Ultra-processed foods and cardiovascular disease: analysis of three large US prospective cohorts and a systematic review and meta-analysis of prospective cohort studies.

Background: Prospective associations between total and groups of ultra-processed foods (UPF) and cardiovascular disease (CVD) remained to be characterised. Our aim was to assess the association of total and group-specific UPF intakes with CVD, coronary heart disease (CHD), and stroke in three large prospective cohorts of US adults. Additionally, we conducted a systematic review and meta-analyses on the existing evidence on the associations of total UPF intake with these outcomes. Methods: UPF intake was assessed through food frequency questionnaires in the Nurses' Health Study (NHS; n = 75,735), Nurses' Health Study II (NHSII; n = 90,813), and Health Professionals Follow-Up Study (HPFS; n = 40,409). Cox regression estimated cohort-specific associations of total and group-specific UPF intake with risk of CVD (cases = 16,800), CHD (cases = 10,401), and stroke (cases = 6758), subsequently pooled through fixed-effect models. Random-effects meta-analyses pooled existing prospective findings on the UPF-CVD association identified on Medline and Embase up to April 5, 2024, without language restrictions. Risk of bias was assessed with the Newcastle-Ottawa Scale, funnel plots, and Egger's tests, and meta-evidence was evaluated using NutriGrade. Findings: The baseline mean (SD) age was 50.8 years (7.2) for the NHS, 36.7 years (4.6) for the NHSII, and 53.4 years (9.6) for the HPFS. The proportion of participants of White race was 97.7% in the NHS, 96.4% in the NHSII, and 94.9% in the HPFS. Among the three cohorts, multivariable-adjusted hazard ratios [HRs (95% CIs)] for CVD, CHD, and stroke for the highest (vs. lowest) total UPF intake quintile were 1.11 (1.06-1.16), 1.16 (1.09-1.24), and 1.04 (0.96-1.12), respectively. UPF groups demonstrated divergent associations. Sugar-/artificially-sweetened drinks and processed meats were associated with higher CVD risk, whereas inverse associations were observed for bread/cold cereals, yoghurt/dairy desserts, and savoury snacks. Meta-analysing 22 prospective studies showed that total UPF intake at the highest category (vs. lowest) was associated with 17% (11%-24%), 23% (12%-34%), and 9% (3%-15%) higher CVD, CHD, and stroke risk. Meta-evidence quality was high for CHD, moderate for CVD, and low for stroke. Interpretation: Total UPF intake was adversely associated with CVD and CHD risk in US adults, corroborated by prospective studies from multiple countries, also suggesting a small excess stroke risk. Nutritional advice for cardiovascular health should consider differential consequences of group-specific UPF. Replication is needed in racially/ethnically-diverse populations. Funding: National Institutes of Health (NIH) grants supported the NHS, NHSII, and HPFS.

Transformers for Molecular Property Prediction: Lessons Learned from the Past Five Years.

Molecular Property Prediction (MPP) is vital for drug discovery, crop protection, and environmental science. Over the last decades, diverse computational techniques have been developed, from using simple physical and chemical properties and molecular fingerprints in statistical models and classical machine learning to advanced deep learning approaches. In this review, we aim to distill insights from current research on employing transformer models for MPP. We analyze the currently available models and explore key questions that arise when training and fine-tuning a transformer model for MPP. These questions encompass the choice and scale of the pretraining data, optimal architecture selections, and promising pretraining objectives. Our analysis highlights areas not yet covered in current research, inviting further exploration to enhance the field's understanding. Additionally, we address the challenges in comparing different models, emphasizing the need for standardized data splitting and robust statistical analysis.

The global burden, trends, and inequalities of individuals with developmental and intellectual disabilities attributable to iodine deficiency from 1990 to 2019 and its prediction up to 2030.

