Search Results (606)

Background: CCAAT/enhancer-binding protein alpha–basic leucine zipper in-frame (CEBPA^bZIP-inf) mutations are associated with favorable outcomes in acute myeloid leukemia (AML). So far, there are limited data on integrating clinical and genomic features impacting the outcomes. Methods: Clinical and genomic data from consecutive patients with CEBPA^bZIP-inf were reviewed. A Cox proportional hazards regression was used to identify the variables associated with event-free survival (EFS), relapse-free survival (RFS) and survival. Results: 224 CEBPA^bZIP-inf patients were included in this study. In the 201 patients, except for the 19 receiving the transplant in the first complete remission with no events (the transplant cohort), multivariate analyses showed that IKZF1 mutations/deletions were significantly associated with poor EFS (p = 0.001) and RFS (p < 0.001); FLT3-ITD mutations, poor RFS (p = 0.048). In addition, increasing WBC count, lower hemoglobin concentration, non-intensive induction, and MRD positivity after first consolidation predicted poor outcomes. On the basis of the number of adverse prognostic covariates for RFS, the 201 patients were classified into low-, intermediate- or high-risk subgroups, and there were significant differences in the 3-year EFS, RFS and survival rates (all p < 0.001); however, except for survival in the low-risk group, these metrics were lower than those in the transplant cohort. Conclusions: We identified a potential high-risk population with adverse prognostic factors in CEBPA^bZIP-inf AML patients for which transplantation should be considered. Full article

Vegetables and fruits grown in urban areas pose a potential threat to human health due to contamination with heavy metals (HMs). This study aimed to identify and quantify the concentrations of heavy metals (Fe, Mn, Zn, Cu, Pb, Cd) in tomatoes, leafy vegetables, and fruits collected from 16 allotment gardens (AGs) located in Warsaw. A total of 112 samples were analyzed (72 vegetable and 40 fruit samples). Vegetables from AGs accumulated significantly higher levels of HMs than fruits. Leafy vegetables, particularly those cultivated near high-traffic roads, exhibited markedly elevated levels of Pb, Cd, and Zn compared to those grown in peripheral areas. Lead concentrations exceeded permissible limits by six to twelve times, cadmium by one to thirteen times, and zinc by 0.7 to 2.4 times. Due to high levels of Pb and Cd, tomatoes should not be cultivated in urban environments. Regardless of location, only trace amounts of HMs were detected in fruits. The greatest health risk is associated with the consumption of leafy vegetables. Lettuce should be considered an indicator plant for assessing environmental contamination. The obtained Hazard Index (HI) values indicate that only the tested fruits are safe for consumption. Meanwhile, the values of the Hazard Quotient (HQ) indicate no health risk associated with the consumption of lettuce, cherries, and red currants. Among the analyzed elements, Pb showed a higher potential health risk than other metals. This study emphasizes the need for continuous monitoring of HM levels in urban soils and the establishment of baseline values for public health purposes. Remediation of contaminated soils and the implementation of safer agricultural practices are recommended to reduce the exposure of urban populations to the risks associated with the consumption of contaminated produce. In addition, the safety of fruits and vegetables grown in urban areas is influenced by the location of the AGs and the level of industrialization of the agglomeration. Therefore, the safety assessment of plant products derived from AGs should be monitored on a continuous basis, especially in vegetables. Full article

