Category: Statistics

BMC Pharmacol Toxicol. 2025 Jan 13;26(1):6. doi: 10.1186/s40360-024-00831-w.

ABSTRACT

Hepatic encephalopathy (HE) is a syndrome that arises from acute or chronic liver failure. This study was devised to assess the impact of a combination of boswellic acid (BA) and low doses of gamma radiation (LDR) on thioacetamide (TAA)-induced HE in an animal model. The effect of daily BA treatment (175 mg/kg body weight, for four weeks) and/or fractionated low-dose γ-radiation (LDR; 0.25 Gy, twice the total dose of 0.5 Gy) was evaluated against TAA (200 mg/kg, intraperitoneal) twice-weekly for four weeks to induce liver damage and HE in rats. TAA-exposed rats exhibited a significant elevation in serum activities of liver enzymes (GGT, ALP) and plasma ammonia levels at P < 0.05 (Duncan’s test) compared to the control group. Moreover, there was an increase in the levels of proinflammatory cytokines (IL6, IL12, IL18) in the TAA-exposed animals accompanied by a depletion in the activities of paraoxonase-1 and neurotransmitter contents compared with normal control rats (P < 0.05). However, the administration of BA alone or in combination with LDR led to improvements in liver and brain parameter indices. Furthermore, the histopathological assessments of liver and brain tissues supported the findings of the biochemical investigations. From the statistical analysis, it can be concluded that the combined administration of BA and exposure to LDR may possess potential hepatoprotective effects against hepatic encephalopathy-associated hyperammonemia and the consequent damage to the liver and brain. This study proposes that a combination of therapeutic approaches, LDR and BA could be a new therapeutic candidate for the management of hepatic encephalopathy.

PMID:39806460 | DOI:10.1186/s40360-024-00831-w

Health Res Policy Syst. 2025 Jan 13;23(1):8. doi: 10.1186/s12961-024-01271-y.

ABSTRACT

During public health crises such as pandemics, governments must rapidly adopt and implement wide-reaching policies and programs (“public policy interventions”). A key takeaway from the coronavirus disease 2019 (COVID-19) pandemic was that although numerous randomized controlled trials (RCTs) focussed on drugs and vaccines, few policy experiments were conducted to evaluate effects of public policy interventions across various sectors on viral transmission and other consequences. Moreover, many quasi-experimental studies were of spurious quality, thus proving unhelpful for informing public policy. The pandemic highlighted the need to continuously develop competence, capacity and a robust legal-ethical foundation for impact evaluations well before crises occur. It raised a crucial question: how can governments in non-crisis times develop capabilities to generate evidence on the effects of public policy interventions, thus enabling a rapid and effective research response during public health crises? We conducted a mapping to explore how government agencies in Norway use RCTs and quasi-experimental methods to strengthen the evidence base for public policy interventions and to identify barriers and facilitators to their use. Contributing to the study were 10 government agencies across sectors such as development assistance, education, health, social welfare, statistics and taxation. Many of these agencies have conducted or commissioned RCTs or quasi-experimental studies in the past 5 years, with evaluations ranging from 1 or 2 to more than 15 per agency. The measures evaluated included organizational, educational and financial interventions and interventions for oversight and sanctions. Some agencies have internal capabilities for designing and conducting evaluations, while others commissioned such studies to universities and other research institutions. Agencies reported examples where enhanced communication among implementers, researchers, ministries and political leaders facilitated impact evaluations, and these lessons offer opportunities for cross-sector knowledge-sharing to help strengthen rigorous evaluations of public policy interventions. Despite their potential, various government agencies report that randomized and quasi-experimental studies face legal, ethical, political and practical barriers that affect their use. For instance, the urgency of politicians to implement policies at scale has led to the discontinuation of trials and hindered learning from their effects. The surveyed agencies stressed the importance of legislation providing clear guidelines on when differential treatment can be justified and when informed consent requirements can be waived, as well as faster and clearer processes for managing privacy concerns related to data access. Crucially, greater political acceptance for systematically and gradually implementing reforms, including using randomization, could strengthen evidence-informed public policy, enhancing the scaling-up of effective interventions and deprioritizing ineffective ones.

