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021211268.
Topics: Humans; Vascular Stiffness; Postmenopause; Female; Blood Pressure; Exercise; Pulse Wave Analysis; Hypertension; Randomized Controlled Trials as Topic; Exercise Therapy
PubMed: 38956626
DOI: 10.1186/s13643-024-02589-y -
Microbial Cell Factories Jul 2024Carbonic anhydrase (CA) enzymes facilitate the reversible hydration of CO to bicarbonate ions and protons. Identifying efficient and robust CAs and expressing them in...
BACKGROUND
Carbonic anhydrase (CA) enzymes facilitate the reversible hydration of CO to bicarbonate ions and protons. Identifying efficient and robust CAs and expressing them in model host cells, such as Escherichia coli, enables more efficient engineering of these enzymes for industrial CO capture. However, expression of CAs in E. coli is challenging due to the possible formation of insoluble protein aggregates, or inclusion bodies. This makes the production of soluble and active CA protein a prerequisite for downstream applications.
RESULTS
In this study, we streamlined the process of CA expression by selecting seven top CA candidates and used two bioinformatic tools to predict their solubility for expression in E. coli. The prediction results place these enzymes in two categories: low and high solubility. Our expression of high solubility score CAs (namely CA5-SspCA, CA6-SazCAtrunc, CA7-PabCA and CA8-PhoCA) led to significantly higher protein yields (5 to 75 mg purified protein per liter) in flask cultures, indicating a strong correlation between the solubility prediction score and protein expression yields. Furthermore, phylogenetic tree analysis demonstrated CA class-specific clustering patterns for protein solubility and production yields. Unexpectedly, we also found that the unique N-terminal, 11-amino acid segment found after the signal sequence (not present in its homologs), was essential for CA6-SazCA activity.
CONCLUSIONS
Overall, this work demonstrated that protein solubility prediction, phylogenetic tree analysis, and experimental validation are potent tools for identifying top CA candidates and then producing soluble, active forms of these enzymes in E. coli. The comprehensive approaches we report here should be extendable to the expression of other heterogeneous proteins in E. coli.
Topics: Escherichia coli; Carbonic Anhydrases; Computational Biology; Solubility; Phylogeny; Recombinant Proteins; Carbon Dioxide
PubMed: 38956607
DOI: 10.1186/s12934-024-02463-5 -
Genome Biology Jul 2024Computational cell type deconvolution enables the estimation of cell type abundance from bulk tissues and is important for understanding tissue microenviroment,...
BACKGROUND
Computational cell type deconvolution enables the estimation of cell type abundance from bulk tissues and is important for understanding tissue microenviroment, especially in tumor tissues. With rapid development of deconvolution methods, many benchmarking studies have been published aiming for a comprehensive evaluation for these methods. Benchmarking studies rely on cell-type resolved single-cell RNA-seq data to create simulated pseudobulk datasets by adding individual cells-types in controlled proportions.
RESULTS
In our work, we show that the standard application of this approach, which uses randomly selected single cells, regardless of the intrinsic difference between them, generates synthetic bulk expression values that lack appropriate biological variance. We demonstrate why and how the current bulk simulation pipeline with random cells is unrealistic and propose a heterogeneous simulation strategy as a solution. The heterogeneously simulated bulk samples match up with the variance observed in real bulk datasets and therefore provide concrete benefits for benchmarking in several ways. We demonstrate that conceptual classes of deconvolution methods differ dramatically in their robustness to heterogeneity with reference-free methods performing particularly poorly. For regression-based methods, the heterogeneous simulation provides an explicit framework to disentangle the contributions of reference construction and regression methods to performance. Finally, we perform an extensive benchmark of diverse methods across eight different datasets and find BayesPrism and a hybrid MuSiC/CIBERSORTx approach to be the top performers.
CONCLUSIONS
Our heterogeneous bulk simulation method and the entire benchmarking framework is implemented in a user friendly package https://github.com/humengying0907/deconvBenchmarking and https://doi.org/10.5281/zenodo.8206516 , enabling further developments in deconvolution methods.
