Category: Statistics

Metabolomics. 2024 Jan 5;20(1):13. doi: 10.1007/s11306-023-02081-z.

ABSTRACT

INTRODUCTION: The burden of stroke in patients with hypertension is very high, and its prediction is critical.

OBJECTIVES: We aimed to use plasma lipidomics profiling to identify lipid biomarkers for predicting incident stroke in patients with hypertension.

METHODS: This was a nested case-control study. Baseline plasma samples were collected from 30 hypertensive patients with newly developed stroke, 30 matched patients with hypertension, 30 matched patients at high risk of stroke, and 30 matched healthy controls. Lipidomics analysis was performed by ultrahigh-performance liquid chromatography-tandem mass spectrometry, and differential lipid metabolites were screened using multivariate and univariate statistical methods. Machine learning methods (least absolute shrinkage and selection operator, random forest) were used to identify candidate biomarkers for predicting stroke in patients with hypertension.

RESULTS: Co-expression network analysis revealed that the key molecular alterations of the lipid network in stroke implicate glycerophospholipid metabolism and choline metabolism. Six lipid metabolites were identified as candidate biomarkers by multivariate statistical and machine learning methods, namely phosphatidyl choline(40:3p)(rep), cholesteryl ester(20:5), monoglyceride(29:5), triglyceride(18:0p/18:1/18:1), triglyceride(18:1/18:2/21:0) and coenzyme(q9). The combination of these six lipid biomarkers exhibited good diagnostic and predictive ability, as it could indicate a risk of stroke at an early stage in patients with hypertension (area under the curve = 0.870; 95% confidence interval: 0.783-0.957).

CONCLUSIONS: We determined lipidomic signatures associated with future stroke development and identified new lipid biomarkers for predicting stroke in patients with hypertension. The biomarkers have translational potential and thus may serve as blood-based biomarkers for predicting hypertensive stroke.

PMID:38180633 | DOI:10.1007/s11306-023-02081-z

Int J Comput Assist Radiol Surg. 2024 Jan 5. doi: 10.1007/s11548-023-03044-4. Online ahead of print.

ABSTRACT

PURPOSE: Standardized uptake values (SUVs) derived from ¹⁸F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography are a crucial parameter for identifying tumors or abnormalities in an organ. Moreover, exploring ways to improve the identification of tumors or abnormalities using a statistical measurement tool is important in clinical research. Therefore, we developed a fully automatic method to create a personally normalized Z-score map of the liver SUV.

METHODS: The normalized Z-score map for each patient was created using the SUV mean and standard deviation estimated from blood-test-derived variables, such as alanine aminotransferase and aspartate aminotransferase, as well as other demographic information. This was performed using the least absolute shrinkage and selection operator (LASSO)-based estimation formula. We also used receiver operating characteristic (ROC) to analyze the results of people with and without hepatic tumors and compared them to the ROC curve of normal SUV.

RESULTS: A total of 7757 people were selected for this study. Of these, 7744 were healthy, while 13 had abnormalities. The area under the ROC curve results indicated that the anomaly detection approach (0.91) outperformed only the maximum SUV (0.89). To build the LASSO regression, sets of covariates, including sex, weight, body mass index, blood glucose level, triglyceride, total cholesterol, γ-glutamyl transpeptidase, total protein, creatinine, insulin, albumin, and cholinesterase, were used to determine the SUV mean, whereas weight was used to determine the SUV standard deviation.

CONCLUSION: The Z-score normalizes the mean and standard deviation. It is effective in ROC curve analysis and increases the clarity of the abnormality. This normalization is a key technique for effective measurement of maximum glucose consumption by tumors in the liver.

PMID:38180621 | DOI:10.1007/s11548-023-03044-4

Metabolomics. 2024 Jan 5;20(1):12. doi: 10.1007/s11306-023-02078-8.

