RESUMEN

Background: A high body mass index (BMI) increases the risk of hypertension. However, little is known about the dose-dependent association between BMI and hypertension. Therefore, this study investigated the prevalence of hypertension in 7568 subjects from the Jiangsu Province, Eastern China, and analyzed the dose-response relationship between BMI and hypertension risk. Methods: The eligible subjects completed a structured questionnaire and clinical biochemical indicators were measured according to standardized protocols. Multivariate logistic regression models were used to evaluate the association between BMI and hypertension. Restricted cubic spline (RCS) analysis was used to analyze the dose-response relationship between BMI and hypertension risk. Moreover, sensitivity analysis was performed to verify the robustness of our findings. Results: The prevalence of hypertension was 35.3 % in the total population. BMI was significantly associated with systolic and diastolic blood pressure. The fully-adjusted odds ratio (OR) with 95 % confidence interval (CI) for hypertension was 1.17 (1.15, 1.19) for every 1 kg/m2 increase in BMI. Furthermore, the OR (95 % CI) for hypertension in the highest BMI group (Obesity) was 4.14 (3.45, 4.96) after adjusting for covariates compared with the normal group. Multivariable adjusted RCS analysis showed a positive and linear dose-response relationship between BMI and hypertension risk both in male and female populations (all P for non-linearity > 0.05). Conclusion: Our study demonstrated a positive and linear dose-response relationship between BMI and the risk of hypertension. The results of this study provide evidence for BMI-related clinical interventions to reduce the risk of hypertension.

RESUMEN

OBJECTIVES: This meta-analysis aimed to explore the relationship between the dose of acupuncture sessions, acupuncture frequency, and acupuncture duration and its effects on migraine. METHODS: Eight databases were searched for randomized controlled trials (RCTs) evaluating the efficacy of penetrating manual acupuncture for migraine published in English and Chinese from inception to June 20, 2024. The robust-error meta-regression (REMR) approach and non-linear meta-regression with restricted cubic spline (RCS) were used to investigate the dose-response association between acupuncture sessions, acupuncture frequency, and acupuncture duration and the frequency of migraine attacks. The potential nonlinear relationships was tested by restricting the regression coefficient to zero and a P value＜0.1. The statistical analysis was conducted using Stata 17.0. The risk of bias was independently assessed by two reviewers using the Cochrane tool. The reporting quality for acupuncture procedures was evaluated by STRICTA criteria. RESULTS: Thirty-two RCTs involving 1562 participants were included, and the results showed a J-shaped dose-response association between acupuncture sessions, acupuncture frequency, and acupuncture duration and migraine attack frequency. After 16 acupuncture sessions, the change in the frequency of migraine attacks was 3.95 (95%CI: 3.13 to 4.77). Three sessions of acupuncture a week resulted in a significant decrease in the frequency of migraine attacks, reaching 4.04 (95% CI: 2.49 to 5.58). After two months of acupuncture, the frequency of migraine attacks decreased significantly, showing a difference of 4.05 (95% CI: 3.61 to 4.49). Subsequently, the improvement trend gradually flattened, yielding diminishing benefits to patients. The risk of bias showed that seven studies were rated as "low risk", two were rated as "high risk", and the others were rated as "unclear risk". The reporting quality of RCTs of acupuncture for migraine remain suboptimal. CONCLUSIONS: A non-linear dose-response relationship was found between acupuncture sessions, acupuncture frequency, and acupuncture duration and migraine attack frequency. The results of our study recommend 16 sessions of acupuncture with a frequency of 3 sessions/week and a treatment duration of 1.5 to 2 months. REGISTRATION NUMBER: This meta-analysis has been registered on PROSPERO (CRD42023400493).

RESUMEN

The current radiation dose estimates used in medical imaging, radiation oncology or environmental assessments are not entirely accurate from a fundamental physics perspective, let alone for biological consequences. The "one cloth fits all" approach of radiation-matter interactions cannot assess the effects of interactions of the same species of radiation of different energies on the same isotope of an element. Preliminary steps to set the radiation dosimetry in the right direction are suggested.