Topics: Benchmarking; Single-Cell Analysis; Humans; Computer Simulation; RNA-Seq; Computational Biology
PubMed: 38956606
DOI: 10.1186/s13059-024-03292-w -
BMC Public Health Jul 2024The aim of this review was to investigate the impact of short message service (SMS)-based interventions on childhood and adolescent vaccine coverage and timeliness.
BACKGROUND
The aim of this review was to investigate the impact of short message service (SMS)-based interventions on childhood and adolescent vaccine coverage and timeliness.
METHODS
A pre-defined search strategy was used to identify all relevant publications up until July 2022 from electronic databases. Reports of randomised trials written in English and involving children and adolescents less than 18 years old were included. The review was conducted in accordance with PRISMA guidelines.
RESULTS
Thirty randomised trials were identified. Most trials were conducted in high-income countries. There was marked heterogeneity between studies. SMS-based interventions were associated with small to moderate improvements in vaccine coverage and timeliness compared to no SMS reminder. Reminders with embedded education or which were combined with monetary incentives performed better than simple reminders in some settings.
CONCLUSION
Some SMS-based interventions appear effective for improving child vaccine coverage and timeliness in some settings. Future studies should focus on identifying which features of SMS-based strategies, including the message content and timing, are determinants of effectiveness.
Topics: Humans; Text Messaging; Child; Adolescent; Reminder Systems; Vaccination Coverage; Randomized Controlled Trials as Topic; Child, Preschool
PubMed: 38956527
DOI: 10.1186/s12889-024-18900-4 -
BMC Medical Genomics Jul 2024Autosomal recessive non-syndromic hearing loss (NSHL) and cone dystrophies (CODs) are highly genetically and phenotypically heterogeneous disorders. In this study, we...
Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia.
BACKGROUND
Autosomal recessive non-syndromic hearing loss (NSHL) and cone dystrophies (CODs) are highly genetically and phenotypically heterogeneous disorders. In this study, we applied the whole exome sequencing (WES) to find the cause of HL and COD in an Iranian consanguineous family with three affected individuals.
METHODS
Three members from an Iranian consanguineous family who were suffering from NSHL and visual impairment were ascertained in this study. Comprehensive clinical evaluations and genetic analysis followed by bioinformatic and co-segregation studies were performed to diagnose the cause of these phenotypes. Data were collected from 2020 to 2022.
RESULTS
All cases showed congenital bilateral NSHL, decreased visual acuity, poor color discrimination, photophobia and macular atrophy. Moreover, cornea, iris and anterior vitreous were within normal limit in both eyes, decreased foveal sensitivity, central scotoma and generalized depression of visual field were seen in three cases. WES results showed two variants, a novel null variant (p.Trp548Ter) in the PDE6C gene causing COD type 4 (Achromatopsia) and a previously reported variant (p.Ile84Thr) in the PDZD7 gene causing NSHL. Both variants were found in the cis configuration on chromosome 10 with a genetic distance of about 8.3 cM, leading to their co-inheritance. However, two diseases could appear independently in subsequent generations due to crossover during meiosis.
CONCLUSIONS
Here, we could successfully determine the etiology of a seemingly complex phenotype in two adjacent genes. We identified a novel variant in the PDE6C gene, related to achromatopsia. Interestingly, this variant could cooperatively cause visual disorders: cone dystrophy and cone-rod dystrophy.
Topics: Humans; Color Vision Defects; Cyclic Nucleotide Phosphodiesterases, Type 6; Male; Female; Pedigree; Exome Sequencing; Adult; Hearing Loss; Mutation; Consanguinity; Child; Iran; Phenotype; Eye Proteins
PubMed: 38956522
DOI: 10.1186/s12920-024-01942-3 -
BMC Anesthesiology Jul 2024As a new type of intravenous anesthetic, ciprofol has the advantages of fast onset of action, fast recovery and high clearance rate. This study aimed to investigate the... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparison of the efficacy and safety of ciprofol and propofol in sedating patients in the operating room and outside the operating room: a meta-analysis and systematic review.