Objective: The objective of this study was to assess the global burden of disease for developmental and intellectual disabilities caused by iodine deficiency from 1990 to 2019. Methods: Using data from the global burden of disease (GBD) 2019, we conducted a cross-country inequity analysis to examine the worldwide burden of developmental and intellectual disabilities caused by the issue of iodine deficiency from 1990 to 2019. Absolute and relative inequality were assessed by the slope index of inequality and the concentration index, respectively. After summarising the latest evidence, we also projected the age-standardized prevalence and years lived with disability (YLD) rates up to 2030 using the BAPC and INLA packages in R statistical software. Results: In 2019, the global age-standardized prevalence and YLD rates for developmental and intellectual disabilities due to iodine deficiency were 22.54 per 100,000 population (95% UI 14.47 to 29.23) and 4.12 per 100,000 population (95% UI 2.25 to 6.4), respectively. From 1990 to 2019, the age-standardized prevalence and YLD rates of developmental and intellectual disabilities due to iodine deficiency decreased significantly. Geographic distribution showed that areas with lower socio-demographic indices (SDI) were the most affected. The correlation between higher SDI and lower prevalence highlights the role of economic and social factors in the prevalence of the disease. Cross-national inequity analysis shows that disparities persist despite improvements in health inequalities. In addition, projections suggest that the disease burden may decline until 2030. Conclusion: This research underscores the necessity for targeted interventions, such as enhancing iodine supplementation and nutritional education, especially in areas with lower SDI. We aim to provide a foundation for policymakers further to research effective preventative and potential alternative treatment strategies.

The systematic analysis of adults' environmental sensory tendencies dataset.

This study was conducted to investigate the profound impact of human activities on the environment, based on scientific data, recognizing the potential of environmental problems to turn into devastating crises if appropriate measures are not taken. It emphasizes the important role of education in developing environmental awareness, knowledge and sensitivity to counter adverse environmental consequences. For this purpose, a dataset was created for the emotional tendencies of university students, who represent a demographic that has the potential to influence the sustainable future of the world. A survey data including 34 different variables was collected from 388 university students in Turkey. Environmental Sensory Tendencies Dataset is intended to provide valuable guidance for the development of effective environmental education programs and policies aimed at increasing university students' awareness and participation in environmental issues. Our research underlines the vital importance of developing responsible attitudes and behaviors to effectively address environmental challenges and thereby contribute to a healthier and more sustainable global ecosystem. This study will make a significant contribution to the literature and highlight the interconnection between human actions and environmental well-being.

The long-term spatio-temporal trends in burden and attributable risk factors of major depressive disorder at global, regional and national levels during 1990-2019: a systematic analysis for GBD 2019.

AIMS: Caused by multiple risk factors, heavy burden of major depressive disorder (MDD) poses serious challenges to public health worldwide over the past 30 years. Yet the burden and attributable risk factors of MDD were not systematically known. We aimed to reveal the long-term spatio-temporal trends in the burden and attributable risk factors of MDD at global, regional and national levels during 1990-2019. METHODS: We obtained MDD and attributable risk factors data from Global Burden of Disease Study 2019. We used joinpoint regression model to assess the temporal trend in MDD burden, and age-period-cohort model to measure the effects of age, period and birth cohort on MDD incidence rate. We utilized population attributable fractions (PAFs) to estimate the specific proportions of MDD burden attributed to given risk factors. RESULTS: During 1990-2019, the global number of MDD incident cases, prevalent cases and disability-adjusted life years (DALYs) increased by 59.10%, 59.57% and 58.57%, respectively. Whereas the global age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR) and age-standardized DALYs rate (ASDR) of MDD decreased during 1990-2019. The ASIR, ASPR and ASDR in women were 1.62, 1.62 and 1.60 times as that in men in 2019, respectively. The highest age-specific incidence, prevalence and DALYs rate occurred at the age of 60-64 in women, and at the age of 75-84 in men, but the maximum increasing trends in these age-specific rates occurred at the age of 5-9. Population living during 2000-2004 had higher risk of MDD. MDD burden varied by socio-demographic index (SDI), regions and nations. In 2019, low-SDI region, Central sub-Saharan Africa and Uganda had the highest ASIR, ASPR and ASDR. The global PAFs of intimate partner violence (IPV), childhood sexual abuse (CSA) and bullying victimization (BV) were 8.43%, 5.46% and 4.86% in 2019, respectively. CONCLUSIONS: Over the past 30 years, the global ASIR, ASPR and ASDR of MDD had decreased trends, while the burden of MDD was still serious, and multiple disparities in MDD burden remarkably existed. Women, elderly and populations living during 2000-2004 and in low-SDI regions, had more severe burden of MDD. Children were more susceptible to MDD. Up to 18.75% of global MDD burden would be eliminated through early preventing against IPV, CSA and BV. Tailored strategies-and-measures in different regions and demographic groups based on findings in this studywould be urgently needed to eliminate the impacts of modifiable risk factors on MDD, and then mitigate the burden of MDD.