PMID:39806454 | DOI:10.1186/s12961-024-01271-y

J Cheminform. 2025 Jan 13;17(1):4. doi: 10.1186/s13321-025-00946-0.

ABSTRACT

Current strategies centred on either merging or linking initial hits from fragment-based drug design (FBDD) crystallographic screens generally do not fully leaverage 3D structural information. We show that an algorithmic approach (Fragmenstein) that ‘stitches’ the ligand atoms from this structural information together can provide more accurate and reliable predictions for protein-ligand complex conformation than general methods such as pharmacophore-constrained docking. This approach works under the assumption of conserved binding: when a larger molecule is designed containing the initial fragment hit, the common substructure between the two will adopt the same binding mode. Fragmenstein either takes the atomic coordinates of ligands from a experimental fragment screen and combines the atoms together to produce a novel merged virtual compound, or uses them to predict the bound complex for a provided molecule. The molecule is then energy minimised under strong constraints to obtain a structurally plausible conformer. The code is available at https://github.com/oxpig/Fragmenstein .Scientific contributionThis work shows the importance of using the coordinates of known binders when predicting the conformation of derivative molecules through a retrospective analysis of the COVID Moonshot data. This method has had a prior real-world application in hit-to-lead screening, yielding a sub-micromolar merger from parent hits in a single round. It is therefore likely to further benefit future drug design campaigns and be integrated in future pipelines.

PMID:39806443 | DOI:10.1186/s13321-025-00946-0

Respir Res. 2025 Jan 13;26(1):16. doi: 10.1186/s12931-024-03086-5.

ABSTRACT

BACKGROUND: The emergence of new molecular targeted drugs marks a breakthrough in asthma treatment, particularly for severe cases. Yet, options for moderate-to-severe asthma treatment remain limited, highlighting the urgent need for novel therapeutic drug targets. In this study, we aimed to identify new treatment targets for asthma using the Mendelian randomization method and large-scale genome-wide association data (GWAS).

METHODS: We utilized GWAS data from the UK Biobank (comprising 56,167 patients and 352,255 control subjects) and the FinnGen cohort (including 23,834 patients and 228,085 control subjects). Genetic instruments for 734 plasma proteins and 154 cerebrospinal fluid proteins were derived from recently published GWAS. Bidirectional Mendelian randomization analysis, Steiger filtering, colocalization, and phenotype scanning were employed for reverse causal inference detection, further substantiating the Mendelian randomization results. A protein-protein interaction network was also constructed to reveal potential associations between proteins and asthma medications.

RESULTS: Under Bonferroni significance conditions, Mendelian randomization analysis revealed causal relationships between seven proteins and asthma. In plasma, we observed that an increase of one standard deviation in IL1R1[1.30 (95% CI 1.20-1.42)], IL7R[1.07 (95% CI 1.04-1.11)], ECM1[1.03 (95% CI 1.02-1.05)], and CD200R1[1.18 (95% CI 1.09-1.27)] were associated with an increased risk of asthma, while an increase in ADAM19 [0.87 (95% CI 0.82-0.92)] was found to be protective. In the brain, each 10-fold increase in IL-6 sRa [1.29 (95% CI 1.15-1.45)] was associated with an increased risk of asthma, while an increase in Layilin [0.61 (95% CI 0.51-0.73)] was found to be protective. None of the seven proteins exhibited a reverse causal relationship. Colocalization analysis indicated that ECM1 (coloc.abf-PPH4 = 0.953), IL-6 sRa (coloc.abf-PPH4 = 0.966), and layilin (coloc.abf-PPH4 = 0.975) shared the same genetic variation as in asthma.

CONCLUSION: A causal relationship exists between genetically determined protein levels of IL1R1, IL7R, ECM1, CD200R1, ADAM19, IL-6 sRa, and Layilin (LAYN) and asthma. Moreover, the identified proteins may serve as attractive drug targets for asthma, especially ECM1 and Layilin (LAYN). However, further research is required to comprehensively understand the roles of these proteins in the occurrence and progression of asthma.

