Sci Rep. 2024 Mar 7;14(1):5655. doi: 10.1038/s41598-024-56270-4.
NO ABSTRACT
PMID:38454148 | DOI:10.1038/s41598-024-56270-4
Sci Rep. 2024 Mar 8;14(1):5693. doi: 10.1038/s41598-024-56208-w.
ABSTRACT
Identification of potential human-virus protein-protein interactions (PPIs) contributes to the understanding of the mechanisms of viral infection and to the development of antiviral drugs. Existing computational models often have more hyperparameters that need to be adjusted manually, which limits their computational efficiency and generalization ability. Based on this, this study proposes a kernel Bayesian logistic matrix decomposition model with automatic rank determination, VKBNMF, for the prediction of human-virus PPIs. VKBNMF introduces auxiliary information into the logistic matrix decomposition and sets the prior probabilities of the latent variables to build a Bayesian framework for automatic parameter search. In addition, we construct the variational inference framework of VKBNMF to ensure the solution efficiency. The experimental results show that for the scenarios of paired PPIs, VKBNMF achieves an average AUPR of 0.9101, 0.9316, 0.8727, and 0.9517 on the four benchmark datasets, respectively, and for the scenarios of new human (viral) proteins, VKBNMF still achieves a higher hit rate. The case study also further demonstrated that VKBNMF can be used as an effective tool for the prediction of human-virus PPIs.
PMID:38454139 | DOI:10.1038/s41598-024-56208-w
J Hum Genet. 2024 Mar 7. doi: 10.1038/s10038-024-01235-8. Online ahead of print.
ABSTRACT
A previous study of 200,000 exome-sequenced UK Biobank participants investigating the association between rare coding variants and hyperlipidaemia had implicated four genes, LDLR, PCSK9, APOC3 and IFITM5, at exome-wide significance. In addition, a further 43 protein-coding genes were significant with an uncorrected p value of <0.001. Exome sequence data has become available for a further 270,000 participants and weighted burden analysis to test for association with hyperlipidaemia was carried out in this sample for the 47 genes highlighted by the previous study. There was no evidence to implicate IFITM5 but LDLR, PCSK9, APOC3, ANGPTL3, ABCG5 and NPC1L1 were all statistically significant after correction for multiple testing. These six genes were also all exome-wide significant in the combined sample of 470,000 participants. Variants impairing function of LDLR and ABCG5 were associated with increased risk whereas variants in the other genes were protective. Variant categories associated with large effect sizes are cumulatively very rare and the main benefit of this kind of study seems to be to throw light on the molecular mechanisms impacting hyperlipidaemia risk, hopefully supporting attempts to develop improved therapies.
PMID:38454133 | DOI:10.1038/s10038-024-01235-8
Sci Rep. 2024 Mar 7;14(1):5603. doi: 10.1038/s41598-024-56317-6.
