Category: Statistics

Alzheimers Res Ther. 2025 Feb 7;17(1):39. doi: 10.1186/s13195-025-01688-9.

ABSTRACT

BACKGROUND: β-synuclein (β-syn), mainly expressed in central nerve system, is one of the biomarkers in cerebrospinal fluid (CSF) and blood for synaptic damage, which has been reported to be elevated in CSF and blood of the patients of prion diseases (PrDs).

METHODS: We analyzed 314 CSF samples from patients in China National Surveillance for CJD. The diagnostic groups of the 223 patients with PrDs included sporadic Creutzfeldt-Jacob disease (sCJD), genetic CJD (gCJD), fatal familial insomnia (FFI) and Gerstmann-Straussler-Scheinker (GSS). 91 patients with non-PrDs comprised Alzheimer’s disease (AD), Parkinson’s disease (PD), viral encephalitis (VE) or autoimmune encephalitis (AE) were enrolled in the control groups. The CSF β-syn levels were measured by a commercial microfluidic ELISA. The Mann-Whitney U test and Kruskal-Wallis H test were employed to analyze two or more sets of continuous variables. Multiple linear regression was also performed to evaluate the factors for CSF β-syn levels. Receiver operating characteristics (ROC) curves and area under the curve (AUC) values were used to assess the diagnostic performance of β-syn.

RESULTS: The median of β-syn levels (2074 pg/ml; IQR: 691 to 4332) of all PrDs was significantly higher than that of non-PrDs group (504 pg/ml; IQR: 126 to 3374). The CSF β-syn values in the cohorts of sCJD, T188K-gCJD, E200K-gCJD and P102L-GSS were remarkably higher than that of the group of AD + PD, but similar as that of the group of VE + AE. The elevated CSF β-syn in sCJD and gCJD cases was statistically associated with CSF 14-3-3 positive and appearance of mutism. ROC curve analysis identified satisfied performance for distinguishing from AD + PD, with high AUC values in sCJD (0.7640), T188K-gCJD (0.8489), E200K-gCJD (0.8548), P102L-GSS (0.7689) and D178N-FFI (0.7210), respectively.

CONCLUSION: Our data here indicate that CSF β-syn is a potential biomarker for distinguishing PrDs (gCJD, sCJD and GSS) from AD and PD, but is much less efficient from VE and AE. These findings have critical implications for early diagnosis and monitoring of synaptic integrity in prion diseases.

PMID:39920821 | DOI:10.1186/s13195-025-01688-9

Infect Agent Cancer. 2025 Feb 7;20(1):8. doi: 10.1186/s13027-025-00639-1.

ABSTRACT

BACKGROUND: Successful antiviral therapy significantly decreases the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Alpha-fetoprotein (AFP) in the serum is a valuable early indicator of HCC. However, it is unclear whether different antiviral medications have varying effects on AFP levels. The purpose of this study was to evaluate this issue in those treated with entecavir (ETV) versus tenofovir disoproxil fumarate (TDF).

METHODS: We prospectively enrolled treatment-naive CHB adults who commenced treatment with ETV or TDF. Their changes in biochemical, virological, and fibrosis parameters and the elevation of AFP or development of HCC during follow-up were analyzed.

RESULTS: A total of 1942 CHB patients were included (10-90% follow-up time 3-60 months), and 104 patients with elevated AFP (5.3%) and 27 patients with HCC development (1.4%) were identified during the follow-up. The difference in the cumulative incidence of AFP abnormalities and HCC was statistically significant between patients who received ETV or TDF therapy. Multivariate Cox regression showed that elevated liver stiffness with shear wave elastography (Hazard ratio (HR) = 1.05, 95% Confidence interval (CI) 1.03-1.08, P < 0.001) and abnormal AFP at baseline (HR = 1.00, 95% CI 1.00-1.00, P < 0.001) were independent risk factors for abnormal AFP in CHB patients, while shear wave elastography (HR = 1.07, 95% CI 1.02-1.12, P < 0.001) was also independent risk factor for HCC. Similar results were obtained after propensity score matching (PSM) analysis. The combination of shear wave elastography (SWE), mPage-B score, age and type 2 diabetes mellitus had an area under the curve of 0.838 (P < 0.001) in predicting the occurrence of HCC.

