Category: Statistics

Nat Commun. 2022 Aug 27;13(1):5062. doi: 10.1038/s41467-022-32477-9.

ABSTRACT

A major obstacle in diabetes is the metabolic or hyperglycemic memory, which lacks specific therapies. Here we show that glucose-mediated changes in gene expression largely persist in diabetic kidney disease (DKD) despite reversing hyperglycemia. The senescence-associated cyclin-dependent kinase inhibitor p21 (Cdkn1a) was the top hit among genes persistently induced by hyperglycemia and was associated with induction of the p53-p21 pathway. Persistent p21 induction was confirmed in various animal models, human samples and in vitro models. Tubular and urinary p21-levels were associated with DKD severity and remained elevated despite improved blood glucose levels in humans. Mechanistically, sustained tubular p21 expression in DKD is linked to demethylation of its promoter and reduced DNMT1 expression. Two disease resolving agents, protease activated protein C (3K3A-aPC) and parmodulin-2, reversed sustained tubular p21 expression, tubular senescence, and DKD. Thus, p21-dependent tubular senescence is a pathway contributing to the hyperglycemic memory, which can be therapeutically targeted.

PMID:36030260 | DOI:10.1038/s41467-022-32477-9

Sci Rep. 2022 Aug 27;12(1):14635. doi: 10.1038/s41598-022-18838-w.

ABSTRACT

The lack of invariance problem in speech perception refers to a fundamental problem of how listeners deal with differences of speech sounds produced by various speakers. The current study is the first to test the contributions of mentally stored distributional information in normalization of prosodic cues. This study starts out by modelling distributions of acoustic cues from a speech corpus. We proceeded to conduct three experiments using both naturally produced lexical tones with estimated distributions and manipulated lexical tones with f0 values generated from simulated distributions. State of the art statistical techniques have been used to examine the effects of distribution parameters in normalization and identification curves with respect to each parameter. Based on the significant effects of distribution parameters, we proposed a probabilistic parametric representation (PPR), integrating knowledge from previously established distributions of speakers with their indexical information. PPR is still accessed during speech perception even when contextual information is present. We also discussed the procedure of normalization of speech signals produced by unfamiliar talker with and without contexts and the access of long-term stored representations.

PMID:36030274 | DOI:10.1038/s41598-022-18838-w

Clin Epigenetics. 2022 Aug 27;14(1):107. doi: 10.1186/s13148-022-01323-6.

ABSTRACT

Nanopore sequencing has brought the technology to the next generation in the science of sequencing. This is achieved through research advancing on: pore efficiency, creating mechanisms to control DNA translocation, enhancing signal-to-noise ratio, and expanding to long-read ranges. Heterogeneity regarding epigenetics would be broad as mutations in the epigenome are sensitive to cause new challenges in cancer research. Epigenetic enzymes which catalyze DNA methylation and histone modification are dysregulated in cancer cells and cause numerous heterogeneous clones to evolve. Detection of this heterogeneity in these clones plays an indispensable role in the treatment of various cancer types. With single-cell profiling, the nanopore sequencing technology could provide a simple sequence at long reads and is expected to be used soon at the bedside or doctor’s office. Here, we review the advancements of nanopore sequencing and its use in the detection of epigenetic heterogeneity in cancer.

PMID:36030244 | DOI:10.1186/s13148-022-01323-6

BMC Neurosci. 2022 Aug 27;23(1):51. doi: 10.1186/s12868-022-00737-5.

ABSTRACT

BACKGROUND: Spinal cord injury (SCI) is a common trauma in clinical practices. Subacute SCI is mainly characterized by neuronal apoptosis, axonal demyelination, Wallerian degeneration, axonal remodeling, and glial scar formation. It has been discovered in recent years that inflammatory responses are particularly important in subacute SCI. However, the mechanisms mediating inflammation are not completely clear.

METHODS: The gene expression profiles of GSE20907, GSE45006, and GSE45550 were downloaded from the GEO database. The models of the three gene expression profiles were all for SCI to the thoracic segment of the rat. The differentially expressed genes (DEGs) and weighted correlation network analysis (WGCNA) were performed using R software, and functional enrichment analysis and protein-protein interaction (PPI) network were performed using Metascape. Module analysis was performed using Cytoscape. Finally, the relative mRNA expression level of central genes was verified by RT-PCR.

RESULTS: A total of 206 candidate genes were identified, including 164 up-regulated genes and 42 down-regulated genes. The PPI network was evaluated, and the candidate genes enrichment results were mainly related to the production of tumor necrosis factors and innate immune regulatory response. Twelve core genes were identified, including 10 up-regulated genes and 2 down-regulated genes. Finally, seven hub genes with statistical significance in both the RT-PCR results and expression matrix were identified, namely Itgb1, Ptprc, Cd63, Lgals3, Vav1, Shc1, and Casp4. They are all related to the activation process of microglia.