ABSTRACT
Lupus nephritis (LN) is kidney involvement of systematic lupus erythematous that ranges from mild to severe and occurs in 60% of adult patients. Despite advances in therapy, LN morbidity and mortality remains high. There is a paucity of data regarding adult LN patient’s treatment outcome, survival status, and associated factors in developing countries, particularly in Ethiopia. This study aimed to assess the treatment outcome, survival status, and associated factors of adult patients treated for LN in two selected tertiary hospitals [Tikur Anbessa Specialized Hospital (TASH) and St. Paul’s Hospital Millennium Medical College (SPHMMC)] of Addis Ababa, Ethiopia. A hospital-based retrospective cross-sectional multicenter study was conducted from January 1, 2016 to January 1, 2021. Socio-demographic, clinical, and treatment-related data were collected from patient’s medical records by using a structured abstraction checklist. Descriptive statistics were used to summarize the quantitative data as appropriate. The modified Aspreva Lupus Management Study (mALMS) criteria was applied to categorize LN treatment outcomes into complete, partial, and non-response. Multinomial logistic regression analysis was performed to identify predictors of LN treatment outcome. Patients’ survival was estimated by using Kaplan-Meier and Cox proportion regression analysis. P value < 0.05 was considered to declare statistical significance. A total of 200 LN patients were included in the final analysis. Amongst these, the majority of them (91.5%) were females. The median age of the patients was 28 (15-60) years. The mean duration of treatment follow-up was 28 months. The commonly prescribed immunosuppressive drugs during both the induction (49.5%) and maintenance (60%) phases were a combination of mycophenolate mofetil with prednisolone. Complete, partial, and non-responses at the last follow-up visit accounted for 66.5%, 18.0%, and 15.5%, respectively. Patient survival at the last follow-up visit was more than 90% for patients with complete response to the induction therapy. Non-response at the last follow-up visit was significantly associated with severe disease activity index (adjusted odds ratio [AOR] = 6.25, 95% confidence interval [CI] 1.49-26.10), presence of comorbidity (AOR = 0.21, 95% CI 0.05-0.92), baseline leucopenia (AOR = 14.2, 95% CI 1.04-201.3), partial response at the end of induction therapy (AOR = 32.63, 95% CI 1.4-736.0), and duration of induction therapy of greater than 6 months (AOR = 19.47, 95% CI 1.5-258.8). This study unveiled that lower numbers of LN patients were presented with non-response at the last follow-up visit and non-response to induction therapy was associated with lower patients’ survival rates compared with complete or partial response.
PMID:38454130 | DOI:10.1038/s41598-024-56317-6
Nat Med. 2024 Mar 7. doi: 10.1038/s41591-024-02837-7. Online ahead of print.
ABSTRACT
Survivors of childhood cancer are at increased risk for subsequent cancers attributable to the late effects of radiotherapy and other treatment exposures; thus, further understanding of the impact of genetic predisposition on risk is needed. Combining genotype data for 11,220 5-year survivors from the Childhood Cancer Survivor Study and the St Jude Lifetime Cohort, we found that cancer-specific polygenic risk scores (PRSs) derived from general population, genome-wide association study, cancer loci identified survivors of European ancestry at increased risk of subsequent basal cell carcinoma (odds ratio per s.d. of the PRS: OR = 1.37, 95% confidence interval (CI) = 1.29-1.46), female breast cancer (OR = 1.42, 95% CI = 1.27-1.58), thyroid cancer (OR = 1.48, 95% CI = 1.31-1.67), squamous cell carcinoma (OR = 1.20, 95% CI = 1.00-1.44) and melanoma (OR = 1.60, 95% CI = 1.31-1.96); however, the association for colorectal cancer was not significant (OR = 1.19, 95% CI = 0.94-1.52). An investigation of joint associations between PRSs and radiotherapy found more than additive increased risks of basal cell carcinoma, and breast and thyroid cancers. For survivors with radiotherapy exposure, the cumulative incidence of subsequent cancer by age 50 years was increased for those with high versus low PRS. These findings suggest a degree of shared genetic etiology for these malignancy types in the general population and survivors, which remains evident in the context of strong radiotherapy-related risk.
PMID:38454124 | DOI:10.1038/s41591-024-02837-7
Sci Rep. 2024 Mar 7;14(1):5680. doi: 10.1038/s41598-024-56399-2.