Global burden of young-onset gastric cancer: a systematic trend analysis of the global burden of disease study 2019.

BACKGROUND: While gastric cancer is generally declining globally, the temporal trend of young-onset (< 40 years) gastric cancer remains uncertain. We performed this analysis to determine the temporal trends of young-onset gastric cancer compared to late-onset cancer (≥ 40 years). METHODS: We extracted cross-sectional data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The burden of gastric cancer from 1990 to 2019 was assessed through indicators including incidence and mortality rates, which were classified at global, national, and regional levels, and according to socio-demographic indexes (SDI) and age or sex groups. Joinpoint regression analysis was used to identify specific years with significant changes. The correlation between AAPC with countries' average SDI was tested by Pearson's Test. RESULTS: The global incidence rate of young-onset gastric cancer decreased from 2.20 (per 100,000) in 1990 to 1.65 in 2019 (AAPC: - 0.95; 95% confidence interval [CI] - 1.25 to - 0.65; P < 0.001). Late-onset cancer incidence also decreased from 59.53 (per 100,000) in 1990 to 41.26 in 2019 (AAPC: - 1.23; 95% CI - 1.39 to - 1.06, P < 0.001). Despite an overall decreasing trend, the incidence rate of young-onset cancer demonstrated a significant increase from 2015 to 2019 (annual percentage change [APC]: 1.39; 95% CI 0.06 to 2.74; P = 0.041), whereas no upward trend was observed in late-onset cancer. Mortality rates of young- and late-onset cancer both exhibited a significant decline during this period (AAPC: - 1.82; 95% CI - 2.15 to - 1.56; P < 0.001 and AAPC: - 1.69, 95% CI - 1.79 to - 1.59; P < 0.001). The male-to-female rate ratio for incidence and mortality in both age groups have been increasing since 1990. While countries with high SDI have had a greater decline in the incidence of late-onset gastric cancer (slope of AAPC change: - 0.20, P = 0.004), it was not observed in young-onset cancer (slope of AAPC change: - 0.11, P = 0.13). CONCLUSIONS: The global incidence and mortality rates of both young- and late-onset gastric cancer have decreased since 1990. However, the incidence rate of young-onset cancer has demonstrated a small but significant upward trend since 2015. There was disparity in the decline in young-onset gastric cancer among male and high SDI countries. These findings could help to inform future strategies in preventing gastric cancer in younger individuals.

A Clinical, Pharmacological, and Formulation Evaluation of Melatonin in the Treatment of Ocular Disorders-A Systematic Review.

Melatonin's cytoprotective properties may have therapeutic implications in treating ocular diseases like glaucoma and age-related macular degeneration. Literature data suggest that melatonin could potentially protect ocular tissues by decreasing the production of free radicals and pro-inflammatory mediators. This study aims to summarize the screened articles on melatonin's clinical, pharmacological, and formulation evaluation in treating ocular disorders. The identification of relevant studies on the topic in focus was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. The studies were searched in the following databases and web search engines: Pubmed, Scopus, Science Direct, Web of Science, Reaxys, Google Scholar, Google Patents, Espacenet, and Patentscope. The search time interval was 2013-2023, with the following keywords: melatonin AND ocular OR ophthalmic AND formulation OR insert AND disease. Our key conclusion was that using melatonin-loaded nano-delivery systems enabled the improved permeation of the molecule into intraocular tissues and assured controlled release profiles. Although preclinical studies have demonstrated the efficacy of developed formulations, a considerable gap has been observed in the clinical translation of the results. To overcome this failure, revising the preclinical experimental phase might be useful by selecting endpoints close to clinical ones.