ABSTRACT

INTRODUCTION: Alzheimer’s Disease (AD) is complex and novel approaches are urgently needed to aid in diagnosis. Blood is frequently used as a source for biomarkers; however, its complexity prevents proper detection. The analytical power of metabolomics, coupled with statistical tools, can assist in reducing this complexity.

OBJECTIVES: Thus, we sought to validate a previously proposed panel of metabolic blood-based biomarkers for AD and expand our understanding of the pathological mechanisms involved in AD that are reflected in the blood.

METHODS: In the validation cohort serum and plasma were collected from 25 AD patients and 25 healthy controls. Serum was analysed for metabolites using nuclear magnetic resonance (NMR) spectroscopy, while plasma was tested for markers of neuronal damage and AD hallmark proteins using single molecule array (SIMOA).

RESULTS: The diagnostic performance of the metabolite biomarker panel was confirmed using sparse-partial least squares discriminant analysis (sPLS-DA) with an area under the curve (AUC) of 0.73 (95% confidence interval: 0.59-0.87). Pyruvic acid and valine were consistently reduced in the discovery and validation cohorts. Pathway analysis of significantly altered metabolites in the validation set revealed that they are involved in branched-chain amino acids (BCAAs) and energy metabolism (glycolysis and gluconeogenesis). Additionally, strong positive correlations were observed for valine and isoleucine between cerebrospinal fluid p-tau and t-tau.

CONCLUSIONS: Our proposed panel of metabolites was successfully validated using a combined approach of NMR and sPLS-DA. It was discovered that cognitive-impairment-related metabolites belong to BCAAs and are involved in energy metabolism.

PMID:38180611 | DOI:10.1007/s11306-023-02078-8

Eur Arch Otorhinolaryngol. 2024 Jan 5. doi: 10.1007/s00405-023-08432-9. Online ahead of print.

ABSTRACT

PURPOSE: Treatment de-intensification for p16 + oropharyngeal squamous cell carcinoma (OPSCC) is an area of active research to reduce the side effects and improve patients’ quality of life (QoL). In this paper we evaluated the Overall Survival (OS), the Disease-Free Survival (DFS) and the QoL of patients affected by p16 + OPSCC according to their prognostic stage group (PSG) and different treatments.

METHODS: Patients were selected retrospectively through our Electronic Tumor Board Database according to prespecified inclusion criteria. Basic data of eligible patients were recorded and analyzed. Then, OS and DFS were evaluated according to the PSG and the treatments performed. Patients alive completed three questionnaires: the QoL Questionnaire Core 30 (QLQ-C30), the QoL Questionnaire Head & Neck 43 (QLQ-HN43) and the MD Anderson Dysphagia Inventory (MDADI) questionnaire.

RESULTS: Sixty-one patients were included in this study. Eight patients died from the disease and the remaining 53 patients completed the 3 questionnaires. Fifteen (25%) patients were treated with upfront surgery, 6 (10%) patients with definitive radiotherapy and 40 (65%) patients with concomitant chemoradiotherapy. Comparing the DFS and the OS of PSG I patients by the different treatments performed, no statistically significant difference was identified. Patients treated with upfront surgery showed better outcomes in some aspects of their QoL.

CONCLUSION: For p16 + OPSCC PSG I patients, upfront surgery can be considered a valid alternative to radiotherapy or chemoradiotherapy while maintaining a comparable DFS and OS and giving patients better results in terms of specific aspects of their QoL.

PMID:38180604 | DOI:10.1007/s00405-023-08432-9

Birth Defects Res. 2024 Jan 5. doi: 10.1002/bdr2.2295. Online ahead of print.

ABSTRACT

BACKGROUND: Orofacial clefts (OFCs) include cleft palate (CP), cleft lip (CL), and cleft lip with cleft palate (CLP) and require multidisciplinary healthcare services. Alberta, Canada has a publicly funded, universal access healthcare system. This study determined publicly funded healthcare costs for children with an OFC and compared these costs to children without congenital anomalies.