RESUMEN

Background and purpose: Lung cancer is a leading cause of cancer-related mortality, and stereotactic body radiotherapy (SBRT) has become a standard treatment for early-stage lung cancer. However, the heterogeneous response to radiation at the tumor level poses challenges. Currently, standardized dosage regimens lack adaptation based on individual patient or tumor characteristics. Thus, we explore the potential of delta radiomics from on-treatment magnetic resonance (MR) imaging to track radiation dose response, inform personalized radiotherapy dosing, and predict outcomes. Materials and methods: A retrospective study of 47 MR-guided lung SBRT treatments for 39 patients was conducted. Radiomic features were extracted using Pyradiomics, and stability was evaluated temporally and spatially. Delta radiomics were correlated with radiation dose delivery and assessed for associations with tumor control and survival with Cox regressions. Results: Among 107 features, 49 demonstrated temporal stability, and 57 showed spatial stability. Fifteen stable and non-collinear features were analyzed. Median Skewness and surface to volume ratio decreased with radiation dose fraction delivery, while coarseness and 90th percentile values increased. Skewness had the largest relative median absolute changes (22 %-45 %) per fraction from baseline and was associated with locoregional failure (p = 0.012) by analysis of covariance. Skewness, Elongation, and Flatness were significantly associated with local recurrence-free survival, while tumor diameter and volume were not. Conclusions: Our study establishes the feasibility and stability of delta radiomics analysis for MR-guided lung SBRT. Findings suggest that MR delta radiomics can capture short-term radiographic manifestations of the intra-tumoral radiation effect.

RESUMEN

BACKGROUND: Patients not mechanically ventilated often fail to achieve the recommended duration of awake prone positioning due to treatment interruption and discomfort. Few studies have investigated the link between treatment outcome and prone-positioning duration, the inability to accurately guide patients to perform awake prone positioning. OBJECTIVES: The aim of this study was to characterise and explore the relationship between awake prone-positioning duration with the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2 [P/F]) changes and the risk of disease aggravation. METHODS: A prospective cohort study; dose-response relationship was used. Awake prone positioning was performed on patients with severe Corona Virus Disease 2019 (COVID-19) for 5 consecutive days from 1 February to 21 March 2023. Linear and logistic regression models were utilised to assess the association between prone-positioning duration with P/F changes and risk of disease aggravation, respectively. Meanwhile, the restricted cubic spline was used to evaluate the dose-response relationships. RESULTS: A total of 408 patients with severe COVID-19 were analysed. The daily prone positioning duration was 4.57 ± 2.74 h/d, and the changes in P/F were 67.63 ± 69.17 mmHg. On the sixth day of hospitalisation, the condition of 52 (12.8%) patients deteriorated. There was a positive, nonlinear dose-response relationship (Poverall < 0.001, Pnonlinearity = 0.041) and a strong, significant positive correlation (ß = 29.286, t = 4.302, P < 0.001) between the prone-positioning duration and P/F changes. The risk of disease aggravation gradually decreases with the increase of prone-positioning duration. Nonetheless, the prone-positioning duration was not statistically associated with disease aggravation (odds ratio = 0.986, 95% confidence interval: 0.514-1.895). CONCLUSIONS: Awake prone positioning for ≥4 h/d is effective on oxygenation (not mortality/intubation) and is achievable for patients with severe COVID-19. Prolonged prone positioning is promising in improving patients' oxygenation but does not alleviate their risk of disease aggravation.

RESUMEN

OBJECTIVE: Epilepsy, a neurological disorder, is identified by the presence of recurrent seizures. We aimed to detect dietary fiber intake and its association with epilepsy prevalence in U.S. adults. METHODS: This cross-sectional study obtained data from the 2013-2018 National Health and Nutrition Examination Survey database. Univariate and multivariate logistic regression models were employed to estimate the association between dietary fiber intake and epilepsy prevalence. The restricted cubic spline (RCS) model was also applied to investigate the dose-response relationships between dietary fiber intake and epileptic seizure events(ESEs). RESULTS: Our final sample included 13,277 NHANES participants, with the average prevalence of ESEs being 1.09 % (145/13277). After adjusting for all confounding factors, the third quartile of dietary fiber intake levels remained significantly associated with a decreased risk of ESEs[odds ratios (OR) 0.54,95 % confidence interval (CI) 0.33-0.88, P = 0.014)] compared to the first quartile. Higher fiber intake indicated a stable negative association with ESEs in the multivariate logistic regression analysis, weighted generalized additive model. A nonlinear dose-response relationship was observed between dietary fiber intake levels and decreased ESEs risk (P for overall=0.017, P for nonlinear=0.155). Interaction tests showed no significant effect of demographic and disease status on the association between dietary fiber intake and ESEs. CONCLUSION: In this cross-sectional study, people with a high dietary fiber intake were at a reduced risk of ESEs. However, further prospective studies are needed to investigate the effect of dietary fiber intake in epilepsy events and to determine causality.