Systematic Analysis of DNA Demethylase Gene Families in Foxtail Millet (Setaria italica L.) and Their Expression Variations after Abiotic Stresses.

DNA methylation is a highly conserved epigenetic modification involved in many biological processes, including growth and development, stress response, and secondary metabolism. DNA demethylase (DNA-deMTase) genes have been identified in some plant species; however, there are no reports on the identification and analysis of DNA-deMTase genes in Foxtail millet (Setaria italica L.). In this study, seven DNA-deMTases were identified in S. italica. These DNA-deMTase genes were divided into four subfamilies (DML5, DML4, DML3, and ROS1) by phylogenetic and gene structure analysis. Further analysis shows that the physical and chemical properties of these DNA-deMTases proteins are similar, contain the typical conserved domains of ENCO3c and are located in the nucleus. Furthermore, multiple cis-acting elements were observed in DNA-deMTases, including light responsiveness, phytohormone responsiveness, stress responsiveness, and elements related to plant growth and development. The DNA-deMTase genes are expressed in all tissues detected with certain tissue specificity. Then, we investigated the abundance of DNA-deMTase transcripts under abiotic stresses (cold, drought, salt, ABA, and MeJA). The results showed that different genes of DNA-deMTases were involved in the regulation of different abiotic stresses. In total, our findings will provide a basis for the roles of DNA-deMTase in response to abiotic stress.

Person- and identity-first language in autism research: A systematic analysis of abstracts from 11 autism journals.

LAY ABSTRACT: There are many ways to refer to an individual who is on the autism spectrum. A recommended approach has been to use person-first language (PFL), such as "person with autism." A different approach is to use identity-first language (IFL), such as "autistic person." Recent studies focused on different groups of people (e.g. autistic self-advocates, parents, and practitioners) show that some groups prefer PFL (practitioners) while others prefer IFL (autistic self-advocates). However, less is known about how researchers use PFL and IFL in academic writing (e.g. studies published in scientific journals) involving autistic research participants. Our study examined 12,962 journal abstracts (short summaries of scientific articles) from 11 academic journals that publish autism research findings. We wanted to know (a) about the use of PFL and IFL across abstracts, and (b) how PFL and IFL use has changed annually over time. We examined data for all journals individually and grouped together. Our findings showed that journal abstracts generally use PFL (65%) with some using either IFL (16%) or both PFL and IFL (20%). However, journals varied, with some showing a clear majority for PFL and a couple for IFL. Examining trends over time across journals showed that while PFL appeared to be the majority for most journals, IFL has steadily increased in the recent few years. Our study helps us understand how autism researchers write about autistic individuals and offers implications for helping researchers intentionally make choices about the language used in their autism research studies.

Systematic Analysis to Identify the MIR99AHG-has-miR-21-5p-EHD1 CeRNA Regulatory Network as Potential Biomarkers in Lung Cancer.

Lung cancer (LC) remains an extremely lethal disease worldwide, and effective prognostic biomarkers are at top priority. With the rapid development of high-throughput sequencing and bioinformatic analysis methods, the quest to characterize cancer transcriptomes continues to move forward. However, the integrated systematic analysis of lncRNA-miRNA-mRNA regulatory network in LC is lacking. In this study, we collected samples of cancer tissues and adjacent normal tissues from patients with lung cancer and conducted transcriptome and small RNA sequencing to identify differentially expressed genes (DEGs), miRNAs (DEMs), and lncRNAs (DELs). The regulatory roles of miRNAs in LC were explained by functional analysis on DEM-targeted genes. The lncRNA-miRNA pairs, miRNA-mRNA pairs, and lncRNA-mRNA pairs were identified and combined to construct the interplay of lncRNA-miRNA-mRNA. We evaluated the prognostic value of selected lncRNA-miRNA-mRNA by Kaplan-Meier analysis. Finally, we analyzed the expression levels of selected DEM, DELs, and DEGs in lung cancer patients and healthy people to verify our findings. A total of 1492 DEGs, 12 DEMs, and 604 DELs were identified in LC patients. Based on the bioinformatic analysis and the regulatory mechanism of ceRNAs, 3 lncRNAs (GATA2-AS1, LINC00632, MIR99AHG), 1 miRNA (hsa-miR-21-5p) and 5 targeted genes (RECK, TIMP3, EHD1, RASGRP1 and ERG) were figured out first. Through further Kaplan-Meier analysis screening the prognostic value, we finally found the hub subnetwork (MIR99AHG-hsa-miR-21-5p-EHD1) by collating lncRNA-miRNA pairs, miRNA-mRNA pairs and lncRNA-mRNA pairs. As the key of ceRNA regulatory network, the expression of miRNA-21-5p in lung cancer patients was significantly higher than that in healthy people (P < 0.01), and its high expression was significantly associated with poor prognosis (P = 0.0025). Our study successfully constructed a MIR99AHG-hsa-miR-21-5p-EHD1 mutually regulatory network, suggesting the potential efficient biomarkers in LC.