CONCLUSIONS: Similar AFP elevation and HCC development rates were observed in CHB patients treated with ETV or TDF. Elevated SWE and abnormal AFP at baseline were independent risk factors for abnormal AFP in CHB patients.

PMID:39920817 | DOI:10.1186/s13027-025-00639-1

J Neuroeng Rehabil. 2025 Feb 7;22(1):23. doi: 10.1186/s12984-025-01550-x.

ABSTRACT

BACKGROUND: Children with cerebral palsy (CP) often experience gait impairments. Robot-assisted gait training (RGT) has been shown to have beneficial effects in this patient population. However, clinical outcomes of RGT vary substantially from patient to patient. This study explored the hypothesis that clinical outcomes are associated with changes in muscle synergies in response to RGT.

METHODS: Thirteen children with CP and Gross Motor Function Classification Scale (GMFCS) levels I-IV were recruited in the study. Children participated in a 6 week-RGT intervention and underwent clinical evaluations and gait studies-with focus on the analysis of electromyographic (EMG) data-pre- and post-training. Lower-limb muscle synergies were derived from the EMG recordings. Pre- vs. post-RGT clinical outcomes and muscle synergies were compared to explore potential relationships.

RESULTS: Three and, less often, two muscle synergies were detected in study participants pre-RGT. Linear mixed effect models showed that composition of the muscle synergies and their temporal activation coefficients present deviations from normative data proportional to the severity of functional limitations (i.e., GMFCS levels, p < 0.01). At a group level, changes in muscle synergies pre- vs. post-RGT did not significantly correlate with changes in clinical outcomes (p > 0.05). However, it was observed that participants who displayed prominent changes in muscle synergies also displayed large improvements in clinical scores.

CONCLUSIONS: Gait impairments in children with CP were associated with muscle synergies that deviated from normative. Participants who demonstrated the most substantial improvements in clinical scores following RGT exhibited multiple changes in the muscle synergies. However, no statistically significant correlations were identified at the group level. Future studies relying on larger datasets are needed to further investigate this observation and potential underlying mechanisms.

PMID:39920813 | DOI:10.1186/s12984-025-01550-x

Transl Neurodegener. 2025 Feb 7;14(1):7. doi: 10.1186/s40035-025-00469-6.

ABSTRACT

BACKGROUND: Parkinson’s disease (PD) and multiple system atrophy (MSA) are two distinct α-synucleinopathies traditionally differentiated through clinical symptoms. Early diagnosis of MSA is problematic, and seed amplification assays (SAAs), such as real-time quaking-induced conversion (RT-QuIC), offer the potential to distinguish these diseases through their underlying α-synuclein (α-Syn) pathology and proteoforms. Currently, SAAs provide a binary result, signifying either the presence or absence of α-Syn seeds. To enhance the diagnostic potential and biological relevance of these assays, there is a pressing need to incorporate quantification and stratification of α-Syn proteoform-specific aggregation kinetics into current SAA pipelines.

METHODS: Optimal RT-QuIC assay conditions for α-Syn seeds extracted from PD and MSA patient brains were determined, and assay kinetics were assessed for α-Syn seeds from different pathologically relevant brain regions (medulla, substantia nigra, hippocampus, middle temporal gyrus, and cerebellum). The conformational profiles of disease- and region-specific α-Syn proteoforms were determined by subjecting the amplified reaction products to concentration-dependent proteolytic digestion with proteinase K.