CONCLUSION: In this study, we identified the hub genes and signaling pathways involved in subacute SCI using bioinformatics methods, which may provide a molecular basis for the future treatment of SCI.

PMID:36030234 | DOI:10.1186/s12868-022-00737-5

Int J Equity Health. 2022 Aug 27;21(1):118. doi: 10.1186/s12939-022-01713-5.

ABSTRACT

BACKGROUND: Measuring health inequality is essential to ensure that everyone has equal accessibility to health care. Studies in the past have continuously presented and showed areas or groups of people affected by various inequality in accessing the health resources and services to help improve this matter. Alongside, disease prevention is as important to minimise the disease burden and improve health and quality of life. These aspects are interlinked and greatly contributes to one’s health.

METHOD: In this study, the Gini coefficient and Lorenz curve are used to give an indication of the overall health inequality. The impact of this inequality in granular level is demonstrated using Bayesian estimation for disease detection. The Bayesian estimation used a two-component modelling approach that separates the case detection process and incidence rate using a mixed Poisson distribution while capturing underlying spatio-temporal characteristics. Bayesian model averaging is used in conjunction with the two-component modelling approach to improve the accuracy of estimates by incorporating many candidate models into the analysis instead of using fixed component models. This method is applied to an infectious disease, influenza, in Victoria, Australia between 2013 and 2016 and the corresponding primary health care of the state.

RESULT: There is a relatively equal distribution of health resources and services pertaining to general practitioners (GP) and GP clinics in Victoria, Australia. Roughly 80 percent of the population shares 70 percent of the number of GPs and GP clinics. The Bayesian estimation with model averaging revealed that access difficulty to health services impacts both case detection probability and incidence rate. Minimal differences are recorded in the observed and estimated incidence of influenza cases considering social deprivation factors. In most years, areas in Victoria’s southwest and eastern parts have potential under-reported cases consistent with their relatively lower number of GP or GP clinics.

CONCLUSION: The Bayesian model estimated a slight discrepancy between the estimated incidence and the observed cases of influenza in Victoria, Australia in 2013-2016 period. This is consistent with the relatively equal health resources and services in the state. This finding is beneficial in determining areas with potential under-reported cases and under-served health care. The proposed approach in this study provides insight into the impact of health inequality in disease detection without requiring costly and time-extensive surveys and relying mainly on the data at hand. Furthermore, the application of Bayesian model averaging provided a flexible modelling framework that allows covariates to move between case detection and incidence models.

PMID:36030233 | DOI:10.1186/s12939-022-01713-5

Eur J Med Res. 2022 Aug 27;27(1):160. doi: 10.1186/s40001-022-00786-w.

ABSTRACT

BACKGROUND: How the hip dysplasia affects the spinopelvic alignment in developmental dysplasia of the hip (DDH) patients is unclear, but it is an essential part for the management of this disease. This study aimed to investigate the coronal and sagittal spinopelvic alignment and the correlations between the spinopelvic parameters and the extent of hip dysplasia or the low back pain in unilateral DDH patients.

METHODS: From September 2016 to March 2021, 22 unilateral patients were enrolled in the DDH group with an average age of 43.6 years and 20 recruited healthy volunteers were assigned to the control group with an average age of 41.4 years. The Cobb angle, seventh cervical vertebra plumbline-central sacral vertical line (C7PL-CSVL), third lumbar vertebra inclination angle (L3IA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK) and lumbar lordosis (LL) were measured on the standing anteroposterior and lateral full-length standing spine radiographs. Additionally, the Oswestry Disability Index (ODI) and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were used to assess the degree of low back pain.

RESULTS: Cobb angle (8.68 ± 6.21° vs. 2.31 ± 0.12°), L3IA (4.80 ± 5.47° vs. 0.83 ± 0.51°), C7PL-CSVL (1.65 ± 1.57 cm vs. 0.48 ± 0.33 cm), PT (15.02 ± 9.55° vs. 9.99 ± 2.97°) and TLK (7.69 ± 6.66° vs. 3.54 ± 1.63°) were significantly larger in DDH patients, whereas LL (37.41 ± 17.17° vs. 48.79 ± 7.75°) was significantly smaller (P < 0.05). No correlation was found between significantly different spinopelvic parameters and the extent of dysplasia. Statistical analysis revealed correlations between ODI and Cobb angle (r = 0.59, P < 0.01), PT (r = 0.49, P = 0.02), TK (r = -0.46, P = 0.03) and TLK (r = 0.44, P = 0.04). Correlations between JOABPQE score and the Cobb angle (r = -0.44, P = 0.04), L3IA (r = -0.53, P = 0.01), PT (r = -0.44, P = 0.04), and TK (r = 0.46, P = 0.03) were also observed.