Global evolving patterns and cross-country inequalities of inflammatory bowel disease burden from 1990 to 2019: a worldwide report.

AIMS: Inflammatory bowel disease (IBD) is a global disease. We aim to summarize the latest epidemiological patterns of IBD at the national, regional and global levels to give well-deserved attention and outline facilitating measures to reduce the disease burden. METHODS: We collected the incidence, prevalence, mortality and disability-adjusted life years (DALYs) of IBD in 204 countries and territories from 1990 to 2019 using data from the Global Burden of Disease Study 2019. We further calculated the estimated annual percentage change (EAPC) to qualify the temporal trends of IBD burden by sex, age and region over the past 30 years. RESULTS: Globally, a total of 404.55 thousand incident cases, 4898.56 thousand prevalent cases, 41.00 thousand deaths and 1622.50 thousand DALYs of IBD were estimated in 2019. The age-standardized DALYs decreased from 27.2 in 1990 to 20.15 per 100,000 people in 2019, with an EAPC of -1.04. The high socio-demographic index regions presented pronounced age-standardized rates (ASRs) consistently over the last 30 years. The high-income North America had the highest ASRs in 2019, followed by Western Europe and Australasia. No gender difference was observed after being stratified by sex. CONCLUSIONS: The accumulated IBD patients are expected to increase in the future due to the increased rate of IBD in developing countries, and social aging in developed countries. Understanding the changes in epidemiological patterns helps to provide evidence to mitigate the rising burden of IBD.

Global, Regional, and National Burden of Myocarditis in 204 Countries and Territories From 1990 to 2019: Updated Systematic Analysis.

BACKGROUND: Myocarditis is characterized by high disability and mortality, and imposes a severe burden on population health globally. However, the latest global magnitude and secular trend of myocarditis burden have not been reported. OBJECTIVE: This study aimed to delineate the epidemiological characteristics of myocarditis burden globally for optimizing targeted prevention and research. METHODS: Based on the Global Burden of Disease Study 2019, the myocarditis burden from 1990 to 2019 was modeled using the Cause of Death Ensemble tool, DisMod-MR, and spatiotemporal Gaussian regression. We depicted the epidemiology and trends of myocarditis by sex, age, year, region, and sociodemographic index (SDI). R program version 4.2.1 (R Project for Statistical Computing) was applied for all statistical analyses, and a 2-sided P-value of <.05 was considered statistically significant. RESULTS: The number of incident cases (1,268,000) and deaths (32,450) associated with myocarditis in 2019 increased by over 1.6 times compared with the values in 1990 globally. On the other hand, the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) decreased slightly from 1990 to 2019. The disability-adjusted life years (DALYs) decreased slightly in the past 3 decades, while the age-standardized DALY rate (ASDR) decreased greatly from 18.29 per 100,000 person-years in 1990 to 12.81 per 100,000 person-years in 2019. High SDI regions always showed a more significant ASIR. The ASIR slightly decreased in all SDI regions between 1990 and 2019. Middle SDI regions had the highest ASMR and ASDR in 2019. Low SDI regions had the lowest ASMR and ASDR in 2019. The age-standardized rates (ASRs) of myocarditis were higher among males than among females from 1990 to 2019 globally. All ASRs among both sexes had a downward trend, except for the ASMR among males, which showed a stable trend, and females had a more significant decrease in the ASDR than males. Senior citizens had high incident cases and deaths among both sexes in 2019. The peak numbers of DALYs for both sexes were noted in the under 1 age group in 2019. At the national level, the estimated annual percentage changes in the ASRs had significant negative correlations with the baseline ASRs in 1990. CONCLUSIONS: Globally, the number of incident cases and deaths associated with myocarditis have increased significantly. On the other hand, the ASRs of myocarditis showed decreasing trends from 1990 to 2019. Males consistently showed higher ASRs of myocarditis than females from 1990 to 2019 globally. Senior citizens gradually predominated in terms of myocarditis burden. Policymakers should establish targeted control strategies based on gender, region, age, and SDI; strengthen aging-related health research; and take notice of the changes in the epidemic characteristics of myocarditis.