PMID:39806440 | DOI:10.1186/s12931-024-03086-5

Orphanet J Rare Dis. 2025 Jan 13;20(1):21. doi: 10.1186/s13023-024-03484-4.

ABSTRACT

BACKGROUND: Intestinal Behçet’s syndrome (IBS) has high morbidity and mortality rates with serious complications. However, there are few specific biomarkers for IBS. The purposes of this study were to investigate the distinctive metabolic changes in plasma samples between IBS patients and healthy people, active IBS and inactive IBS patients, and to identify candidate metabolic biomarkers which would be useful for diagnosing and predicting IBS.

METHODS: In this study, we performed a global untargeted metabolomics approach in plasma samples from 30 IBS patients and 20 healthy subjects. P value < 0.05 and variable importance projection (VIP) values > 1 were considered to be statistically significant metabolites. Univariate receiver operating characteristic (ROC) curve analysis was plotted as a measure for assessing the clinical performance of metabolites, and area under curve (AUC) were assessed.

RESULTS: A total of 147 differentially abundant metabolites (DAMs) were identified between IBS patients and normal control (NC) group. The potential pathways involved in the pathogenesis of IBS include linoleic acid metabolism; GABAergic synapse; biosynthesis of unsaturated fatty acids; valine, leucine and isoleucine biosynthesis; ovarian steroidogenesis; and others. In addition, a total of 103 significant metabolites were selected to distinguish active IBS from inactive IBS patients. Tyrosine metabolism, dopaminergic synapse and neuroactive ligand-receptor interaction were found to be closely related to the disease activity of IBS. Furthermore, three potential metabolites including quinate, stearidonic acid (SDA) and capric acid (CA) could significantly differ IBS patients from NC group. On the other hand, 1-methyladenosine (m1A), genipin, methylmalonic acid (MMA) and ascorbate could significantly differentiated active IBS from inactive IBS patients.

CONCLUSION: In conclusion, this study demonstrated the characteristic plasma metabolic profiles between IBS group and NC group, as well as between active and inactive IBS patients by using an untargeted LC/MS metabolomics profiling approach. In this study, quinate, SDA and CA were identified as potential diagnostic biomarkers for IBS. Additionally, m1A, genipin, MMA and ascorbate could serve as potential biomarkers for evaluating IBS activity. These findings might provide potential valuable insights for developing therapeutic strategies to manage IBS in the future.

PMID:39806438 | DOI:10.1186/s13023-024-03484-4

Mol Autism. 2025 Jan 13;16(1):2. doi: 10.1186/s13229-025-00639-3.

ABSTRACT

BACKGROUND: Alterations in sensory perception, a core phenotype of autism, are attributed to imbalanced integration of sensory information and prior knowledge during perceptual statistical (Bayesian) inference. This hypothesis has gained momentum in recent years, partly because it can be implemented both at the computational level, as in Bayesian perception, and at the level of canonical neural microcircuitry, as in predictive coding. However, empirical investigations have yielded conflicting results with evidence remaining limited. Critically, previous studies did not assess the independent contributions of priors and sensory uncertainty to the inference.

METHOD: We addressed this gap by quantitatively assessing both the independent and interdependent contributions of priors and sensory uncertainty to perceptual decision-making in autistic and non-autistic individuals (N = 126) during an orientation categorization task.

RESULTS: Contrary to common views, autistic individuals integrated the two Bayesian components into their decision behavior, and did so indistinguishably from non-autistic individuals. Both groups adjusted their decision criteria in a suboptimal manner.

LIMITATIONS: This study focuses on explicit priors in a perceptual categorization task and high-functioning adults. Thus, although the findings provide strong evidence against a general and basic alteration in prior integration in autism, they cannot rule out more specific cases of reduced prior effect – such as due to implicit prior learning, particular level of decision making (e.g., social), and level of functioning of the autistic person.