RESULTS: Using our protocol, PD and MSA could be accurately delineated using proteoform-specific aggregation kinetics, including α-Syn aggregation rate, maximum relative fluorescence, the gradient of amplification, and core protofilament size. MSA cases yielded significantly higher values than PD cases across all four kinetic parameters in brain tissues, with the MSA-cerebellar phenotype having higher maximum relative fluorescence than the MSA-Parkinsonian phenotype. Statistical significance was maintained when the data were analysed regionally and when all regions were grouped.

CONCLUSIONS: Our RT-QuIC protocol and analysis pipeline can distinguish between PD and MSA, and between MSA phenotypes. MSA α-Syn seeds induce faster propagation and exhibit higher aggregation kinetics than PD α-Syn, mirroring the biological differences observed in brain tissue. With further validation of these quantitative parameters, we propose that SAAs could advance from a yes/no diagnostic to a theranostic biomarker that could be utilised in developing therapeutics.

PMID:39920796 | DOI:10.1186/s40035-025-00469-6

J Health Popul Nutr. 2025 Feb 7;44(1):29. doi: 10.1186/s41043-025-00749-x.

ABSTRACT

BACKGROUND: Health Workers Safety (HWS) is a global health priority and essential at all times, in stable situations, in emergencies, in disease epidemics or pandemics. This study aimed to assess HWS during the COVID-19 Pandemic.

METHODS: This cross-sectional study was conducted in 2022 in east Azerbaijan province, Iran. HWS was assessed based on 22 indicators suggested by WHO EMRO. We selected 15 PHC facilities and six wards from two hospitals randomly. Data collected (qualitative and quantitative) using national digital health records, staff records, and indicator-specific tools. In addition to measuring the indicator’s value, the indicators’ feasibility was also assessed. Descriptive and inferential statistics with SPSS-16 were used for data analysis.

RESULTS: Totally, 325 Health Workers (HWs) (218 from PHC facilities and 107 from hospitals) participated in the study. Most of the participants in PHC facilities and hospitals were Community Health Workers (CHWs) (Moragheb Salamat) (45.4%) and nurses (37.38%), respectively. Most of HWs had completed the full vaccination schedule for Hepatitis B and COVID-19. Personal Protective Equipment (PPE) safety protocols were adhered by most of HWs within a healthcare facility. None of managers had attended nationally certified training for mental health support for health and care workers. Less than 20% of HWs participated in the work burnout prevention courses and most of HWs complained about work overload, or burnout. The job satisfaction level of hospital HWs (60.20%) was significantly higher than that of HWs from PHC facilities (57.18%) (P < 0.001).

CONCLUSION: Even though the mental health of HWs was not as expected, the indicators related to physical health and occupational health were at a suitable level. Also, there is not a system in PHC to audit the application of safety measures to mitigate the risk of contracting COVID-19. We recommend creating a specific system (precise and detailed) for HWs’ safety and applying safety measures in the PHC routine programs.

PMID:39920792 | DOI:10.1186/s41043-025-00749-x

Diabetol Metab Syndr. 2025 Feb 7;17(1):47. doi: 10.1186/s13098-025-01612-z.

ABSTRACT

BACKGROUND: Research indicates that there may be an association between plasma lipidome levels and the incidence of diabetic retinopathy (DR) in patients. However, the potential causality of this relationship is yet to be determined. To investigate this matter further, we employed a two-sample Mendelian randomization (MR) analysis to comprehensively assess the causality between lipidome levels and DR.

METHODS: Summary statistics for lipid levels and DR were obtained from the Genome-Wide Association Studies (GWAS) Catalog database and the FinnGen Consortium, respectively. We conducted a two-sample MR analysis, and statistical analysis were performed using the inverse variance weighted (IVW) with the addition of the MR-Egger, weighted median (WM), constrained maximum likelihood and model averaging (cML-MA) to test for causal associations between lipid levels and DR. Heterogeneity was checked using Cochran’s Q statistic. The MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) global test and the MR-Egger regression were used to detect horizontal pleiotropy. The robustness of our findings was assessed using leave-one-out and funnel plots. To further assess the reliability of the results, linkage disequilibrium score regressions, colocalization analysis and reverse MR analysis were also performed.