RESUMEN

How to improve the growth efficiency of microalgae is the bottleneck of microalgae large-scale application. The addition of trace substances can promote the growth of microalgae, but there is no suitable model that can be used to predict the effects of trace substance concentrations on the growth of microalgae. In the present study, a mathematical model based on hormesis is proposed to describe the effects produced by trace substances on the biomass of microalgae and applied to assess the dose-response of four phytohormones on Scenedesmus sp. LX1 with a high coefficient of determination (R2 ≥ 0.90). Several new mathematical parameters, such as starting effective dose (SD), inflection point dose (PD), concentration for 0 % of maximal effect, end effective dose (ED), maximum stimulatory effect (MSE), and maximum inhibitory effect (MIE), were extracted and useful to help researchers in applying trace substances to assist in the production of microalgal biomass for data reference and prediction. In concrete terms, the above model parameters can be well applied to screen the trace substances, dominant algal species and determine the concentration range. This study provides valuable insights into the potential of using phytohormones to enhance the biomass production of microalgae and offers a new approach to optimizing the culture of microalgae.

RESUMEN

OBJECT: This study investigated changes in methylation levels within the Glutathione peroxidase 3 (GPX3) promoter region among patients diagnosed with Chronic Heart Failure (CHF). Peripheral blood samples were collected from 20 CHF patients and 20 healthy individuals for analysis. METHODS: Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, methylation levels of 11 CpG sites within the GPX3 promoter region were quantified. RESULTS: Results showed a significant increase in methylation at the GPX3_FA10_CpG_24 site in CHF patients compared to the control group (P < 0.05). Furthermore, a nonlinear dose-response relationship was observed between methylation levels at this site and key clinical parameters including serum apolipoprotein A-1, D-dimer, Chlorine(Cl), Potassium(K), and Sodium(Na) (P < 0.05). CONCLUSIONS: These findings suggest that aberrant methylation of GPX3 promoter may impact disease progression by influencing physiological functions such as blood lipids, coagulation, and electrolytes. Further investigations are warranted to elucidate the role of GPX3 promoter methylation in CHF pathogenesis, potentially contributing valuable insights for its prevention, diagnosis, and treatment.

RESUMEN

Aphis gossypii Glover is one of the most agriculturally important phloem-feeding economic pests, causing tremendous loss in crop yield annually. The hormesis is an important cause of A. gossypii resistance formation, population resurgence, and re-outbreak. However, whether the hormesises induced by different insecticides interact mutually remain largely unclear. In the study, four-generation A. gossypii experiment found that the 24-h sublethal-dose (LC20) sulfoxaflor treatment on G0 significantly increased the net reproductive rate (R0) and fecundity of G1 and G2 generation A. gossypii, but it did not significantly affect the fecundity of G3 and G4 individuals. Transcriptomic analyses revealed that the insecticide-induced significant up-regulation of pathways ribosome, energy metabolism, and the DNA replication and reparation might be responsible for the enhancement of fecundity in G1 and G2 A. gossypii. Notably, G0 exposure to LC20 sulfoxaflor followed by G1 exposure to LC30 deltamethrin resulted in a stronger reproductive stimulation than sulfoxaflor or deltamethrin exposure alone. Our findings provide valuable reference for optimizing sulfoxaflor application in integrated pest management strategies.