Background/Objectives: Albumin supplementation is widely used for hypoalbuminemia treatment in patients with critical illness, especially those with cirrhosis. However, studies have demonstrated that routine albumin administration is not always advantageous. We examined how albumin supplementation affects survival outcomes in patients with sepsis with hypoalbuminemia. Methods: This study was conducted by researchers in Taiwan using data from the TriNetX research platform, covering the period from 1 April 2014 to 30 April 2024. This platform aggregates real-world data from healthcare organizations worldwide. From this dataset, 1,147,433 patients who developed sepsis and hypoalbuminemia with albumin levels <3.5 g/dL were identified. The study population was stratified into two groups on the basis of whether they received albumin infusion or not. To compare outcomes, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated between propensity-score-matched patients who did and did not receive albumin supplementation. Subgroup analysis by albumin levels was conducted. Results: Albumin infusion was linked to increased risks of 30-day mortality (HR [95% CI] = 1.800 [1.774–1.827], p < 0.05), shock (HR [95% CI] = 1.436 [1.409–1.465], p < 0.05), septic shock (HR [95% CI] = 1.384 [1.355–1.415], p < 0.05), hypovolemic shock (HR [95% CI] = 1.496 [1.391–1.608], p < 0.05), cardiogenic shock (HR [95% CI] = 1.553 [1.473–1.637], p < 0.05), heart failure (HR [95% CI] = 1.098 [1.080–1.116], p < 0.05), and pulmonary edema (HR [95% CI] = 1.479 [1.438–1.520], p < 0.05). The subgroup analysis by albumin levels revealed a trend of increased mortality risk with albumin supplementation in patients with high baseline albumin levels. Conclusions: Patients with sepsis with hypoalbuminemia who received albumin supplementation exhibited high 30-day mortality rates and increased risks of shock, heart failure, and pulmonary edema compared with those who did not. These findings indicate that routine albumin administration may be linked with unfavorable outcomes in these patients. Full article

The coronavirus disease 2019 (COVID-19) pandemic has led to substantial health and financial burdens worldwide, and vaccines provide hope for reducing the burden of this pandemic. However, vaccinated people remain at risk for SARS-CoV-2 infection. Genome-wide association studies (GWASs) may identify potential genetic factors involved in the development of COVID-19 breakthrough infections (BIs); however, very few or no GWASs have been conducted for COVID-19 BI thus far. We conducted a GWAS and detailed bioinformatics analysis on COVID-19 BIs in a European population via the UK Biobank (UKBB). We conducted a series of analyses at different levels, including SNP-based, gene-based, pathway, and transcriptome-wide association analyses, to investigate genetic factors associated with COVID-19 BIs and hospitalized infections. The polygenic risk score (PRS) and Hoeffding’s test were performed to reveal the genetic relationships between BIs and other medical conditions. Two independent loci (LD-clumped at r² = 0.01) reached genome-wide significance (p < 5 × 10⁻⁸), including rs36170929, which mapped to LOC102725191/VWDE, and rs28645263, which mapped to RETREG1. A pathway enrichment analysis highlighted pathways such as viral myocarditis, Rho-selective guanine exchange factor AKAP13 signaling, and lipid metabolism. The PRS analyses revealed significant genetic overlap between COVID-19 BIs and heart failure and between HbA1c and type 1 diabetes. Genetic dependence was also observed between COVID-19 BIs and asthma, lung abnormalities, schizophrenia, and type 1 diabetes on the basis of Hoeffding’s test. This GWAS revealed two significant loci that may be associated with COVID-19 BIs and a number of genes and pathways that may be involved in BIs. Genetic overlap with other diseases was identified. Further studies are warranted to replicate these findings and elucidate the mechanisms involved. Full article

Background/Objectives: Endocrine hormones play critical roles in regulating physiological processes, and previous studies have reported their associations with psychiatric disorders. Levels of endocrine hormones and the risk of developing psychiatric disorders are influenced by both genetic and non-genetic factors. However, the shared genetic basis underlying these associations remains largely unexplored. This study aims to dually evaluate the genetic correlations among endocrine hormones, including thyroid and sex hormones, as well as between endocrine hormone metrics and psychiatric disorders to identify potential shared genetic architectures. Methods: We obtained genome-wide association study summary statistics for six thyroid hormone metrics, three sex hormone metrics, and ten psychiatric disorders from predominantly European-ancestry populations. Genetic correlations were computed using linkage disequilibrium score regression after harmonizing variant data to ensure consistency across studies. Results: Significant genetic correlations were observed among thyroid and sex hormone metrics, indicating a strong shared genetic basis. Sex hormones exhibited multiple genetic correlations with psychiatric disorders, including negative correlations between sex hormone-binding globulin and attention-deficit hyperactivity disorder (ADHD) (p = 3.95 × 10⁻¹²) and major depressive disorder (p = 4.67 × 10⁻⁵), and positive genetic correlations with anorexia nervosa (p = 2.86 × 10⁻¹²) and schizophrenia (p = 2.00 × 10⁻⁴). Testosterone and estradiol had negative genetic correlations with ADHD and major depressive disorder, while testosterone had positive genetic correlations with anorexia nervosa and schizophrenia. Although thyroid hormone metrics did not exhibit Bonferroni-significant genetic correlations, nominal associations were observed, such as a negative genetic correlation between thyroid-stimulating hormone and major depressive disorder (p = 2.33 × 10⁻²). Conclusions: These findings suggest a shared genetic basis between endocrine hormones and psychiatric disorders, particularly for sex hormones. Future studies leveraging larger, more diverse populations are warranted to validate and extend the genetic correlations observed in this study. Full article