CONCLUSIONS: Cobb angle, L3IA, C7PL-CSVL in coronal plane and PT, TLK in sagittal plane increased, while LL decreased in unilateral DDH patients. These significantly different spinopelvic parameters have no correlation with the extent of dysplasia. Changes in coronal and sagittal plane including Cobb angle, L3IA, PT, TK and TLK were associated with the low back pain in the patients with unilateral DDH.

PMID:36030216 | DOI:10.1186/s40001-022-00786-w

BMC Cancer. 2022 Aug 27;22(1):927. doi: 10.1186/s12885-022-10024-5.

ABSTRACT

BACKGROUND: Transthoracic single-port assisted laparoscopic five-step maneuver inferior mediastinal lymphadenectomy for Siewert type II adenocarcinoma of esophagogastric junction (AEG) has superiority in lower mediastinal lymph nodes dissection and digestive tract reconstruction. However, the right pleura was probably ruptured in this surgical technique. The aim of this study was to explore whether the infracardiac bursa (ICB) exposed could protect right pleura.

METHODS: We retrospectively collected and evaluated the clinical and pathological data of patients who underwent five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymphadenectomy for Siewert II AEG at Guangdong Provincial Hospital of Chinese Medicine between May 2017 and February 2022.

RESULTS: A total of 49 patients were eligible, including 31 patients in ICB exposed group (group A) and 18 patients in ICB unexposed group (group B). There were no statistically significant differences in baseline characteristics between the two groups. 4 patients (12.9%) had right pleura rupture in group A, while 14 patients (77.8%) in group B, and the difference was statistically significant (p < 0.001). Compared with group B, the extubation time of endotracheal intubation (10.0 (6.0 ~ 12.0) vs. 13.0 (8.0 ~ 15.0) min, p = 0.003) and thoracic drainage tube stay (6.0 (5.0 ~ 7.0) vs. 8.0 (6.0 ~ 10.5) days, p = 0.041) were significantly shorted in the group A. The drainage volume of thorax (351.61 ± 125.00 vs. 418.61 ± 207.86 mL, p = 0.146) was non-significant less and the rate of complications (3.2% vs. 11.1%, p = 0.074) was non-significant lower in group A compared with group B. The postoperative hospital stay (9.0 (8.0,13.0) vs. 9.0 (8.0,12.0) days, p = 0.983) were similar in two groups. No serious adverse event occurred in any patient.

CONCLUSIONS: The ICB exposed could protect the right pleura and may promote postoperative recovery, which may be used as an anatomical marker in inferior mediastinal lymphadenectomy.

PMID:36030215 | DOI:10.1186/s12885-022-10024-5

BMC Public Health. 2022 Aug 27;22(1):1625. doi: 10.1186/s12889-022-14042-7.

ABSTRACT

BACKGROUND: Identification of modifiable risk factors that may impact chronic disease risk is critical to public health. Our study objective was to conduct a theoretical population attributable risk analysis to estimate the burden of disease from low dairy intake and to estimate the impact of increased dairy intake on United States (US)-based disability adjusted life years (DALYs).

METHODS: We conducted a comprehensive literature review to identify statistically significant summary relative risk estimates (SRREs) from recent meta-analyses of dairy consumption and key chronic disease outcomes. The SRREs were applied to preventive fractions using a range of categories (low to high) for population consumption of dairy products. The preventive fraction estimates were then applied to the number of DALYs for each health outcome in the US based on 2019 WHO estimates. The population attributable risk proportion estimates were calculated using the inverse of the SRRE from each meta-analysis using the same range of categories of consumption. These values were subsequently applied to the DALYs estimates to estimate the theoretical burden of disease attributable to low dairy intake.

RESULTS: Statistically significant SRREs were identified in recent meta-analyses of total dairy consumption in relation to breast cancer, colorectal cancer, cardiovascular disease (CVD), type 2 diabetes (T2D), stroke, and hypertension. In this theoretical analysis, nearly 850,000 DALYs (or 5.0% of estimated years of healthy life lost) due to CVD and 200,000 DALYs (4.5%) due to T2D may be prevented by increased dairy consumption. Approximately 100,000 DALYs due to breast cancer (7.5%) and approximately 120,000 DALYs (8.5%) due to colorectal cancer may be prevented by high dairy intake. The numbers of DALYs for stroke and hypertension that may be prevented by increased dairy consumption were approximately 210,000 (6.0%) and 74,000 (5.5%), respectively.