BACKGROUND
As a new type of intravenous anesthetic, ciprofol has the advantages of fast onset of action, fast recovery and high clearance rate. This study aimed to investigate the effectiveness and safety of ciprofol versus traditional propofol for anesthesia and sedation in and out of the operating room.
METHODS
We searched the literature in PubMed, Web of Science, Cochrane Library, and Embase databases from January 2021 to December 2023. All clinical studies comparing the sedative effects of propofol and ciprofol, both inside and outside the operating room, were included in our trial. The main outcome measures were induction time and incidence of injection-site pain. Data are merged using risk ratio and standardized mean difference with 95% confidence interval. Subgroup analysis, meta-regression, sensitivity analysis, and publication bias were performed. The study protocol was prospectively registered with PROSPERO (CRD42023447747).
RESULTS
A total of 15 randomized, controlled trials involving 2002 patients were included in this study. Compared with propofol, ciprofol has a longer induction time in the operating room but a shorter induction time in non-operating room settings. Ciprofol can effectively reduce the risk of injection-site pain and respiratory depression both inside and outside the operating room. In addition, the risk of drug-related hypotension induced with ciprofol in the operating room is lower, but the awakening time is also longer. Meta-regression analysis showed that neither age nor BMI were potential sources of heterogeneity. Funnel plot, egger and begg tests showed no significant publication bias. Sensitivity analyzes indicate that our results are robust and reliable.
CONCLUSION
Ciprofol has absolute advantages in reducing the risk of injection-site pain and respiratory depression, both in and outside operating room. Intraoperative use of ciprofol reduces the risk of drug-related hypotension and may also reduce the risk of intraoperative physical movements. However, ciprofol may have longer induction and awakening time than propofol.
Topics: Propofol; Humans; Operating Rooms; Anesthetics, Intravenous; Hypnotics and Sedatives; Randomized Controlled Trials as Topic
PubMed: 38956515
DOI: 10.1186/s12871-024-02609-3 -
Diagnosis of cystic fibrosis: a high heterogeneity of symptoms and genotypes in a Brazil population.BMC Pediatrics Jul 2024In highly multiracial populations with inadequate newborn screening, knowledge of the various phenotypic presentations of Cystic Fibrosis (CF) can help reach an early...
INTRODUCTION
In highly multiracial populations with inadequate newborn screening, knowledge of the various phenotypic presentations of Cystic Fibrosis (CF) can help reach an early diagnosis. This study aims to describe phenotypes and genotypes at the time of CF diagnosis in a state in the Northeast Region of Brazil.
METHODS
Retrospective cross-sectional study. Clinical data were extracted from the medical records of CF patients. Clinical, laboratory, and genotypic characteristics were described for patients admitted to a tertiary referral center between 2007 and 2021.
RESULTS
Fifty-eight (58) patients were included in the study, 53.5% of whom were diagnosed through clinical suspicion. The median age at diagnosis was 4.7 months (IQR: 1.5-14.8 months). Five patients had false-negative results in the newborn screening. Faltering growth was the most frequent clinical manifestation. Bronchiectasis and a history of pneumonia predominated in those older than ten, while thinness, underweight, and electrolyte imbalances were more frequent in children under two. Sequencing of the CFTR gene identified 27 genotypes, with at least one class I-III variant in all patients, and nine variants that are rare, previously undescribed, or have uncertain significance (619delA, T12991, K162Q, 3195del6, 1678del > T, 124del123bp, 3121-3113 A > T). The most frequent alleles were p.Phe508del, p.Gly542*, p.Arg334Trp, and p.Ser549Arg.
CONCLUSIONS
Malnutrition and electrolyte imbalances were the most frequent phenotypes for children < 2 years and were associated with genotypes including 2 class I-III variants. Rare and previously undescribed variants were identified. The p.Gly542*, p.Arg334Trp, and p.Ser549Arg alleles were among the most frequent variants in this population.
Topics: Humans; Cystic Fibrosis; Brazil; Cross-Sectional Studies; Retrospective Studies; Male; Female; Infant; Genotype; Cystic Fibrosis Transmembrane Conductance Regulator; Phenotype; Infant, Newborn; Neonatal Screening; Child, Preschool; Mutation
PubMed: 38956483
DOI: 10.1186/s12887-024-04891-z -
Scientific Reports Jul 2024The intestinal epithelium dynamically controls cell cycle, yet no experimental platform exists for directly analyzing cell cycle phases in non-immortalized human...