Asunto(s)

RESUMEN

Ozone is the most damaging air pollutant to vegetation globally. Metrics of accumulated ozone above a concentration threshold (e.g. AOT40, ppb·h) have been widely used to assess ozone risk. However, there is growing consensus that accumulated Phytotoxic Ozone Dose (POD) above a receptor-specific critical stomatal flux threshold (y; nmol O3 m-2 s-1), expressed per unit of projected leaf area, provides a more reliable risk assessment, as it considers ozone entering the leaf (PODy, mmol m-2 leaf area). Few studies have assessed both concentration- and flux-based metrics using site-specific observations of ozone and meteorology. In this study we assessed the risk that ozone poses to five vegetation types across eight sites in Ireland during 2005-2021, using AOT40 and PODy risk metrics, and we predicted impacts using dose-response relationships. Long-term trends in both metrics were also assessed. The PODy critical level for vegetation protection was exceeded for all vegetation types, with exceedances most common at Atlantic coastal sites, and for tree species (beech POD1 15.7-25.7 mmol/m2 PLA). When PODy and AOT40 results were normalised based on their respective critical levels, predicted impacts were higher for PODy. There were significant increases in PODy for three vegetation types at rural sites during the study period, which also experienced increases in temperature and global solar radiation. The long-term trends were consistent with other European studies that show decreases in AOT40 and increases in PODy. While ozone concentrations in Ireland are relatively low (39-75 µg/m3 five-year average range), the humid climate and longer growing season may lead to elevated stomatal ozone uptake and thereby a risk to vegetation.

RESUMEN

PURPOSE: Several studies have shown that aerobic exercise training improves obstructive sleep apnea (OSA) severity. However, a dose-response relationship has never been shown. This study aimed to quantify any dose-response relationships between time spent per week in aerobic exercise and key sleep apnea outcomes. METHODS: Randomized controlled trials (RCT) were selected from literature search studying the effects of supervised aerobic exercise training on patients with OSA. Dose-response meta-analyses were performed, where the 'dose' was the total weekly duration of aerobic exercise training. Primary outcomes were apnea hypopnea index (AHI), cardiorespiratory fitness (maximum oxygen consumption or VO2peak) and Epworth Sleepiness Scale (ESS). RESULTS: Analysis of data from 11 RCTs showed a non-linear dose-response relationship between the total weekly duration of aerobic exercise training and mean differences in AHI. Maximum effects on AHI (-10.92 (95%CIs: -15.57; -6.27)) were observed when the weekly duration of aerobic exercise reached 100 min/week. Similar non-linear dose-response trend was observed in the mean differences in VO2peak. Studies in which aerobic exercise training lasted ≥ 12 weeks showed greater proportional changes in mean AHI differences with maximal effects reaching a peak at ∼ 70 min/week of aerobic exercise training. ESS and total weekly duration of aerobic exercise training showed a linear dose-response relationship based on 4 RCTs. CONCLUSIONS: Based on these analyses, aerobic exercise training of 70-100 min/week over 3 or 5 days a week should be recommended as adjunctive treatment for patients with OSA.

RESUMEN

A burgeoning body of epidemiological and toxicological evidence suggests that thyroid health may be significantly impacted by exposure to both long- and short-chain perfluoroalkyl substances (PFAS) compounds. We conducted a meta-analysis to examine the association between 16 PFAS compounds and five thyroid hormones (TSH, TT3, TT4, FT3, and FT4) in the serum of a pregnant women, adolescents, and adults. The dose-response relationship between some PFAS and thyroid hormones in different population subpopulation was found and the model was fitted. We also amalgamated data from 18 animal experiments with previously published in vitro studies to elucidate the toxicological mechanisms underlying the impact of PFAS on the thyroid gland. The results of the study showed that (a) both conventional and emerging PFAS compounds were identified in human samples and exhibited associations with thyroid health outcomes; (b) in animal studies, PFAS have been found to impact thyroid gland health through two primary mechanisms: by influencing the hypothalamic-pituitary-thyroid axis and by binding to thyroid receptors. This study provides a systematic description of the health effects and risk assessment associated with PFAS exposure on the thyroid gland. Furthermore, dose-response relationships were established through the Hill model in python.