CONCLUSIONS: Consumption of dairy products has been associated with decreased risk of multiple chronic diseases of significant public health importance. The burden of disease that may potentially be prevented by increasing dairy consumption is substantial, and population-wide improvement in meeting recommended daily dairy intake goals could have a notable public health impact. However, this analysis is theoretical, and thus additional studies providing empirical evidence are needed to further clarify potential relationships between dairy intake and various health outcomes.

PMID:36030208 | DOI:10.1186/s12889-022-14042-7

Cardiovasc Diabetol. 2022 Aug 27;21(1):166. doi: 10.1186/s12933-022-01603-8.

ABSTRACT

BACKGROUND: Among individuals with atherosclerotic cardiovascular disease (ASCVD), type 2 diabetes mellitus (T2DM) is common and confers increased risk for morbidity and mortality. Differentiating risk is key to optimize efficiency of treatment selection. Our objective was to develop and validate a model to predict risk of major adverse cardiovascular events (MACE) comprising the first event of cardiovascular death, myocardial infarction (MI), or stroke for individuals with both T2DM and ASCVD.

METHODS: Using data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), we used Cox proportional hazards models to predict MACE among participants with T2DM and ASCVD. All baseline covariates collected in the trial were considered for inclusion, although some were excluded immediately because of large missingness or collinearity. A full model was developed using stepwise selection in each of 25 imputed datasets, and comprised candidate variables selected in 20 of the 25 datasets. A parsimonious model with a maximum of 10 degrees of freedom was created using Cox models with least absolute shrinkage and selection operator (LASSO), where the adjusted R-square was used as criterion for selection. The model was then externally validated among a cohort of participants with similar criteria in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial. Discrimination of both models was assessed using Harrell’s C-index and model calibration by the Greenwood-Nam-D’Agostino statistic based on 4-year event rates.

RESULTS: Overall, 1491 (10.2%) of 14,671 participants in TECOS and 130 (9.3%) in the ACCORD validation cohort (n = 1404) had MACE over 3 years’ median follow-up. The final model included 9 characteristics (prior stroke, age, chronic kidney disease, prior MI, sex, heart failure, insulin use, atrial fibrillation, and microvascular complications). The model had moderate discrimination in both the internal and external validation samples (C-index = 0.65 and 0.61, respectively). The model was well calibrated across the risk spectrum-from a cumulative MACE rate of 6% at 4 years in the lowest risk quintile to 26% in the highest risk quintile.

CONCLUSION: Among patients with T2DM and prevalent ASCVD, this 9-factor risk model can quantify the risk of future ASCVD complications and inform decision making for treatments and intensity.

PMID:36030198 | DOI:10.1186/s12933-022-01603-8

J Cosmet Dermatol. 2022 Aug 27. doi: 10.1111/jocd.15335. Online ahead of print.

ABSTRACT

BACKGROUND: Ligularia fischeri is a perennial herb isolated from plants of the Asteraceae family. Ligularia fischeri is distributed throughout Korea, Japan, eastern Siberia, and China.

AIMS: To examine the intracellular inhibitory effect of Ligularia fischeri ethanol extract on melanin synthesis and expression of tyrosinase and tyrosinase-related protein 1 and 2. In addition, we analyzed the mitogen-activated protein kinase signaling pathway and microphthalmia-associated transcription factor in alpha-melanocyte-stimulating hormone-stimulated B16F10 melanoma cells.

METHODS: To assess the inhibition of melanogenesis in alpha-melanocyte-stimulating hormone-stimulated B16F10 melanoma cells, the expression of melanogenesis-related genes was investigated by quantitative real-time polymerase chain reaction, while western blotting was performed to determine protein expression levels.

RESULTS: We confirmed that the ethanol extract of Ligularia fischeri inhibited melanin synthesis in vitro by decreasing tyrosinase and tyrosinase-related protein 1 and 2 expression. Furthermore, we revealed that tyrosinase expression was regulated by the suppression of microphthalmia-associated transcription factor expression and activation of extracellular signal-regulated kinase phosphorylation. The ethanol extract of Ligularia fischeri inhibited melanogenesis by activating extracellular signal-regulated kinase phosphorylation and suppressing microphthalmia-associated transcription factor and tyrosinase expression.

CONCLUSIONS: Ligularia fischeri ethanol extract may be used as an effective skin whitening agent in functional cosmetics.

PMID:36030197 | DOI:10.1111/jocd.15335