RESULTS: Analysis of the pooled MR results and after correction for the false discovery rate (FDR) revealed that five lipid levels were associated with DR risk. Phosphatidylcholine (16:0_16:0) levels [OR = 0.869 (0.810 to 0.933), P_fdr = 0.006], phosphatidylcholine (16:0_20:2) levels [OR = 0.893 (0.834 to 0.956), P_fdr = 0.043] and phosphatidylethanolamine (18:0_20:4) levels [OR = 0.906 (0.863 to 0.951), P_fdr = 0.006] were protective against DR, whereas sphingomyelin (d36:1) levels [OR = 1.120 (1.061 to 1.183), P_fdr = 0.006], and sphingomyelin (d40:1) levels [OR = 1.081 (1.031 to 1.134), P_fdr = 0.043] were associated with a greater risk of DR. Further sensitivity analysis did not reveal heterogeneity or horizontal pleiotropy.

CONCLUSION: In summary, genetic evidence suggests a causal relationship between the levels of specific lipid levels and DR. These findings may provide valuable insights into the causal relationships between lipid levels and DR, potentially informing future prevention and treatment strategies.

PMID:39920782 | DOI:10.1186/s13098-025-01612-z

J Health Popul Nutr. 2025 Feb 7;44(1):31. doi: 10.1186/s41043-024-00712-2.

ABSTRACT

BACKGROUND: Diabetes mellitus, an endocrine system disease, is a common disease involving many patients worldwide. Many studies are performed to evaluate the correlation between micronutrients/macronutrients on diabetes but few of them have a high statistical population and a long follow-up period. We aimed to investigate the relationship between intake of macro/micronutrients and the incidence of type 2 diabetes (T2D) using logistic regression (LR) and a decision tree (DT) algorithm for machine learning.

METHOD: Our research explores supervised machine learning models to identify T2D patients using the Mashhad Cohort Study dataset. The study population comprised 9704 individuals aged 35-65 years were enrolled regarding their T2D status, and those with T2D history. 15% of individuals are diabetic and 85% of them are non-diabetic. For ten years (until 2020), the participants in the study were monitored to determine the incidence of T2D. LR is a statistical model applied in dichotomous response variable modeling. All data were analyzed by SPSS (Version 22) and SAS JMP software.

RESULT: Nutritional intake in the T2D group showed that potassium, calcium, magnesium, zinc, iodine, carotene, vitamin D, tryptophan, and vitamin B12 had an inverse correlation with the incidence of diabetes (p < 0.05). While phosphate, iron, and chloride had a positive relationship with the risk of T2D (p < 0.05). Also, the T2D group significantly had higher carbohydrate and protein intake (p-value < 0.05).

CONCLUSION: Machine learning models can identify T2D risk using questionnaires and blood samples. These have implications for electronic health records that can be explored further.

PMID:39920736 | DOI:10.1186/s41043-024-00712-2

BMC Musculoskelet Disord. 2025 Feb 7;26(1):134. doi: 10.1186/s12891-025-08384-7.

ABSTRACT

BACKGROUND: This meta-analysis aimed to determine whether resistance exercise training (RET) can attenuate the loss of muscle volume and function in anti-gravitational muscles, especially quadriceps and calf muscles, during immobilization/disuse conditions.

METHODS: A comprehensive literature search was conducted to identify randomized controlled trials comparing RET vs. no exercise during immobilization/disuse. Searches were conducted in databases including Web of Science, PubMed, EBOSCO, and Cochrane Library, without imposing a time limit until 20 March, 2023. Studies reporting outcomes related to muscle volume, MVC, peak power, concentric peak force, eccentric peak force, isometric MVC torque of knee extension, isometric MVC torque of knee flexion were included. Data were pooled using random-effects models.