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition with a complex and multifactorial etiology, diagnosed on the basis of clinical criteria. Medical comorbidities are common and often lead to instrumental examinations; however, the clinical utility of routinely performing such tests remains uncertain. This study aimed to assess the practical value of instrumental assessments in ASD by examining both prescribing behaviors and the prevalence of abnormal findings in a sample of autistic children. Methods: A combined-method approach was adopted: (1) an online survey of child neuropsychiatrists across the Piedmont region (Italy) explored current attitudes and practices regarding instrumental testing in children with ASD; (2) a retrospective cross-sectional analysis examined the frequency and clinical relevance of abnormal findings in ASD patients who underwent comprehensive testing at a tertiary hospital in Turin. Results: The survey showed that 85.7% of centers follow specific protocols for instrumental examinations, though practices vary considerably. Genetic testing and blood analyses are routinely performed, while EEG, MRI, audiometry, and metabolic screenings are generally based on clinical indication. In the retrospective study, instrumental tests revealed a low rate of clinically significant findings. Clinically relevant genetic abnormalities were detected in 7.9% of CGH-array tests. EEG abnormalities were seen in 9% of cases, though 57% had nonspecific or unclear results. Among biochemical parameters, notable findings included altered lipid profiles (45%), ferritin deficiency (24%), and anemia (12.5%) and no metabolic disorders were identified. Discussion: These findings highlight substantial variability in clinical practice and suggest that while some instrumental tests may provide valuable insights, routine screening is often of limited benefit. The high prevalence of nonspecific findings reinforces the need for careful clinical correlation, emphasizing the importance of balancing comprehensive assessment against the risks of over-testing and challenges in interpreting results. Future research should focus on developing evidence-based guidelines for instrumental assessments in this population. Full article

To develop interventions and policies to promote healthy and sustainable diets during times of crisis, it is important to understand how populations respond to such situations based on real-life examples. Using the recent COVID-19 pandemic as a case study to identify risk and protective factors for such situations, we implemented the first longitudinal mixed-methods approach of this topic to date. Data were collected from a sample of UK parents (stratified for gender and socioeconomic status) through two surveys and a set of focus groups during the pandemic. The focus groups identified multifaceted drivers of change linked to capability (e.g., shielding), opportunity (e.g., time, food access and availability), and motivation (e.g., reflective motivation, stress and mental health challenges) barriers. High levels of COVID-19 stress were linked with less healthy and sustainable diets in the survey results, while higher social cohesion, reflective motivation to consume healthy foods, and positive coping scores were protective, and linked to healthier and more sustainable diets. A range of coping strategies were identified, including home cooking and meal planning, which could provide a basis for future intervention development to reduce stress, maintain wellbeing, and improve dietary outcomes in future crisis situations. Full article

Objectives—Health screening data were collected from participants at Native American community and celebratory events to evaluate their health status and identify common health concerns. These results will form the basis for developing community-based health care interventions to address health inequalities. Design—A descriptive, observational design was used to gather data in line with STROBE guidelines. Results—The screening data revealed that this population was largely obese, had low bone mass, and were in various states of dehydration. These characteristics can lead to major health risks and morbidities including diabetes, hypertension, cancer, hormone and neurotransmitter imbalances, bone fractures, and psychological disorders such as depression and anxiety. Conclusions—Professional and community efforts are essential to meet the health care needs of this population and avoid the repercussions of obesity, low bone mass, and dehydration. By incorporating collaborative input from the Native American community, we intend to develop partnerships for goals of promoting effective, culturally appropriate interventions to meet these health inequalities and promote good health and well-being. Full article