ABSTRACT
The world suffers from the acute respiratory syndrome COVID-19 pandemic, which will be scary if other co-existing illnesses exacerbate it. The co-occurrence of the COVID-19 virus with kidney disease has not been available in the literature. So, further research needs to be conducted to reveal the transmission dynamics of COVID-19 and kidney disease. This study aims to create mathematical models to understand how COVID-19 interacts with kidney diseases in specific populations. Therefore, the initial step was to formulate a deterministic Susceptible-Infected-Recovered (SIR) mathematical model to depict the co-infection dynamics of COVID-19 and kidney disease. A mathematical model with seven compartments has been developed using nonlinear ordinary differential equations. This model incorporates the invariant region, disease-free and endemic equilibrium, along with the positivity solution. The basic reproduction number, calculated via the next-generation matrix, allows us to assess the stability of the equilibrium. Sensitivity analysis is also utilised to understand the influence of each parameter on disease spread or containment. The results show that a surge in COVID-19 infection rates and the existence of kidney disease significantly enhances the co-infection risks. Numerical simulations further clarify the potential outcomes of treating COVID-19 alone, kidney disease alone, and co-infected cases. The study of the potential model can be utilised to maximise the benefits of simulation to minimise the global health complexity of COVID-19 and kidney disease.
PMID:38454115 | DOI:10.1038/s41598-024-56399-2
Sci Rep. 2024 Mar 7;14(1):5592. doi: 10.1038/s41598-024-56335-4.
ABSTRACT
To provide evidence for optimization of multi-kinase inhibitors (MKIs) use in the clinic, we use the public database to describe and evaluate electrolyte disorders (EDs) related to various MKIs treated for renal cell carcinoma. We analyzed spontaneous reports submitted to the Food and Drug Administration Adverse Events Reporting System (FAERS) in an observational and retrospective manner. Selecting electrolyte disorders’ adverse events to multikinase inhibitors (axitinib, cabozantinib, lenvatinib, pazopanib, sunitinib, and sorafenib). We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms to analyze suspected adverse reactions of electrolyte disorders induced by MKIs (which were treated for renal cell carcinoma) between January 2004 and December 2022. As of December 2022, 2772 MKIs (which were treated for renal cell carcinoma) ICSRs were related to electrolyte disorders AEs. In general, there were more AEs cases in males, except lenvatinib and 71.8% of the cases were submitted from North America. ICSRs in this study, the age group most frequently affected by electrolyte disorders AEs was individuals aged 45-64 years for axitinib, cabozantinib, pazopanib, and sunitinib, whereas electrolyte disorders AEs were more common in older patients (65-74 years) for sorafenib and lenvatinib. For all EDs documented in ICSRs (excluding missing data), the most common adverse outcome was hospitalization(1429/2674, 53.4%), and the most serious outcome was death/life-threat(281/2674, 10.5%). The prevalence of mortality was highest for sunitinib-related EDs (145/616, 23.5%), excluding missing data (n = 68), followed by cabozantinib-related EDs (20/237, 8.4%), excluding missing data (n = 1). The distribution of time-to-onset of Each drug-related ICSRs was not all the same, and the difference was statistically significant (P = 0.001). With the criteria of ROR, the six MKIs were all significantly associated with electrolyte disorders AEs, the strongest association was the association between cabozantinib and hypermagnesaemia. MKIs have been reported to have significant electrolyte disorders AEs. Patients and physicians need to recognize and monitor these potentially fatal adverse events.
PMID:38454105 | DOI:10.1038/s41598-024-56335-4
Sci Rep. 2024 Mar 7;14(1):5677. doi: 10.1038/s41598-024-56387-6.