METHODS: This retrospective population-based cohort analysis used the Alberta Congenital Anomalies Surveillance System to identify children born between 2002 and 2018 with an isolated OFC. They were matched 1:1 to a reference cohort based on sex and year of birth. The study population included 1614 children, from birth to 17 years of age linked to administrative databases to estimate annual inpatient and outpatient costs. Average annual all-cause costs were compared using two-sample independent t tests.

RESULTS: The mean total cleft-related costs per patient were highest for children with CLP ($74,138 CAD, standard deviation (SD) $43,447 CAD), followed by CP ($53,062 CAD, SD $74,366 CAD), and CL ($35,288 CAD, SD $49,720 CAD). The mean total all-cause costs per child were statistically significantly higher (p < .001) in children with an OFC ($56,305 CAD, SD $57,744 CAD) compared to children without a congenital anomaly ($18,600 CAD, SD $61,300 CAD).

CONCLUSIONS: Despite public health strategies to mitigate risk factors, the trend for OFCs has remained stable in Alberta, Canada for over 20 years. The costs reported are useful to other jurisdictions for comparison, and to families, healthcare professionals, service planners, and policy makers.

PMID:38179866 | DOI:10.1002/bdr2.2295

J Magn Reson Imaging. 2024 Jan 5. doi: 10.1002/jmri.29217. Online ahead of print.

ABSTRACT

BACKGROUND: Changes in cerebral hemodynamics with aging are important for understanding age-related variation in neuronal health. While many prior studies have focused on gray matter, less is known regarding white matter due in part to measurement challenges related to the lower vascular density in white matter.

PURPOSE: To investigate the impact of age and sex on white matter hemodynamics in a Human Connectome Project in Aging (HCP-A) cohort using tract-based spatial statistics (TBSS).

STUDY TYPE: Retrospective cross-sectional.

POPULATION: Six hundred seventy-eight typically aging individuals (381 female), aged 36-100 years.

FIELD STRENGTH/SEQUENCE: Multi-delay pseudo-continuous arterial spin labeling (ASL) and diffusion-weighted pulsed-gradient spin-echo echo planar imaging sequences at 3.0 T.

ASSESSMENT: A skeleton of mean fractional anisotropy (FA) was produced using TBSS. This skeleton was used to project ASL-derived cerebral blood flow (CBF) and arterial transit time (ATT) measures onto white matter tracts.

STATISTICAL TESTS: General linear models were applied to white matter FA, CBF, and ATT maps, while covarying for age and sex. Threshold-free cluster enhancement multiple comparisons correction was performed for the effects of age and sex, thresholded at P_FWE < 0.05. CBF, ATT, and FA were compared between sex for each tract using analysis of covariance, with multiple comparisons correction for the number of tracts at P_FDR < 0.05.

RESULTS: Significantly lower white matter CBF and significantly prolonged white matter ATTs were associated with older age. These effects were widespread across tracts for ATT. Significant (P_FDR < 0.05) sex differences in ATT were observed across all tracts, and significant sex differences in CBF were observed in all tracts except the bilateral uncinate fasciculus. Females demonstrated significantly higher CBF compared to males across the lifespan. Few tracts demonstrated significant sex differences in FA.

DATA CONCLUSION: This study identified significant sex- and age-associated differences in white matter hemodynamics across tracts.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

PMID:38179863 | DOI:10.1002/jmri.29217

Circ Heart Fail. 2024 Jan 5:e010813. doi: 10.1161/CIRCHEARTFAILURE.123.010813. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolomics has become a valuable tool for identifying potential new biomarkers and metabolic profiles. It has the potential to improve the diagnosis and prognosis of different phenotypes of heart failure. To generate a distinctive metabolic profile, we assessed and compared the metabolic phenotypes of patients with acute decompensated heart failure (ADHF), patients with chronic heart failure (CHF), and healthy controls.

METHODS: Plasma metabolites were analyzed by liquid-chromatography mass spectrometry/mass spectrometry and the MxP Quant 500 kit in 15 patients with ADHF, 50 patients with CHF (25 with dilated cardiomyopathy, 25 with ischemic cardiomyopathy), and 13 controls.

