Tag: pubmed

Pharmacogenomics J. 2022 Oct 15. doi: 10.1038/s41397-022-00290-8. Online ahead of print.

ABSTRACT

Psoriatic arthritis (PsA) is a heterogeneous chronic musculoskeletal disease, affecting up to 30% of people with psoriasis. Research into PsA pathogenesis has led to the development of targeted therapies, including Tumor Necrosis Factor inhibitors (TNF-i). Good response is only achieved by ~60% of patients leading to ‘trial and error’ drug management approaches, adverse reactions and increasing healthcare costs. Robust and well-validated biomarker identification, and subsequent development of sensitive and specific assays, would facilitate the implementation of a stratified approach into clinical care. This review will summarise potential genetic biomarkers for TNF-i (adalimumab, etanercept and infliximab) response that have been reported to date. It will also comment upon the importance of managing clinical confounders when understanding drug response prediction. Variants in multiple gene regions including TNF-A, FCGR2A, TNFAIP3, TNFR1/TNFR1A/TNFRSF1A, TRAIL-R1/TNFRSF10A, FCGR3A have been reported to correlate with TNF-i response at various levels of statistical significance in patients with PsA. However, results were often from heterogenous and underpowered cohorts and none are currently implemented into clinical practice. External validation of genetic biomarkers in large, well-documented cohorts is required, and assessment of the predictive value of combining multiple genetic biomarkers with clinical measures is essential to clinically embed pharmacogenomics into PsA drug management.

PMID:36243888 | DOI:10.1038/s41397-022-00290-8

Sci Rep. 2022 Oct 15;12(1):17327. doi: 10.1038/s41598-022-22243-8.

ABSTRACT

Modelling extreme values distributions, such as wave height time series where the higher waves are much less frequent than the lower ones, has been tackled from the point of view of the Peak-Over-Threshold (POT) methodologies, where modelling is based on those values higher than a threshold. This threshold is usually predefined by the user, while the rest of values are ignored. In this paper, we propose a new method to estimate the distribution of the complete time series, including both extreme and regular values. This methodology assumes that extreme values time series can be modelled by a normal distribution in a combination of a uniform one. The resulting theoretical distribution is then used to fix the threshold for the POT methodology. The methodology is tested in nine real-world time series collected in the Gulf of Alaska, Puerto Rico and Gibraltar (Spain), which are provided by the National Data Buoy Center (USA) and Puertos del Estado (Spain). By using the Kolmogorov-Smirnov statistical test, the results confirm that the time series can be modelled with this type of mixed distribution. Based on this, the return values and the confidence intervals for wave height in different periods of time are also calculated.

PMID:36243880 | DOI:10.1038/s41598-022-22243-8

Sci Rep. 2022 Oct 15;12(1):17303. doi: 10.1038/s41598-022-21458-z.

ABSTRACT

Hypertension represents the main risk factor for the onset of cardiovascular diseases. Pharmacological treatments to control hypertension have been associated with new treatments involving physical activity and/or the intake of natural components (nutraceuticals). We here report the effects produced by a combination of a natural component (catechins) and a moderate exercise program on the development of hypertension in spontaneous hypertensive rats compared with those of each individual treatment. Arterial blood pressure and heart rate were measured with a non-invasive method in 28 rats randomly assigned to four groups: rats subjected to moderate physical exercise; rats with a catechins-enriched diet; rats subjected to moderate physical exercise combined with a catechins-enriched diet; control, untreated-rats left to age. All treatments were applied for 6 weeks. The statistical analysis revealed that the three treatments significantly reduced the weekly increase in arterial blood pressure observed in control rats (SBP, P < 0.0001; DBP, P = 0.005). However, the reduction of arterial blood pressure induced by combined treatments was not higher than that induced by the single treatment, but more prolonged. All treatments showed strong antioxidative properties. Our data show that physical activity and a diet enriched with catechins individually have an important hypotensive effect, while the association did not produce a higher hypotensive effect than the single treatment, even if it was able to decrease blood pressure for a longer time. These findings have important implications for developing a protocol to apply in novel hypertension prevention procedures.

PMID:36243879 | DOI:10.1038/s41598-022-21458-z

Sci Data. 2022 Oct 15;9(1):628. doi: 10.1038/s41597-022-01732-5.

ABSTRACT

We present an integrated database suitable for the investigation of the economic development of countries by using the Economic Fitness and Complexity framework. Firstly, we implement machine learning techniques to reconstruct the export flow of services and we combine them to the export flow of the physical goods, generating a complete view of the international market, denoted the Integrated database. Successively, we support the technical quality of the database by computing the main metrics of the Economic Fitness and Complexity framework: (i) we build a statistically validated network of economic activities, where preferred paths of development and clusters of High-Tech industries naturally emerge; (ii) we evaluate the Economic Fitness, an algorithmic assessment of the competitiveness of countries, removing the unexpected misbehaviour of economies under-represented by the sole consideration of the export of the physical goods.