ABSTRACT
Hypertension is a disease closely related to inflammation, and the systemic immunity-inflammation index (SII) is a new and easily detectable inflammatory marker. We aimed to investigate the association between SII and hypertension risk in a adult population in the US. We utilized data from the National Health and Nutrition Examination Survey spanning from 1999 to 2018, incorporating comprehensive information from adults reporting hypertension. This included details on blood pressure monitoring, complete blood cell counts, and standard biochemical results. The SII was computed as the platelet count multiplied by the neutrophil count divided by the lymphocyte count. We employed a weighted multivariate logistic regression model to examine the correlation between SII and hypertension. Subgroup analyses were conducted to explore potential influencing factors. Furthermore, smooth curve fitting and two-piecewise logistic regression analysis were employed to describe non-linear relationships and identify inflection points. This population-based study involved 44,070 adults aged 20-85 years. Following Ln-transformation of the SII, multivariable logistic regression revealed that, in a fully adjusted model, participants in the highest quartile of Ln(SII) had a 12% increased risk of hypertension compared to those in the lowest quartile, which was statistically significant (OR:1.12; 95% CI 1.01, 1.24; P < 0.001), with a P for trend = 0.019. Subgroup analysis indicated no significant interactions between Ln(SII) and specific subgroups except for the body mass index subgroup (all P for interaction > 0.05). Additionally, the association between Ln(SII) and hypertension displayed a U-shaped curve, with an inflection point at 5.89 (1000 cells/μl). Based on this research result, we found a U-shaped correlation between elevated SII levels and hypertension risk in American adults, with a inflection point of 5.89 (1000 cells)/μl). To validate these findings, larger scale prospective surveys are needed to support the results of this study and investigate potential mechanisms.
PMID:38454104 | DOI:10.1038/s41598-024-56387-6
Eval Program Plann. 2024 Feb 24;103:102414. doi: 10.1016/j.evalprogplan.2024.102414. Online ahead of print.
ABSTRACT
Brazil ranked third in the number of Monkeypox infected worldwide in early September 2022 and eighth in multiple deaths. Brazilian Ministry of Health prepared a public policy to face the smallpox outbreak. This paper aims to analyze the governmental public policy’ impacts on Monkeypox using survival analysis. The information in the database was collected from epidemiological bulletins on the official websites of the Brazilian Ministry of Health and the World Health Organization (WHO). The survival analysis with parametric statistical analysis, semiparametric with Cox regression, and nonparametric analysis were used. The inference of causality was perceived by the impact caused by the national public policy with the proportional reduction in the number of cases in the treatment group (Chi-sq = 117.783, p < 0.001), contrary to what was perceived in the control group, as well as survival about the time of the states that elaborated their plans based on what was made available by the government. The need to evaluate government projects should be within the scope of project management in Brazilian states and provide for more assertive decision-making in the fight against smallpox.
PMID:38452410 | DOI:10.1016/j.evalprogplan.2024.102414
Gen Hosp Psychiatry. 2024 Feb 15;88:23-29. doi: 10.1016/j.genhosppsych.2024.02.006. Online ahead of print.
ABSTRACT
OBJECTIVE: A cluster randomized controlled trial (RCT) of two interventions for addressing perinatal depression treatment in obstetric settings was conducted. This secondary analysis compared treatment referral and participation among Minoritized perinatal individuals compared to their non-Hispanic white counterparts.
METHODS: Among perinatal individuals with depression symptoms, we examined rates of treatment 1) referral (i.e., offered medications or referred to mental health clinician), 2) initiation (i.e., attended ≥1 mental health visit or reported prescribed antidepressant medication), and 3) sustainment (i.e., attended >1 mental health visit per study month or prescribed antidepressant medication at time of study interviews). We compared non-Hispanic white (NHW) (n = 149) vs. Minoritized perinatal individuals (Black, Asian, Hispanic/Latina, Pacific Islander, Native American, Multiracial, and white Hispanic/Latina n = 157). We calculated adjusted odds ratios (aOR) for each outcome.
RESULTS: Minoritized perinatal individuals across both interventions had significantly lower odds of treatment referral (aOR = 0.48;95% CI = 0.27-0.88) than their NHW counterparts. There were no statistically significant differences in the odds of treatment initiation (aOR = 0.64 95% CI:0.36-1.2) or sustainment (aOR = 0.54;95% CI = 0.28-1.1) by race/ethnicity.
CONCLUSIONS: Perinatal mental healthcare inequities are associated with disparities in treatment referrals. Interventions focusing on referral disparities across race and ethnicity are needed.
PMID:38452405 | DOI:10.1016/j.genhosppsych.2024.02.006