RESULTS: Eleven randomized controlled trials were finally included. RET elicited substantial benefits for preserving quadriceps muscle volume (n = 5, MD = 252.56, 95% CI = 151.92, 353.21, p < 0.001). RET demonstrated a statistically significant preventive effect on the reduction of MVC in both quadriceps (n = 4, MD = 338.59, 95% CI = 247.49, 429.69, p < 0.001) and calf muscles (n = 3, MD = 478.59, 95% CI = 160.42, 796.77, p < 0.01). Peak power of quadriceps muscles (n = 4, MD = 166.08, 95% CI = 28.44, 303.73, p < 0.05) and calf muscles (n = 2, MD = 176.58, 95% CI = 102.36, 250.79, p < 0.001) were elevated after RET intervention. RET significantly ameliorated the weakening of both concentric and eccentric peak force in quadriceps (concentric: n = 2, MD = 470.95, 95% CI = 355.45, 586.44, p < 0.001; eccentric: n = 1, MD = 351.51, 95% CI = 254.43, 448.58, p < 0.001) and calf muscles (concentric: n = 2, MD = 867.52, 95% CI = 548.18, 1186.86, p < 0.001; eccentric: n = 1, MD = 899.86, 95% CI = 558.17, 1241.55, p < 0.001). Additionally, the diminishing of isometric MVC torques of knee extension (n = 6, MD = 41.85, 95% CI = 20.93, 62.77, p < 0.001) and knee flexion (n = 4, MD = 13.20, 95% CI = 8.12, 18.77, p < 0.001) were enhanced significantly after RET intervention.

CONCLUSIONS: RET effectively minimized deterioration of muscle volume and muscle function during immobilization/disuse, particularly in anti-gravitational muscles. RET should be recommended to maintain muscle and neuromuscular health for spaceflight, bed rest, immobilization/disuse conditions. Further research is needed to explore the effects of RET in more diverse populations and under various disuse conditions. More high-quality research will be required to demonstrate the aforementioned benefits conclusively.

PMID:39920735 | DOI:10.1186/s12891-025-08384-7

BMC Nurs. 2025 Feb 7;24(1):143. doi: 10.1186/s12912-025-02793-8.

ABSTRACT

AIM: This study carried out to examine the effects of nursing care given to coronary intensive care patients according to their circadian rhythms on sleep quality, pain, anxiety, and delirium.

STUDY DESIGN: This study was designed as a randomised controlled, clinical investigation. The study population consisted of patients treated in the coronary care unit of a training and research hospital between September 2022 and February 2023. Total of 44 participants were included. The included participants were followed up for 3 days in the coronary intensive care unit. Data were collected using “Patient Information Form, Sleep Quality Scale in Coronary Intensive Care Patients (SQ-CC), Visual Analogue Scale (VAS), Morningness-Eveningness Questionnaire (MEQ), Hospital Anxiety and Depression Scale (HADS), Intensive Care Delirium Screening Checklist (ICDSC).” In addition, melatonin and cortisol measurements were made, and sleep data were taken with a smartwatch. Patients with intermediate chronotype, delirium, on ventilator support, or using sedative drugs were excluded. The chronotypes of the participants were determined, and the patients in the intervention group were given nursing care by their circadian rhythms. No intervention was made to the control group, and their routine care was continued in accordance with intensive care unit functioning. Frequency distribution, dependent and independent sample t-test, Wilcoxon test, repeated measures analysis of variance, Mann Whitney U, and chi-square analysis were used to evaluate the data. The study has been registered in ClinicalTrials.gov (Identifiers: NCT04934436). During statistical analysis, the groups were coded as Group A and Group B, ensuring blinding for the statistician.