RESUMEN

Metabolic adaptations early in life can drive energy expenditure towards brain and physical development, with less emphasis on body mass gain and somatic growth. Dietary or pharmacological manipulations can influence these processes, but to date, the effects provided by riboflavin have not been studied. The study aimed to evaluate the effects of neonatal treatment with different doses of riboflavin on sensorimotor and somatic development in rodents. Based on this, the following experimental groups were formed: Control (C, 0 mg/kg), Riboflavin 1 (R1, 1 mg/kg), Riboflavin 2 (R2, 10 mg/kg) and Riboflavin 3 (R3, 100 mg/kg). Treatment with 100 mg/kg riboflavin anticipated the reflex ontogeny of righting, cliff aversion, negative geotaxis, and free-fall righting. Intervention with 10 and 100 mg/kg of riboflavin anticipated the reflex maturation of vibrissae placement. Eye-opening, upper incisor eruption, and lower incisor eruption reached maturational age more quickly for animals treated with 100 mg/kg, while caudal growth and body weight gain were reduced from the second week of treatment, for groups R2 and R3. Pearson's correlation analysis indicated a positive association between the administration of high doses of riboflavin and murine growth in the first week of treatment. There was, however, a negative association between treatment with a high dose of riboflavin and growth in the second week of administration, coinciding with a reduction in body weight gain in the R3 group. Treatment with 100 mg/kg of riboflavin also reduced energy expenditure parameters in the open field and catwalk. Although high-dose treatment stimulates the physiological plasticity of the CNS and reduces weight gain, hepatic parameters were preserved, highlighting the participation of the liver in the supply of fatty acids for neural maturation. Furthermore, hypothalamic NRF-1 expression was increased in the R3 group inversely to the reduction in weight gain. Our results suggest that high-dose riboflavin stimulates sensorimotor and somatic development and reduces the energy invested in growth, body weight gain, and locomotor activity, possibly involving NRF-1 gene modulation in the hypothalamus.

RESUMEN

Purpose: This cross-sectional study conducted in the general US population investigated the association between dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the prevalence of AMD. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) were utilized, including 4,842 participants aged 40 years and older. Dietary EPA and DHA intake data were collected through two 24-h dietary recall interviews and adjusted for weight. AMD was determined by a standardized grading system based on the presence of key features of AMD in color photographs of the macula. Multivariate logistic regression and restricted cubic spline models evaluated the associations between dietary EPA and DHA intake and AMD. Subgroup analysis and interaction analysis explored the influence of covariates. Results: A total of 4,842 participants were included. In the multivariate-adjusted model 2, the odds ratios (ORs) with 95% confidence intervals (CIs) for AMD were 0.86 (0.75, 0.99) and 0.88 (0.80, 0.97) per unit increase in dietary EPA and DHA intake, respectively. Interaction testing revealed significant effect modification by age, education, and BMI on the EPA-AMD association, indicating these factors significantly impacted this inverse relationship (p-interaction < 0.05). Similarly, age, education, BMI, and cataract surgery history modified the inverse DHA-AMD association (p-interaction < 0.05). Dose-response analyses demonstrated a negative correlation between dietary EPA and DHA intake with AMD prevalence (p-nonlinearity = 0.184 and 0.548, respectively). Conclusion: Our findings suggested that higher dietary EPA and DHA intake could be associated with lower AMD risk in older US adults. Age, education level, BMI, and history of cataract surgery may influence this inverse association.

RESUMEN

BACKGROUND: Previous studies have shown significant associations between individual fat-soluble vitamins (FSVs) and metabolic syndromes (MetS). However, evidence on the multiple FSVs co-exposure and MetS odds is limited. Given that individuals are typically exposed to different levels of FSVs simultaneously, and FSVs can interact with each other. It's necessary to explore the association between multiple FSVs co-exposure and MetS odds. This study aims to address this gap in general U.S. adults aged ≥ 20 years. METHODS: We conducted a cross-sectional study utilizing data from the National Health and Nutrition Examination Surveys (NHANESs) 2003-2006 and 2017-2018. Three FSV, including vitamin A (VA), vitamin E (VE), and vitamin D (VD), and MetS diagnosed according to the ATP III guidelines were selected as exposure and outcome, respectively. Multivariable-adjusted logistic model was used to explore the associations of individual FSV exposure with MetS odds and MetS components. Restricted cubic splines were performed to explore the dose-response relationships among them. The quantile g-computation method was adopted to explore the associations of multiple FSVs co-exposure with MetS odds and MetS components. RESULTS: The presented study included a total of 13,975 individuals, with 2400 (17.17%) were diagnosed with MetS. After adjusting for various confounders, a positive linear pattern was observed for serum VA and VE and MetS associations. Serum VD was found to be negatively associated with MetS in a linear dose-response way. For each component of MetS, higher serum VA and VE were associated with higher triglyceride and high-density lipoprotein; higher serum VD was negatively associated with triglyceride, blood pressure, and fasting plasma glucose. MetS odds increased by 15% and 13%, respectively, in response to one quartile increase in FSVs co-exposure index (qgcomp) in the conditional model (OR = 1.15, 95%CI: 1.06, 1.24) and the marginal structural model (OR = 1.13, 95%CI: 1.06, 1.20). Besides, co-exposure to VA, VE, and VD was positively associated with triglyceride, high-density lipoprotein, and blood pressure levels. CONCLUSION: Findings in the present study revealed that high serum VA and VE levels were associated with elevated MetS odds, while serum VD was inversely associated with MetS odds. FSVs co-exposure was positively associated with MetS odds.