PMID:36243877 | DOI:10.1038/s41597-022-01732-5

Syst Rev. 2022 Oct 15;11(1):220. doi: 10.1186/s13643-022-02090-4.

ABSTRACT

BACKGROUND: Suboptimal blood pressure control among people living with diabetes mellitus (DM) is one of the primary causes of cardiovascular complications and death in sub-Saharan Africa (SSA). However, there is a paucity of evidence on the prevalence and associated factors of suboptimal blood pressure control in SSA. Therefore, this review aimed to estimate its pooled prevalence and associated factors among people living with DM in SSA. METHODS: We systematically searched PubMed, African Journals OnLine, HINARI, ScienceDirect, Google Scholar, and direct Google to access observational studies conducted in SSA. Microsoft Excel spreadsheet was used to extract the data, which was exported into STATA/MP version 16.0 for further analyses. Heterogeneity across studies was checked using Cochran’s Q test statistics and I² test, and small study effect was checked using Funnel plot symmetry and Egger’s statistical test at a 5% significant level. A random-effects model was used to estimate the pooled prevalence and associated factors of suboptimal blood pressure control at a 95% confidence interval (CI) and significance level of p < 0.05.

RESULTS: Of the 7329 articles retrieved, 21 articles were eligible for the meta-analysis. After performing random-effects model, the pooled prevalence of suboptimal blood pressure control was 69.8% (95% CI: 63.43, 76.25%). Poor adherence to antihypertensive treatment (OR = 1.7; 95% CI: 1.03-2.80, I² = 0.0%, p = 0.531) and overweight (OR = 2.4, 95% CI: 1.57-3.68, I² = 0.00%, p = 0.47) were significantly associated with suboptimal blood pressure control.

CONCLUSIONS: The prevalence of suboptimal blood pressure control among diabetic patients in SSA was high, and poor adherence to antihypertensive treatment and overweight were significantly associated with suboptimal blood pressure control. Hence, there is an urgent need for initiatives to improve and control hypertension, and preventive measures should concentrate on modifiable risk factors.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020187901.

PMID:36243876 | DOI:10.1186/s13643-022-02090-4

Clin Epigenetics. 2022 Oct 15;14(1):129. doi: 10.1186/s13148-022-01348-x.

ABSTRACT

BACKGROUND: Alterations in the epigenome are a risk factor in multiple disease states. We have demonstrated in the past that disruption of the epigenome during early pregnancy or periconception, as demonstrated by altered methylation, may be associated with both assisted reproductive technology and undesirable clinical outcomes at birth, such as low birth weight. We have previously defined this altered methylation, calculated based on statistical upper and lower limits of outlier CpGs compared to the population, as an ‘outlier methylation phenotype’ (OMP). Our aim in this study was to determine whether children thus identified as possessing an OMP at birth by DNA methylation in cord blood persist as outliers in early childhood based on salivary DNA methylation.

RESULTS: A total of 31 children were included in the analysis. Among 24 children for whom both cord blood DNA and salivary DNA were available, DNA methylation patterns, analyzed using the Illumina Infinium MethylationEPIC BeadChip (850 K), between cord blood at birth and saliva in childhood at age 6-12 years remain stable (R² range 0.89-0.97). At birth, three out of 28 children demonstrated an OMP in multiple cord blood datasets and hierarchical clustering. Overall DNA methylation among all three OMP children identified as outliers at birth was remarkably stable (individual R² 0.908, 0.92, 0.915), even when only outlier CpG sites were considered (R² 0.694, 0.738, 0.828).

CONCLUSIONS: DNA methylation signatures in cord blood remain stable over time as demonstrated by a strong correlation with epigenetic salivary signatures in childhood. Future work is planned to identify whether a clinical phenotype is associated with OMP and, if so, could undesirable clinical outcomes in childhood and adulthood be predicted at birth.

PMID:36243864 | DOI:10.1186/s13148-022-01348-x

Ir J Med Sci. 2022 Oct 16. doi: 10.1007/s11845-022-03189-2. Online ahead of print.

ABSTRACT

AIM: This study aimed to investigate the effectiveness of disposable continuous positive airway pressure (DCPAP) system in decreasing the partial pressure of carbon dioxide (P_aCO₂) levels in patients with acute hypercapnic respiratory failure (AHRF).

MATERIAL AND METHODS: This retrospective observational study included patients treated in the emergency department (ED) with respiratory distress and P_aCO₂ > 45 mmHg. Patients were divided into two groups (DCPAP and non-DCPAP), depending on the treatment received to treat AHRF. The difference between the baseline P_aCO₂ levels in the first blood gas obtained from patients at the time of admission and the follow-up blood gas after treatment. Then, the calculated P_aCO₂ decrease was divided by the time elapsed to obtain the rate of decrease in PaCO₂ levels in mmHg/min. The statistical analyses were performed using SPSS version 18.0 software. A p value of < 0.05 was considered statistically significant.