Youth make up a fifth of the world’s population and will suffer the consequences of the climate catastrophe to differing extents depending on their social and geographical locations. The climate crisis is thus a matter of both intergenerational and racial/imperial injustice. Intersectional and interdisciplinary climate justice approaches are growing in the field of youth climate activism and, more often, these are necessarily engaging with collaborative methods to platform the voices of marginalised youth and those who live the colonial difference. Our paper provides early reflections from a youth climate activism artistic research project titled ‘Theatre of Climate Action: Amplifying Youth Voices for Climate Justice in Guadeloupe and South Africa’ (ToCA). In this project, sixteen young people aged 18-30 from South Africa and Guadeloupe collaborate to design, produce, and create theatre performances that reflect their exploration of climate justice through their lived experiences using artistic research methods. Specifically, we examine the opportunities and challenges in using the framework of Safe(r), Brave(r), and Riskier Spaces to support collaborative and emancipatory art-making practices that allow youth to become co-creators in this project. Insights revealed that an intentional embrace of safety, bravery, and risk as an ethico-political basis for art making was critical to cultivate a sense of community, trust, and belonging for youth co-creators. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1–3% of the population globally. Owing to its multifactorial origin, complex genetics, and heterogeneity in clinical phenotypes, it is difficult to faithfully model ASD. In essence, ASD is an umbrella term for a group of individually rare disorders, each risk gene accounting for <1% of cases, threaded by a set of overlapping behavioral or molecular phenotypes. Validated behavioral tests are considered a gold standard for ASD diagnosis, and several animal models (rodents, pigs, and non-human primates) have traditionally been used to study its molecular basis. These models recapitulate the human phenotype to a varying degree and have been indispensable to preclinical research, but they cannot be used to study human-specific features such as protracted neuronal maturation and cell-intrinsic attributes, posing serious limitations to translatability. Human stem cell-based models, both as monolayer 2D cultures and 3D organoids and assembloids, can circumvent these limitations. Generated from a patient’s own reprogrammed cells, these can be used for testing therapeutic interventions that are more condition and patient relevant, targeting developmental windows where the intervention would be most effective. We discuss some of these advancements by comparing traditional and recent models of ASD. Full article

Landslides in Ecuador are one of the most common deadly events in natural hazards, such as the one on 26 March 2023. A large-scale landslide occurred in Alausí, Chimborazo province, causing 65 fatalities and 10 people to disappear, significant infrastructural damage, and the destruction of six neighborhoods. This study presents a detailed case analysis of the anthropogenic factors that could have contributed to the instability of the affected area. Field investigations and a review of historical, geological, and social information are the basis for analyzing the complex interactions between natural and human-induced conditions. Key anthropogenic contributors identified include unplanned urban expansion, ineffective drainage systems, deforestation, road construction without adequate geotechnical support, and changes in land use, particularly agricultural irrigation and wastewater disposal. These factors increased the area’s susceptibility to slope failure, which, combined with intense rainfall and past seismic activity, could have caused the rupture process’s acceleration. The study also emphasizes integrating geological, hydrological, and urban planning assessments to mitigate landslide risks in geologically sensitive regions such as Alausí canton. The findings conclude that human activity could be an acceleration factor in natural processes, and the pressure of urbanization amplifies the consequences. This research underscores the importance of sustainable land management, improved drainage infrastructure, and land-use planning in hazard-prone areas. The lessons learned from Alausí can inform risk reduction strategies across other mountainous and densely populated regions worldwide, like the Andean countries, which have similar social and environmental conditions to Ecuador. Full article