RESULTS: Of all metabolites identified to be significantly altered, 3-indolepropionic acid and 1-methyl histidine showed the highest concentration differences in ADHF and CHF compared with control. Area under the curve-receiver operating characteristic analysis showed an area under the curve ≥0.8 for 3-indolepropionic acid and 1-methyl histidine, displaying good discrimination capabilities between control and patient cohorts. Additionally, symmetrical dimethylarginine (mean, 1.97±0.61 [SD]; P=0.01) was identified as a suitable biomarker candidate for ADHF and kynurenine (mean, 1.69±0.39 [SD]; P=0.009) for CHF when compared with control, both demonstrating an area under the curve ≥0.85.

CONCLUSIONS: Our study provides novel insights into the metabolic differences between ADHF and CHF and healthy controls. We here identify new metabolites for potential diagnostic and prognostic purposes.

PMID:38179791 | DOI:10.1161/CIRCHEARTFAILURE.123.010813

Front Biosci (Landmark Ed). 2023 Dec 28;28(12):358. doi: 10.31083/j.fbl2812358.

ABSTRACT

BACKGROUND: Systemic lupus erythematosus (SLE)-related hematological disorders have different pathogenic mechanisms involving immune dysregulation as well as microangiopathy. The current study aimed to assess the relationship between pro- and anti-inflammatory cytokines and SLE-related hematological abnormalities for Saudi Patients.

METHODS: The current cross-sectional study including 140 participants was performed at the Prince Mohammad bin Abdulaziz Hospital (PMAH), Riyadh, Saudi Arabia. Two blood samples were collected from each of the study participants for evaluation of the haematological indices including complete blood count (CBC), erythrocyte sedimentation rate (ESR), and cytokine profile (i.e., tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10)). Statistical analyses were performed using the Statistical Package of Social Sciences (SPSS) software, v25.

RESULTS: Haematological abnormalities were documented in 63% of SLE patients, and anaemia was the highest at 52%. Haemoglobin levels were found to be significantly lower among SLE patients compared to the controls (p < 0.001). In the cytokine profiles, the levels of TNF-α (p < 0.001), IL-6 (p < 0.001), and IL-10 (p = 0.009) were significantly higher among SLE patients compared to the controls. A positive correlation was also identified between TNF-α, platelet count, red cell distribution width (RDW), and ESR.

CONCLUSIONS: Haematological abnormalities were found to be the most common among SLE patients. Further, the correlation between cytokine profile and haematological indices indicates the influence of cytokines in the development of haematological abnormalities. Understanding hematological abnormalities and cytokines’ role in the pathogenesis of these abnormalities may aid in the early diagnosis and development of more specific SLE disease therapies.

PMID:38179775 | DOI:10.31083/j.fbl2812358

Front Biosci (Landmark Ed). 2023 Dec 29;28(12):366. doi: 10.31083/j.fbl2812366.

ABSTRACT

BACKGROUND: Humans are exposed to physical, biological, chemical, and psychological stressor throughout their life span. In recent years many medicinal plants have been shown to induce stress adapting and protective functions. Plant-derived extracts and vitamin E exhibit stress protection or resistance by normalizing cellular homeostasis and enhancing resistance to toxic stimuli to overcome cellular damage. Here we report the evaluation of a topical preparation (product test materials; PTM) containing an ingredient blend of Rhodiola Rosea, Eleutherococcus Senticosus (Siberian Ginseng), Rhaponticum Carthamoides, Inonotus Obliqus, and Slegainella Lepidophylla as the base formula and tested the addition of Lespedeza Capitata (leaf/stem) extract plus vitamin E and/or Aloe Vera to determine the induced protective functions in human skin when challenged with intrinsic and extrinsic stressors.