Brachytherapy is an effective and safe salvage option for re-irradiation in recurrent glioblastoma (rGBM): A systematic review.

PURPOSE: To evaluate the clinical efficacy and toxicity of brachytherapy as a salvage therapy for patients with recurrent glioblastoma (rGBM). METHODS AND MATERIALS: We searched the PubMed, Embase, and Cochrane libraries from its inception to June 2023, for eligible studies in which patients underwent brachytherapy for rGBM. Outcomes of interest were mOS, mPFS, OS, PFS, and adverse events (AEs). For individual clinical survival outcomes and common AEs, weighted-mean descriptive statistics were calculated as a summary measure using study sample size as the weight. The calculation formula is as follows: weighted-mean = Σwx/Σw (w is the sample size and x is the outcome). RESULTS: This review included 29 studies with a total of 1202 rGBM patients, including 22 retrospective and 7 prospective studies. The results showed that from the time of brachytherapy, the mOS and mPFS were 6.8 to 24.4 months and 3.7 to 11.7 months. The OS of 6 months, 1 year, 18 months, 2 years, and 3 years after brachytherapy were 58.3 % to 85.2 % (weighted-mean 76.2 %), 26 % to 66 % (weighted-mean 41.9 %), 20 % to 37 % (weighted-mean 27.6 %), 11 % to 23 % (weighted-mean 14.8 %), and 8 % to 15 % (weighted-mean 12.1 %), respectively. The PFS of 6 months and 1 year after brachytherapy were 26.7 % to 86 % (weighted-mean 53.4 %) and 14 % to 81 % (weighted-mean 24.1 %). Most patients with rGBM will experience treatment failure again during the follow-up period, mainly local (10.7 % to 79.4 %) or marginal(3.6 % to 22.2 %) recurrence, followed by distant failure (6.7 % to 57.7 %). Although therapeutic AEs had not been uniformly reported, the overall toxicity rate was considered to be low. The common AEs reported included progressive neurologic deterioration, seizures, CSF leak, brain necrosis, hemorrhage, and infection/meningitis, with a weighted-mean incidence of 1.9 %, 2.4 %, 4.1 %, 5.4 %, 2.1 %, and 3.8 %, respectively. CONCLUSIONS: The evidence summarized above, albeit mostly level III, suggests that brachytherapy has acceptable safety and good post-treatment clinical efficacy for selected patients with rGBM. Well-designed, high-quality, large-sample randomized controlled and prospective studies are needed to further validate these findings.

Assessment of variables determining the health management departments' efficiency with analytical hierarchy process.

This study was conducted to determine the variables that play a role in the efficiency of Health Management departments in Turkey and the ranking of them in order of importance. These variables were determined by systematic analysis. The Prisma method was used in the systematic analysis approach. Input and output variables used in studies assessing the efficiency of higher education institutions in the literature were listed. The ranking of these variables was determined by Analytical Hierarchy Process (AHP) method. The questionnaire used for the AHP analysis and the judgments of 127 academicians working in Health Management Departments in universities in Turkey were assessed. The first three input variables found as a result of the AHP were "the number of registered undergraduate students per faculty member", "the number of faculty members", and "the number of other academic staff". The most important three output variables included "the number of articles searched on SCI, SSCI, SCI-E", "the number of papers presented in international congresses", and "the count of publications published in international peer-reviewed journals". To achieve positive developments in the efficiency of Health Management Departments, it is recommended to carry out studies to increase the number of qualified publications.