CONCLUSIONS: These results reveal intact inference for autistic individuals during perceptual decision-making, challenging the notion that Bayesian computations are fundamentally altered in autism.

PMID:39806435 | DOI:10.1186/s13229-025-00639-3

BMC Health Serv Res. 2025 Jan 13;25(1):66. doi: 10.1186/s12913-025-12214-w.

ABSTRACT

Health service policies are evolving into qualified health care providing best possible outcomes as well as focused on patient satisfaction. Hence the qualification valued health care includes patient satisfaction measurements, it is suggested to get feedbacks during the assessment of outcomes from the patient’s perspective. Aging of the world population accelerates demand on rehabilitation medicine which means recovering impairments so is directly related with quality of life. This study measures the patient satisfaction among 286 patients referring to outpatient clinics and receiving therapy within Physical Medicine and Rehabilitation Unit of City Hospital in Balikesir, Turkey. Results showed 63.4 ± 2.6 years mean of age and female majority (63.6%). Region of therapy included 9.8% for total body, plegic syndromes, 19.6% for neck, 25.2% for shoulder, 21.6% for knee and 23.8% for lumbar regions. Patients are grouped in two according to ‘yes’ or ‘no’ answer of the question ‘Do you agree with you have benefit from applied treatment, does the treatment met your expectations?’. 274 patients (95.8%) were agree with therapy met their expectations. Article discusses one of the valid patient satisfaction questionnaire as evidence based outcome measures. In divisions the means of query scores were 3.9 for technical quality, 4.2 for communication with therapist, 3.6 for physical comfort, 3.9 for communication with secretary, 4.1 for communication with doctor, 3.5 for accessibility and 3.5 for cleanliness. Comparison of means among groups did not seem statistically significant as result of Mann-Whitney U test, p > 0.05. In conclusion in the context of qualified health service providing, it is essential to get feedback from health care receivers to measure satisfaction and this needs improvement of generally valid questionnairres. Improved communication and greater provider sensitivity towards patients can enhance patient satisfaction resulting as meeting the expectation.

PMID:39806434 | DOI:10.1186/s12913-025-12214-w

Cancer Treat Rev. 2025 Jan 6;133:102882. doi: 10.1016/j.ctrv.2025.102882. Online ahead of print.

ABSTRACT

BACKGROUND: Trastuzumab deruxtecan (T-DXd) has shown promising activity in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and central nervous system (CNS) involvement. In this updated meta-analysis, we explore the effectiveness of T-DXd in a large subset of patients with HER2-positive BC and CNS disease.

METHODS: A systematic search was made on September 16th, 2024, for studies investigating T-DXd in the scenario of HER2-positive BC and brain metastases (BMs) and/or leptomeningeal disease (LMD). We used random effects models for all statistical analyses.

RESULTS: We included 18 studies with 786 HER2-positive BC patients with CNS involvement (16 studies with 750 BMs patients and three studies with 36 LMD patients). We observed high overall antitumor responses (objective response rate [ORR], 60.4 %; disease control rate [DCR], 94.4 %; and clinical benefit rate [CBR], 79.3 %) and a 12-month PFS of 64.7 % and OS of 82.7 %. Intracranial ORR, DCR, and CBR were seen in 62.2 %, 88.6 %, and 68.6 % of patients, respectively, and 67.4 % achieved intracranial PFS at 12 months. Both stable and active BMs subgroups derived similar benefit from T-DXd. Better intracranial responses were seen for 33 patients with untreated BMs compared to 56 patients with previously treated or progressing lesions (odds ratio 3.82, 95 % confidence interval 1.3-10.8, p = 0.01). For the LMD group, T-DXd elicited intracranial ORR and CBR in 59.4 % and 94.1 % of patients, respectively.

CONCLUSIONS: This updated meta-analysis continues to support the overall and intracranial activity of T-DXd in patients with HER2-positive BC and CNS involvement, including those with LMD.