METHODS: The base topical preparation plus Lespedeza Capitata extract plus vitamin E or the base topical preparation plus vitamin E and Aloe Vera were assayed in vitro on (a) intrinsically stressed excised abdominoplasty skin, (b) full thickness (FT) skin equivalent models post-treated with a combination of ultra-violet (UV) B light (250 mJ/cm2) and diesel particular matter (DPM) (75 µg/mL) skin, for their effect on antioxidant, inflammation, and stress biomarker geners. Additionally, the bioadaptive activity of the PTMs was confirmed in providing resilience and protection against UV-induced erythema. For example, in a clinical study, daily topical application of the PTMs on the buttocks of 20 woman (18-78 years old), average age of 51.1 years, median body mass index (BMI) of 26.5 for 8 weeks followed by 2 minimal erythema dose (MED) of UVB exposure was accessed 24 hours after irradiation. Statistical analysis was performed by t-test and ANOVA, repectively.

RESULTS: Pretreatment with the topical PTMs on intrsinically stressed skin significantly reduced the expression of the stress gene biomarkers, p53, pro-inflammatory cytokines Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNFα) and the pro-apoptotic BCL2 associated X, apoptosis regulator (BAX) values compared to controls. Topical application of the PTMs on Full Thickness (FT) human skin treated with UVB light and DPM significantly enhanced the stress response by activating heat shock transcription factor 4 (HSF4) and heat shock protein family B (small) member 1 (HSPB1) gene levels belonging to the heat shock protein (HSP) family by significantly increasing the expression of heme oxygenase 1 (HMOX1). At the same time, significantly reducing IL-1β levels were observed plus protection of skin cells from toxicity ocurred by significantly increasing the expression of B-cell lymphoma 2 (BCL2) (anti-apoptotic gene). In the clinical study, daily topical applications of the PTMs for 8 weeks followed by 2MED of UVB irradiation with clinical assessment 24 hours later revealed a significantly reduced intensity of erythema when compared to the buttock region treated with UVB alone.

CONCLUSIONS: The PTMs containing adaptogen ingredients may confer stress resistance and induce stress protective responses against intrinsic as well as extrinsic stressors as demonstrated by the obtained in vitro and clinical evidence.

PMID:38179774 | DOI:10.31083/j.fbl2812366

Clin Exp Rheumatol. 2024 Jan 2. doi: 10.55563/clinexprheumatol/fq5d3i. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the serum level of soluble CD27 (sCD27) and its potential clinical significance in rheumatoid arthritis (RA).

METHODS: Serum sCD27 levels in RA patients, idiopathic inflammatory myopathy (IIM) patients, systemic lupus erythematosus (SLE) patients and healthy controls (HCs) were detected by enzyme-linked immunosorbent assay. The medical information and laboratory data of the patients were collected. Serum sCD27 levels in RA patients with different clinical features were analysed, as was the correlation between the clinical data and serum sCD27 levels. Independent samples t test, the Mann-Whitney U-test or Wilcoxon signed-rank test, and Spearman correlation were used for statistical analysis.

RESULTS: Levels of sCD27 were elevated in RA patients (3898 [2525, 5834] pg/mL) compared with IIM patients (2467 [1939, 3324] pg/mL) or HCs (1659 ± 648 pg/mL) (p 0.001). In addition, serum sCD27 levels correlated with age, erythrocyte sedimentation rate, C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A, immunoglobulin G, complement 4 and disease activity score in 28 joints in RA patients. Levels of sCD27 were higher in RF-positive RA patients (6054 ± 5842 pg/mL) than in RF-negative patients (3902 ± 2098 pg/mL), and a similar finding was also observed in anti-cyclic citrullinated peptide (anti-CCP) antibody-positive (5810 ± 5671 pg/mL) and anti-CCP-negative (4183 ± 2187 pg/mL) RA patients. Serum ESR, RF, IgA, IgG levels and DAS28-CRP were elevated in RA patients with higher sCD27 levels than in those with lower sCD27 levels (p<0.01).

CONCLUSIONS: Serum sCD27 might be a promising biomarker that reflects both disease activity and humoral immunity activity in RA.

PMID:38179730 | DOI:10.55563/clinexprheumatol/fq5d3i