Comparison of the Effectiveness of Prolonged Infusion and Intermittent Infusion of Meropenem in Patients With Sepsis: A Meta-Analysis.

The aim of this study was to compare the clinical effectiveness of prolonged infusion and intermittent infusion of meropenem in patients with sepsis. This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. PubMed, Web of Science, Scopus, and the Cochrane Library were searched without any language or time restrictions, up to September 25, 2023. The primary outcomes assessed in this meta-analysis included clinical success and all-cause mortality. Other outcomes assessed in this study encompassed the mean length of ICU stay. Total eight studies met the eligibility criteria and were included in this meta-analysis. Pooled analysis showed that the clinical success rate was significantly higher in patients receiving prolonged infusion of meropenem compared to intermittent infusion (RR: 1.49, 95% CI: 1.30 to 1.70). All-cause mortality was 24% significantly lower in patients receiving prolonged infusion of meropenem compared to intermittent infusion (RR: 0.76, 95% CI: 0.60 to 0.96). The results suggest that prolonged infusion of meropenem could be a more effective and efficient treatment for sepsis patients. However, more randomized controlled trials are needed to confirm these findings and to establish the optimal dosing and administration schedule for prolonged infusion of meropenem.

An economic evaluation of pit and fissure sealants and fluoride varnishes in preventing dental caries: a systematic review.

The aim was to systematically evaluate the cost-effectiveness of pit and fissure sealants (PFSs) compared with that of fluoride varnishes (FVs) in dental caries prevention. We searched four electronic databases including the Cochrane Oral Health Group's Trials Register (till 03 June 2022), Web of Science (from 1945 to 03 June 2022), PubMed (from 1996 to 03 June 2022), and EMBASE via Ovid (from 1980 to 03 June 2022) to identify the cost and effectiveness of PFSs and FVs in decreasing dental caries incidence. Two researchers independently screened search results, extracted data from the included studies, and conducted the risk of bias assessments. The main characteristics of the included studies were extracted and analyzed. The initial search produced 874 articles. After removing duplicates and full-text review, 19 studies were included. In this study: nine studies were on PFSs comparison with control; five on PFSs comparison with FVs; and five on FVs comparison with control. Regarding the type of economic evaluation (EE), 13 studies conducted cost-effectiveness analysis, five conducted cost-utility analyses, and one conducted both cost-effectiveness analysis and cost-utility analyses. The cost-effectiveness evaluation of PFSs and FVs in the available studies was limited. The prevalence of dental caries, payers' willingness to pay, length of follow-ups, delivery settings, retention rate of PFS, and application intervals of FV can affect the economic evaluation of these two methods for dental caries prevention. Therefore, more studies in the future are need to draw clear conclusions about which method is more cost-effective for the two preventive interventions in future.

Single-cell landscape analysis reveals systematic senescence in mammalian Down syndrome.

BACKGROUND: Down syndrome (DS), which is characterized by various malfunctions, is the most common chromosomal disorder. As the DS population continues to grow and most of those with DS live beyond puberty, early-onset health problems have become apparent. However, the cellular landscape and molecular alterations have not been thoroughly studied. METHODS: This study utilized single-cell resolution techniques to examine DS in humans and mice, spanning seven distinct organs. A total of 71 934 mouse and 98 207 human cells were analyzed to uncover the molecular alterations occurring in different cell types and organs related to DS, specifically starting from the fetal stage. Additionally, SA-ß-Gal staining, western blot, and histological study were employed to verify the alterations. RESULTS: In this study, we firstly established the transcriptomic profile of the mammalian DS, deciphering the cellular map and molecular mechanism. Our analysis indicated that DS cells across various types and organs experienced senescence stresses from as early as the fetal stage. This was marked by elevated SA-ß-Gal activity, overexpression of cell cycle inhibitors, augmented inflammatory responses, and a loss of cellular identity. Furthermore, we found evidence of mitochondrial disturbance, an increase in ribosomal protein transcription, and heightened apoptosis in fetal DS cells. This investigation also unearthed a regulatory network driven by an HSA21 gene, which leads to genome-wide expression changes. CONCLUSION: The findings from this study offer significant insights into the molecular alterations that occur in DS, shedding light on the pathological processes underlying this disorder. These results can potentially guide future research and treatment development for DS.