Asunto(s)

RESUMEN

Background: Recurrent acute myocardial infarction requiring unplanned percutaneous coronary intervention (PCI) is one of the major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS) after PCI. There is a continuing controversy about the association between serum cystatin C, a biomarker for the evaluation of renal function, and the prognosis of ACS patients following PCI. The retrospective study evaluated the association between serum cystatin C level and MACE in ACS patients after PCI. Methods: Data were retrieved for 330 patients with ACS for primary PCI in a single center. Serum cystatin C levels were measured before PCI. All patients underwent regular follow-ups after PCI, and the studied endpoint was MACE, defined as the need for a repeat revascularization in the heart. The predictive value of serum cystatin C for MACE was analyzed using univariate and multivariate analysis. Restricted cubic spline (RCS) analysis was applied to evaluate the dose-response relationship between serum cystatin C level and MACE in ACS patients following PCI. Results: After a median follow-up of 63 months (range, 1-148 months), 121 of the 330 patients experienced MACE. Compared to patients who did not have MACE, patients who had MACE showed a significant decrease in serum cystatin C levels (0.99±0.32 vs. 1.15±0.78 mg/L, P=0.03). In multivariate regression analysis, serum cystatin C level was an independent risk factor for MACE. According to the serum cystatin C level, patients were divided into 4 categories, Cox regression analysis illustrated that the second quartile of serum cystatin C level indicated an increased risk of MACE in patients with PCI for primary ACS compared to the highest quartile [Q2: adjusted hazard ratio (HR) =2.109; 95% confidence interval (CI): 1.193-3.727; P=0.01]. RCS analysis showed a significant U-shaped dose-response relationship between cystatin C level and MACE in patients with PCI for ACS (P for non-linearity =0.004). Conclusions: These results indicated an association between serum cystatin C level and post-PCI MACE in ACS patients.

RESUMEN

Plastic pollution, driven by micro- and nanoplastics (MNPs), poses a major environmental threat, exposing humans through various routes. Despite human colorectal adenocarcinoma Caco-2 cells being used as an in vitro model for studying the intestinal epithelium, uncertainties linger about MNPs harming these cells and the factors influencing adverse effects. Addressing this lacuna, our study aimed to elucidate the pivotal MNP parameters influencing cytotoxicity in Caco-2 cells, employing meta-analysis and machine learning techniques for quantitative assessment. Initial scrutiny of 95 publications yielded 17 that met the inclusion criteria, generating a dataset of 320 data points. This dataset underwent meticulous stratification based on polymer type, exposure time, polymer size, MNP concentration, and biological assays utilised. Subsequent dose-response curve analysis revealed moderate correlations for selected subgroups, such as the (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) MTT biological assay and exposure time exceeding 24 hours, with coefficient of determination (R2) values of 0.50 (p-value: 0.0065) and 0.60 (p-value: 0.0018) respectively. For the aforementioned two subgroups, the MNP concentrations surpassing 10 µg/mL led to diminished viability of Caco-2 cells. Notably, we observed challenges in employing meta-analysis to navigate this multidimensional MNP dataset. Leveraging a random forest model, we achieved improved predictive performance, with R2 values of 0.79 and a root mean square error (RMSE) of 0.14 for the prediction of the Log Response Ratio on the test set. Model interpretation indicated that size and concentration are the principal drivers influencing Caco-2 cell cytotoxicity. Additionally, the partial dependence plot illustrating the relationship between the size of MNPs and predicted cytotoxicity reveals a complex pattern. Our study provides crucial insights into the health impacts of plastic pollution, informing policymakers for targeted interventions, thus contributing to a comprehensive understanding of its human health consequences.