PMID:39805165 | DOI:10.1016/j.ctrv.2025.102882

Clin Neuropharmacol. 2025 Jan-Feb 01;48(1):7-12. doi: 10.1097/WNF.0000000000000620.

ABSTRACT

INTRODUCTION: Adjunctive therapies to treat OFF episodes resulting from long-term levodopa treatment in Parkinson disease (PD) are hampered by safety and tolerability issues. Istradefylline offers an alternative mechanism (adenosine A2A receptor antagonist) and therefore potentially improved tolerability.

METHODS: A systematic review of PD adjuncts published in 2011 was updated to include randomized controlled trials published from January 1, 2010-April 15, 2019. Pairwise meta-analyses were updated, and Bucher indirect comparisons were used to generate estimates of relative safety, presented as odds ratio (OR) and 95% confidence interval (CI) for comparators versus istradefylline.

RESULTS: Fifty-seven randomized controlled trials involving 11,517 patients were included in the meta-analysis. Relative to istradefylline, dopamine agonists and catechol-O-methyl transferase (COMT) inhibitors had statistically significant higher odds of dyskinesia and somnolence. Monoamine oxidase-B inhibitors had significantly higher odds of hypotension. Amantadine extended-release (ER) had statistically significant higher odds of hallucination, orthostatic hypotension, insomnia, and withdrawals due to adverse events. All interventions combined had significantly higher odds of dyskinesia versus istradefylline 20 mg and somnolence versus istradefylline 40 mg. Considering overall incidence of adverse events, COMT inhibitors and amantadine ER had statistically significant higher odds versus both istradefylline doses (COMT versus istradefylline 40 mg, OR: 1.33; 95% CI: 1.03, 1.75; versus istradefylline 20 mg, OR: 1.32; 95% CI: 1.01, 1.72; amantadine ER versus istradefylline 40 mg, OR: 3.45; 95% CI: 1.85, 6.25; versus istradefylline 20 mg, OR: 3.33; 95% CI: 1.82, 6.25).

CONCLUSION: Istradefylline was associated with a generally favorable safety profile relative to other adjunct medications in this study.

PMID:39805118 | DOI:10.1097/WNF.0000000000000620

J Neuroophthalmol. 2024 Nov 14. doi: 10.1097/WNO.0000000000002294. Online ahead of print.

ABSTRACT

BACKGROUND: Autosomal Dominant Optic Atrophy (ADOA) is a hereditary optic neuropathy characterized by retinal ganglion cell degeneration and optic nerve fiber loss. This study examined the correlation between clinical and structural parameters in patients with ADOA using optical coherence tomography (OCT) and explored potential clinical biomarkers.

METHODS: A cross-sectional, case-control observational study included 27 patients with ADOA and 27 age- and sex-matched healthy controls. Clinical examinations, OCT imaging, and OCT angiography (OCTA) were performed. Statistical analyses were conducted to establish correlations between clinical and OCT parameters.

RESULTS: Patients with ADOA exhibited gradual bilateral vision loss, central scotomas, and optic disc pallor. Structural OCT analysis revealed significant reductions in central macular thickness, macular volume, ganglion cell complex (GCC), and peripapillary retinal nerve fiber layer compared with controls. Correlation analysis demonstrated associations between worsening clinical parameters (best corrected visual acuity, Sloan Letters Low Contrast Chart 25%, Pseudoisochromatic Test) and increased OCT damage (structural and OCTA). GCC emerged, at least at exploratory terms, as the most important clinical biomarker in patients with ADOA given its multiple positive functional associations, while OCTA parameters correlated with visual field defects.

CONCLUSIONS: Our study revealed significant correlations between clinical and structural parameters in patients with ADOA, highlighting the importance of OCT in assessing disease severity. GCC measurement shows promise as a clinical biomarker, aiding in disease monitoring. OCTA parameters offer potential early biomarkers for vascular changes. These findings contribute to understanding ADOA pathophysiology and may improve patient diagnosis and management. Further research is warranted to validate these findings and explore potential therapeutic interventions.

PMID:39805076 | DOI:10.1097/WNO.0000000000002294