The intestinal epithelium dynamically controls cell cycle, yet no experimental platform exists for directly analyzing cell cycle phases in non-immortalized human intestinal epithelial cells (IECs). Here, we present two reporters and a complete platform for analyzing cell cycle phases in live primary human IECs. We interrogate the transcriptional identity of IECs grown on soft collagen, develop two fluorescent cell cycle reporter IEC lines, design and 3D print a collagen press to make chamber slides for optimal imaging while supporting primary human IEC growth, live image cell cycle dynamics, then assemble a computational pipeline building upon free-to-use programs for semi-automated analysis of cell cycle phases. The PIP-FUCCI construct allows for assigning cell cycle phase from a single image of living cells, and our PIP-H2A construct allows for semi-automated direct quantification of cell cycle phase lengths using our publicly available computational pipeline. Treating PIP-FUCCI IECs with oligomycin demonstrates that inhibiting mitochondrial respiration lengthens G1 phase, and PIP-H2A cells allow us to measure that oligomycin differentially lengthens S and G2/M phases across heterogeneous IECs. These platforms provide opportunities for future studies on pharmaceutical effects on the intestinal epithelium, cell cycle regulation, and more.
Topics: Humans; Epithelial Cells; Intestinal Mucosa; Cell Cycle; Oligomycins; Cells, Cultured
PubMed: 38956443
DOI: 10.1038/s41598-024-66042-9 -
World Journal of Surgery Jul 2024Emergency presentations make up a large proportion of a general surgeon's workload. Patients who have emergency surgery carry a higher rate of mortality and...
BACKGROUND
Emergency presentations make up a large proportion of a general surgeon's workload. Patients who have emergency surgery carry a higher rate of mortality and complications. We aim to review the impact of surgical subspecialization on patients following upper gastrointestinal (UGI) emergency surgery.
METHODS
A systematic search of Ovid Embase, Ovid MEDLINE, and Cochrane databases using a predefined search strategy was completed reviewing studies published from 1st of January 1990 to August 27, 2023. The study was prospectively registered with PROSPERO (CRD42022359326). Studies were reviewed for the following outcomes: 30-day mortality, in-hospital mortality, conversion to open, length of stay, return to theater, and readmission.
RESULTS
Of 5181 studies, 24 articles were selected for full text review. Of these, seven were eligible and included in this study. There was a statistically significant improvement in 30-day mortality favoring UGI specialists (OR 0.71 [95% CI 0.55-0.92 and p = 0.009]) and in-hospital mortality (OR 0.29 [95% CI 0.14-0.60 and p = 0009]). There was a high degree of study heterogeneity in 30-day mortality; however, a low degree of heterogeneity within in-hospital mortality. There was no statistical significance when considering conversion to open and insufficient data to allow meta-analysis for return to theater or readmission rates.
CONCLUSION
In emergency UGI surgery, there was improved 30-day and in-hospital mortality for UGI specialists. Therefore, surgeons should consider early involvement of a subspecialist team to improve patient outcomes.
PubMed: 38956401
DOI: 10.1002/wjs.12267 -
Nature Immunology Jul 2024Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a...
Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to dissect the heterogeneity of NK cells. We identified three prominent NK cell subsets in healthy human blood: NK1, NK2 and NK3, further differentiated into six distinct subgroups. Our findings delineate the molecular characteristics, key transcription factors, biological functions, metabolic traits and cytokine responses of each subgroup. These data also suggest two separate ontogenetic origins for NK cells, leading to divergent transcriptional trajectories. Furthermore, we analyzed the distribution of NK cell subsets in the lung, tonsils and intraepithelial lymphocytes isolated from healthy individuals and in 22 tumor types. This standardized terminology aims at fostering clarity and consistency in future research, thereby improving cross-study comparisons.
PubMed: 38956378
DOI: 10.1038/s41590-024-01883-0