With the nationwide completion of China’s large-scale Poverty Alleviation Relocation (PAR) initiative in 2020, the government’s poverty alleviation efforts have officially entered the “post-poverty era”. However, many regions still lack well-established sustainable development mechanisms and face a potential risk of returning to poverty. To better stabilize the achievements of poverty alleviation, this study examines the potential risk of returning to poverty after the first Five-Year Transition Period (2021–2025) from a livelihood space perspective and proposes optimization directions for PAR policies in future poverty reduction efforts. Research findings indicate that simply altering geographical conditions is insufficient to achieve stable poverty alleviation. The production space of relocated populations is vulnerable to the stability and precision in resource supply, which may lead to recurring poverty due to policy discontinuities and administrative preferences. Meanwhile, improvements in living spaces are constrained by imbalances in household income and expenditure. This study also found that, on the one hand, changes in residential patterns break the original boundaries of administrative villages by incorporating migrants from different villages into concentrated communities, leading to the expansion of weak-tie networks while, on the other hand, the relocation process disrupts some of the migrants’ original strong-tie networks, and the concentration and clustering of impoverished groups in relocation communities further lead to the contraction of these networks. Additionally, the unique characteristics of relocation communities generate exorbitant governance costs and population management difficulties that far exceed the service provision and administrative capacities of community organizations. In the long run, this situation proves detrimental to normalized community governance and dynamic poverty relapse monitoring and interventions. Accordingly, this study proposes relevant policy recommendations from the following four aspects, i.e., strengthening endogenous development capacity, improving social security mechanisms, expanding social support networks, and enhancing organizational governance capabilities, aiming to provide both a theoretical basis and a decision-making reference for future poverty alleviation efforts. Full article

Background/Objectives: The clinical utility of reproductive carrier screening varies based on the genes tested, variant reporting policies, and the screened patient population. This study aims to evaluate the outcomes of carrier screening among reproductive couples undergoing testing in a routine clinical setting. Methods: A total of 1595 couples, primarily referred by reproductive endocrinology and infertility specialists, underwent couple-based carrier screening across 390 genes. Carrier states were assessed on a couple basis and reported only if a couple were at risk of having affected offspring. At-risk conditions were classified by severity, as well as their likelihood of clinical impact based on the specific variants detected in each at-risk couple. Secondary findings with potential personal utility were also evaluated. Results: Among the screened couples, 4.2% were at risk of having a child with a genetic condition. When limited to high-clinical-impact results, the at-risk couple rate decreased to 1.0%, with 44% of these cases involving CFTR, SMN1, or FMR1. Secondary findings were identified in 1.7% of individuals. Conclusions: Carrier screening for only CFTR, SMN1, and FMR1 will miss more than half of at-risk couples, underscoring the importance of broader carrier screening. Specific variants and their combinations can influence the predicted clinical impact of at-risk conditions, marking a key advantage of couple-based reporting. Secondary findings were common, highlighting the importance of discussing these potential findings during pre-test counselling. Full article

Niacin therapy has been a mainstay in traditional secondary prevention of stroke. Supplemental use of niacin has been used to improve lipid panel markers, including lowering low-density lipoproteins and triglycerides, and raising high-density lipoproteins, which have been associated with lower risk for stroke. This supplementation has been supported by earlier studies regarding niacin and its role in reducing cardiovascular risk. However, recent studies have called into question the efficacy of niacin therapy and some studies even show negative effects that are associated with taking supplemental niacin. In the present investigation, review of niacin-mediated benefits to cardiovascular disease and newer research suggesting that niacin may be ineffective with the potential of adverse side effects are summarized. This review further highlights the need for more population-level studies regarding the effects of supplemental niacin use to provide a scientific basis for its therapeutic role in cardiovascular disease, including improvement in lipid panel markers and stroke prevention. Full article

Efanesoctocog alfa (Altuvoct; BIVV001) is a fusion protein comprising domains of (i) factor VIII, (ii) the von Willebrand factor, and (iii) IgG1 coupled to two polypeptide linkers. The half-life of efanesoctocog alfa in plasma is about 40 h. The polypeptide linkers are released by thrombin activation, resulting in an active form of efanesoctocog alfa that results in the formation of a fibrin clot. Data from two single-arm ongoing studies were submitted: the XTEND-1 study enrolled 159 subjects aged 12–72 years, and the XTEND-kids study enrolled 74 subjects aged <12 years; all subjects had severe haemophilia A. Single-arm studies are not amenable to conventional statistical analysis of ‘effect of cause’, and so a supplementary analysis was conducted on the basis of ‘cause of effect’, making use of the scheme described by Toulmin coupled to an analysis of causal inference. Overall, the claim that Altuvoct is indicated to treat people aged ≥2 years with severe (and moderate) haemophilia A was considered to be supported by the results of the submitted studies and associated modelling exercises; the benefit–risk evaluation of Altuvoct was found to be positive in the target population. Full article