RESULTS: A total of 61 patients were included in the study, 31 patients in the DCPAP group and 30 patients in the non-DCPAP group. The mean age of the patients was 74.03 ± 10.04, and the male/female was 23/38. The study demonstrated a statistically significant difference between the DCPAP and non-DCPAP groups in terms of P_aCO₂ decreasing rate, and it was found to be twice higher in the DCPAP group (0.11 ± 0.07 mmHg/min) than in the non-DCPAP group (0.05 ± 0.06 mmHg/min).

CONCLUSION: The study demonstrated that the treatment of AHRF patients with a DCPAP provides a faster decrease in P_aCO₂ levels in hypercapnic patients compared to standard medical therapy alone.

PMID:36243821 | DOI:10.1007/s11845-022-03189-2

Abdom Radiol (NY). 2022 Oct 15. doi: 10.1007/s00261-022-03702-2. Online ahead of print.

ABSTRACT

PURPOSE: To describe ultrasound (US) quality for hepatocellular carcinoma (HCC) screening/surveillance using the US LI-RADS scoring system, and to assess predictive factors of worse US quality scores.

METHODS: This retrospective study included adult patients (n = 470; M/F 264/206, median age 59y) at risk for HCC that underwent US for HCC screening/surveillance. US examinations were independently reviewed by 2 radiologists that assigned a visualization score (A: no/minimal, B: moderate, C: severe limitation) and US diagnostic category (US LI-RADS 1: negative, US LI-RADS 2: subthreshold, US LI-RADS 3: positive) to each study. A generalized linear mixed model was used to assess the predictive factors of worse visualization score using OR (odds ratio) statistics. Simple Kappa coefficient (K) assessed inter-reader agreement.

RESULTS: For readers 1 and 2, 295/320 (62.8%/68.1%) cases were scored A, 153/134 (32.6%/28.5%) were scored B, and 22/16 (4.6%/3.4%) were scored C, respectively. There was moderate inter-reader agreement for US LI-RADS visualization score (K = 0.478) and 100% concordance for US diagnostic category (K = 1), with 30 (6.4%) cases scored as positive (US LI-RADS 3). Cirrhosis and obesity were significant independent predictors of worse visualization scores (B/C) (cirrhosis: OR 10.4 confidence intervals: [4.25-25.48], p < 0.001; obesity: OR 3.61 [2.11-6.20], p < 0.001). Of the 30 lesions scored as US LI-RADS 3, 9 were characterized as probable or definite HCC on confirmatory CT/MRI, yielding a PPV of 30% (9/30) and a false-positive rate of 70% (21/30).

CONCLUSION: Moderate to severe limitations in quality of US performed for HCC screening/surveillance was observed in approximately one-third of patients. Patients with cirrhosis and/or elevated BMI have poorer quality US studies and may benefit from other screening modalities such as CT or MRI.

PMID:36243829 | DOI:10.1007/s00261-022-03702-2

Sci Rep. 2022 Oct 15;12(1):17323. doi: 10.1038/s41598-022-22335-5.

ABSTRACT

The potential of the surface dielectric barrier discharge technique (SDBD) was evaluated to decontaminate the date palm fruit. Preliminary investigations emphasized that Aspergillus niger fungus was predominant in most date samples as a post-harvest infestation. The influence of SDBD techniques on the viability of A. niger isolated from date varieties was investigated and documented. Physical and chemical characterizations of treated dates were assessed, and statistical correlation coefficients were calculated and elucidated. A 4 log₁₀ reduction of A. niger radial growth was observed at 3 min exposure/15 days of incubation. Simultaneous reductions in pH, water activity, and moisture content of treated dates were observed when compared to untreated dates. Statistical analysis showed a positive correlation between physical and chemical variables with the viability of A. niger in treated samples. Therefore, we believe that SDBD treatment will be a promising technique for decontaminating date fruits from attacked fungi, which will positively impact sustainable food security and consumer health.

PMID:36243776 | DOI:10.1038/s41598-022-22335-5

Sci Data. 2022 Oct 15;9(1):626. doi: 10.1038/s41597-022-01736-1.

ABSTRACT

The holistic nature of omics studies makes them ideally suited to generate hypotheses on health and disease. Sequencing-based genomics and mass spectrometry (MS)-based proteomics are linked through epigenetic regulation mechanisms. However, epigenomics is currently mainly focused on DNA methylation status using sequencing technologies, while studying histone posttranslational modifications (hPTMs) using MS is lagging, partly because reuse of raw data is impractical. Yet, targeting hPTMs using epidrugs is an established promising research avenue in cancer treatment. Therefore, we here present the most comprehensive MS-based preprocessed hPTM atlas to date, including 21 T-cell acute lymphoblastic leukemia (T-ALL) cell lines. We present the data in an intuitive and browsable single licensed Progenesis QIP project and provide all essential quality metrics, allowing users to assess the quality of the data, edit individual peptides, try novel annotation algorithms and export both peptide and protein data for downstream analyses, exemplified by the PeptidoformViz tool. This data resource sets the stage for generalizing MS-based histone analysis and provides the first reusable histone dataset for epidrug development.

PMID:36243775 | DOI:10.1038/s41597-022-01736-1