RESUMEN

A common problem in clinical trials is to test whether the effect of an explanatory variable on a response of interest is similar between two groups, for example, patient or treatment groups. In this regard, similarity is defined as equivalence up to a pre-specified threshold that denotes an acceptable deviation between the two groups. This issue is typically tackled by assessing if the explanatory variable's effect on the response is similar. This assessment is based on, for example, confidence intervals of differences or a suitable distance between two parametric regression models. Typically, these approaches build on the assumption of a univariate continuous or binary outcome variable. However, multivariate outcomes, especially beyond the case of bivariate binary responses, remain underexplored. This paper introduces an approach based on a generalized joint regression framework exploiting the Gaussian copula. Compared to existing methods, our approach accommodates various outcome variable scales, such as continuous, binary, categorical, and ordinal, including mixed outcomes in multi-dimensional spaces. We demonstrate the validity of this approach through a simulation study and an efficacy-toxicity case study, hence highlighting its practical relevance.

Asunto(s)

RESUMEN

Many studies have demonstrated that long double-stranded RNAs (dsRNAs) targeting essential genes of white spot syndrome virus (WSSV) can induce a sequence-specific antiviral RNA interference (RNAi) response in shrimp, thereby offering protection against WSSV infection. However, further experimental data on the required dose of dsRNAs and the duration of protection from a single administration are necessary to establish RNAi-mediated methods as effective and practical antiviral measures. In this study, we evaluated the protective efficacy and the duration of protection provided by a single administration of various doses of long dsRNA targeting WSSV ribonucleotide reductase 2 (rr2) in white-leg shrimp Litopenaeus vannamei. The protective efficacy of long dsRNA targeting WSSV rr2 was not diminished by the reduction of the dose to 100 ng g-1 of body weight, suggesting that a relatively low dose can effectively induce an RNAi response in shrimp. Furthermore, shrimp were well-protected against WSSV challenges for up to 4 wk post-administration of the rr2-targeting long dsRNA, although the protective effect almost disappeared at 6 wk post-administration. These results suggest that long dsRNAs can provide protection against WSSV for at least 1 mo, and monthly administration of long dsRNAs could serve as a long-term protective strategy for shrimp against WSSV.

Asunto(s)

RESUMEN

BACKGROUND: Vitamin D supplementation may prevent acute respiratory infections (ARIs). This study aimed to identify the optimal methods of vitamin D supplementation. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry were searched from database inception through July 13, 2023. Randomized-controlled trials (RCTs) were included. Data were pooled using random-effects model. The primary outcome was the proportion of participants with one or more ARIs. RESULTS: The analysis included 43 RCTs with 49320 participants. Forty RCTs were considered to be at low risk for bias. The main pairwise meta-analysis indicated there were no significant preventive effects of vitamin D supplementation against ARIs (risk ratio [RR]: 0.99, 95% confidence interval [CI]: 0.97 to 1.01, I2 = 49.6%). The subgroup dose-response meta-analysis indicated that the optimal vitamin D supplementation doses ranged between 400-1200 IU/day for both summer-sparing and winter-dominant subgroups. The subgroup pairwise meta-analysis also revealed significant preventive effects of vitamin D supplementation in subgroups of daily dosing (RR: 0.92, 95% CI: 0.85 to 0.99, I2 = 55.7%, number needed to treat [NNT]: 36), trials duration < 4 months (RR: 0.81, 95% CI: 0.67 to 0.97, I2 = 48.8%, NNT: 16), summer-sparing seasons (RR: 0.85, 95% CI: 0.74 to 0.98, I2 = 55.8%, NNT: 26), and winter-dominant seasons (RR: 0.79, 95% CI: 0.71 to 0.89, I2 = 9.7%, NNT: 10). CONCLUSION: Vitamin D supplementation may slightly prevent ARIs when taken daily at doses between 400 and 1200 IU/d during spring, autumn, or winter, which should be further examined in future clinical trials.

Asunto(s)