RESULTS: The intervention group’s sleep quality increased compared to the control group (post-test SQ-CC total scores: intervention group 22.41 ± 6.67 vs. control group 50.45 ± 10.63, p < 0.001). Although no significant difference was found between the groups as a result of the study, there was a significant decrease in the pain score in the intervention group (VAS pre-test: 1.55 ± 2.15, post-test: 0.68 ± 2.21, p = 0.036). The anxiety of the intervention group decreased significantly compared to the control group (post-test HADS-Anxiety scores: intervention group 3.18 ± 3.29 vs. control group 8.50 ± 5.66, p = 0.001). The post-test delirium score was higher in the control group compared to the intervention group (post-test ICDSC scores: intervention group 0.32 ± 0.48 vs. control group 1.18 ± 0.50, p < 0.001). Melatonin increased and cortisol decreased in both groups without statistically significant differences between them (melatonin and cortisol levels: p > 0.05). Considering the sound levels in the environment, the first-night decibel mean was significantly higher in the intervention group than in the control group (first-night decibel mean: intervention group 56.58 ± 2.43 dB vs. control group 54.51 ± 2.41 dB, p < 0.05). Finally, the smartwatch data show no significant difference in sleep times between groups (p < 0.05), but the intervention group had more deep and total sleep, while the control group had less deep sleep.

CONCLUSIONS: Nursing care given in accordance with the circadian rhythm increases sleep quality and reduces the risk of delirium and anxiety in patients followed up with acute coronary syndrome in the coronary intensive care unit.

PMID:39920733 | DOI:10.1186/s12912-025-02793-8

J Orthop Surg Res. 2025 Feb 7;20(1):147. doi: 10.1186/s13018-025-05545-1.

ABSTRACT

OBJECTIVE: Through this study we aimed to present the latest and most comprehensive pooled analysis, providing an updated evaluation of the efficacy and safety of sequential therapy for primary osteoporosis, using bone formation promoters followed by bone resorption inhibitors.

METHODS: PubMed, the Cochrane Library, Web of Science, and Embase databases were retrieved to identify pertinent studies. Randomized controlled trials (RCTs) on the sequential therapy of primary osteoporosis with bone formation promoters followed by bone resorption inhibitors were included. Data from clinical studies that met the eligibility criteria were extracted, and quality assessment and meta-analysis were performed using RevMan v5.4 and Stata v15.0. Sensitivity and subgroup analyses were performed to find the source of heterogeneity and discover more findings.

RESULTS: A total of 10 eligible articles involving 14,510 patients (7171 in the intervention group versus 7339 in the comparator group) were included for the evidence synthesis. The baseline characteristics of the two groups were similar. Pooled analysis showed that the intervention group (bone formation promoters followed by bone resorption inhibitors) increased BMD at the spine (SMD:1.64; 95% CI: 0.97, 2.31; P < 0.00001; I² = 99%), femoral neck (SMD: 0.57; 95% CI: 0.16, 0.99; P = 0.007; I² = 96%), and total hip (SMD: 0.82; 95% CI: 0.16, 1.48; P = 0.02; I² = 97%) compared with the comparator group (monotherapy or combination therapy using two drugs)for postmenopausal osteoporosis patient; however, there was no statistically significant difference observed in the increase of BMD at the 1/3 distal radius comparing the intervention group and comparator group (SMD: -0.25; 95% CI: -1.49, 0.99; P = 0.069; I² = 92%). The incidence of new fractures was reduced in the intervention group relative to the comparator group (RR: 0.60; 95% CI: 0.43, 0.82; P = 0.001; I² = 75%). The incidence of adverse events differed statistically between the two groups (RR: 0.85; 95% CI: 0.76, 0.95; P = 0.004; I² = 97%), but the difference in adverse event incidence was not statistically significant among subgroups within the intervention and comparator groups. The intervention group had a superiority of Clinical efficacy.

CONCLUSION: Among patients with primary osteoporosis, sequential therapy with bone formation promoters followed by bone resorption inhibitors substantially increased BMD at sites such as the spine, femoral neck, and total hip while concurrently mitigating fracture risks. However, benefits regarding BMD at the 1/3 distal radius and the incidence of adverse events have not yet been established.

STUDY REGISTRATION: Registered on PROSPERO (ID: CRD42023437188).

PMID:39920732 | DOI:10.1186/s13018-025-05545-1