Anticancer mechanisms on pyroptosis induced by Oridonin: New potential targeted therapeutic strategies.

Pyroptosis is a type of inflammatory cell death that is triggered by the formation of pores on the cell membrane by gasdermin (GSDM) family proteins. This process activates inflammasomes and leads to the maturation and release of proinflammatory cytokines such as interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). Pyroptosis, a form of programmed cell death, has been found to be associated with various biomolecules such as caspases, granzymes, non-coding RNA (lncRNA), reactive oxygen species (ROS), and NOD-like receptor protein 3 (NLRP3). These biomolecules have been shown to play a dual role in cancer by affecting cell proliferation, metastasis, and the tumor microenvironment (TME), resulting in both tumor promotion and anti-tumor effects. Recent studies have found that Oridonin (Ori) has anti-tumor effects by regulating pyroptosis through various pathways. Ori can inhibit pyroptosis by inhibiting caspase-1, which is responsible for activating pyroptosis of the canonical pathway. Additionally, Ori can inhibit pyroptosis by inhibiting NLRP3, which is responsible for activating pyroptosis of the noncanonical pathway. Interestingly, Ori can also activate pyroptosis by activating caspase-3 and caspase-8, which are responsible for activating pyroptosis of the emerging pathway; Ori has been found to be effective in inhibiting pyroptosis by blocking the action of perforin, which is responsible for facilitating the entry of granzyme into cells and activating pyroptosis. Additionally, Ori plays a crucial role in regulating pyroptosis by promoting the accumulation of ROS while inhibiting the ncRNA and NLRP3 pathways. It is worth noting that all of these pathways ultimately regulate pyroptosis by influencing the cleavage of GSDM, which is a key factor in the process. These studies concludes that Ori has extensive anti-cancer effects that are related to its potential regulatory function on pyroptosis. The paper summarizes several potential ways in which Ori participates in the regulation of pyroptosis, providing a reference for further study on the relationship between Ori, pyroptosis, and cancer.

Integrated analysis reveals the protective mechanism and therapeutic potential of hyperbaric oxygen against pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a dreadful, chronic, and irreversibly progressive disease leading to death with few effective treatments. Our previous study suggested that repetitive hyperbaric oxygen (HBO) treatment alleviates bleomycin-induced pulmonary fibrosis in mice. Here, we investigated the protective mechanism of HBO treatment against pulmonary fibrosis using an integrated approach. Analyzing publicly available expression data from the mouse model of bleomycin-induced pulmonary fibrosis as well as IPF patients, several potential mechanisms of relevance to IPF pathology were identified, including increased epithelial-to-mesenchymal transition (EMT) and glycolysis. High EMT or glycolysis scores in bronchoalveolar lavage (BAL) were strong independent predictors of mortality in multivariate analysis. These processes were potentially driven by hypoxia and blocked by HBO treatment. Together, these data support HBO treatment as a viable strategy against pulmonary fibrosis.

Systematic Analysis of Genes Related to Selenium Bioaccumulation in Microalgae: A Review.

Se is one of the essential nutrients for human health and animal growth; it participates in various physiological functions, such as antioxidant and immune response and metabolism. Se deficiency is related in the animal industry to poor production performance and the appearance of health problems in humans. Therefore, interest has arisen in producing fortified foods, nutritional supplements, and animal feed products enriched with Se. A sustainable strategy for bio-based products enriched with Se is microalgae. These are characterized by the ability to bioaccumulate inorganic Se and metabolize it into organic Se for product formulations of industrial interest. Although there are some reports on Se bioaccumulation, further exploration is needed to understand the effects of Se bioaccumulation in microalgae. Therefore, this article presents a systematic review of the genes or groups of genes that trigger biological responses associated with the metabolization of Se in microalgae. A total of 54,541 genes related to Se metabolization distributed in 160 different classes were found. Similarly, trends were identified through bibliometric networks on strains of greatest interest, bioproducts, and scientific production.