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Interest in HIV pre-exposure prophylaxis use and associated factors among people who inject drugs in Iran: a nationwide survey in 2023
Abstract Despite the effectiveness of pre-exposure prophylaxis (PrEP) in reducing HIV incidence, this intervention is inaccessible in Iran. We examined the interest in using PrEP and associated factors among people who inject drugs (PWID) in 2023 using data from 2,174 PWID. The main outcome was interest in using PrEP, which was divided into three categories: interest in using PrEP under any circumstances, interest in using PrEP if provided for free, and no interest in using PrEP. We found that 37.9% of PWID were interested in using PrEP under any circumstances, 48.3% were interested in using PrEP if provided for free, and 13.8% were not interested in using PrEP. Additionally, only 7.7% of participants reported prior awareness of PrEP. Having high school or more education (adjusted relative risk ratios [ARRR]: 1.92; 95% confidence interval [CI]: 1.42, 2.61), having access to opioid agonist treatment (OAT) in the last six months (ARRR: 1.59; 1.13, 2.25), and having sufficient HIV knowledge (ARRR: 2.87; 2.03, 4.06) were positively associated with interest in using PrEP under any circumstances. Similarly, having high school or more education (ARRR: 1.50; 1.10, 2.04), having access to OAT in the last six months (ARRR: 2.63; 1.88, 3.67), and having sufficient HIV knowledge (ARRR: 4.53; 3.23, 6.37) were associated with interest in using PrEP if provided for free. Health insurance was negatively associated with interest in using PrEP under any circumstances (ARRR: 0.64; 0.47, 0.87) and with interest in using PrEP if provided for free (ARRR: 0.33; 0.23, 0.45). The findings show a strong potential for PrEP acceptance, indicating that addressing financial and logistical barriers to free PrEP access could greatly reduce HIV incidence among PWID in Iran.
Evaluation of seismic behavior and collapse capacity of dual RC frame–shear wall structures considering soil-structure interaction under varying soil conditions
Swarm-based intelligent models for developing cybersecurity frameworks with IDS
Climate adaptation policies in Central Asia overlook mental health
PERK/ATF4/LAMP3-arm contributes to the aggressive phenotype of hepatocellular carcinoma cells in response to the chronic ethanol exposure
Quantum kernel methods for marketing analytics with convergence theory and separation bounds
Probabilistic risk assessment of occupational exposure to respirable crystalline silica among ceramic workers in an industrial town in Iran: a Monte Carlo simulation approach
Enhancing salinity tolerance and growth of Spinacia oleracea L. using halophilic plant growth-promoting bacteria
Comprehensive benchmarking single and multi ancestry polygenic score methods with the PGS-hub platform
A stabilized tandem antigen chimera that elicits potent malaria transmission-reducing activity
Abstract Malaria parasite transmission remains a barrier to elimination since asymptomatic individuals sustain the infectious reservoir. Transmission-blocking vaccine (TBV) candidates targeting Plasmodium falciparum (Pf) gametocyte surface proteins Pfs230 and Pfs48/45 have shown promise in clinical trials. Several vaccine candidates have been developed for these antigens, yet it is unclear which elicit the most robust and durable transmission-blocking responses. From structure-function relationships of monoclonal antibodies in complex with both antigens, we report the development of a stabilized tandem antigen chimera (STAC), which presents the most potent epitopes from Pfs230 domain 1 (Pfs230-D1) and Pfs48/45 domain 3 (Pfs48/45-D3) in a single construct, while masking non-functional epitopes using an engineered pseudo-native domain disposition. Iterative structure-guided optimization improved antigen yields and stability, while nanoparticle-based multimerization enhanced the functional transmission-reducing activity elicited by the immunogen in female mice. Immunizations with STAC genetically conjugated to self-assembling protein nanoparticles elicited antibodies with potent transmission-reducing activity comparable or superior to the multimerized Pfs230-D1 and Pfs48/45-D3. These findings establish STAC as a promising next-generation TBV candidate to disrupt malaria transmission and accelerate elimination efforts. More broadly, our results support the engineering of highly ordered and stable multi-domain antigens in a single protein as a strategy for the cost-efficient development of multi-component vaccines.
Comprehensive 4E performance assessment of novel porous clay bricks across new climate zones of Türkİye
Bradyzoite subtypes rule the crossroads of Toxoplasma development
Abstract Toxoplasmosis is a major risk to chronically infected individuals, especially those who become immunocompromised. Although one-third of the globe is infected with Toxoplasma , no treatments prevent or eliminate cysts in part due to limited understanding of bradyzoite biology. The cyst is central to Toxoplasmosis, as transition from bradyzoites to tachyzoites drive pathology. In this study, we aim to understand the biology of bradyzoites prior to recrudescence and the developmental pathways they initiate. Here, we discover ME49EW cysts from infected mice harbor multiple bradyzoite subtypes with distinct fates. Purified subtypes exhibit defined developmental pathways in animals and in primary astrocytes. Single-bradyzoite RNA-sequencing reveals five major subtypes within cysts. We further show that a crucial subtype in chronically infected mice is absent from a widely used in vitro model of bradyzoite development. Altogether, this work establishes new foundational principles of Toxoplasma cyst development and reactivation that operate during the intermediate life cycle of Toxoplasma .
Fecal microbiome predicts treatment response after the initiation of semaglutide or empagliflozin uptake
TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism
Abstract Triggering receptor expressed on myeloid cells 2 (TREM2) is a central regulator of microglial activity and loss-of-function coding variants are major risk factors for late onset Alzheimer’s disease (LOAD). To better understand the molecular and functional changes associated with TREM2 signalling in microglia, we generated a TREM2 reporter mouse. In APP transgenic animals, bulk RNA-sequencing of isolated microglia sorted based on reporter expression highlighted TREM2 level-related changes in major immunometabolic pathways, and enrichment of genes in oxidative phosphorylation and cholesterol metabolism in microglia with increased TREM2 expression. Metabolic and lipidomic profiling of sorted microglia showed that, independent of Aβ pathology, TREM2 expression correlated with signatures consistent with increased cellular redox, energetics, and cholesterol homoeostasis. In accordance, metabolic activity correlated with phagocytic capacity. Finally, we performed chronic treatment with a TREM2 agonist antibody and identified a window of TREM2 expression where microglia are most responsive, thereby informing clinical applications of TREM2 agonists.
Body temperature as a predictor of mortality in multiple trauma patients: a prospective single-centre cohort study
Abstract Trauma is the leading cause of death among working-age people. Individuals who have experienced trauma are more susceptible to developing accidental hypothermia. This condition has been demonstrated to be associated with poor clinical outcomes. The primary objective of this study was to identify the association between body temperature (BT) and mortality in patients with multiple trauma. A secondary objective was to ascertain whether this association remained significant in patients with body temperature < 36 °C. A prospective cohort study was conducted in a level-3-trauma centre in Barcelona, Spain, between August 2022 and February 2024. Data pertaining to demographics, out-of-hospital and in-hospital clinical variables were collected. BT was categorised as follows: <35 °C, 35–35.9 °C, 36–37 °C, and > 37 °C. Univariable and multivariable logistic regression were conducted to assess the association between BT and mortality. A sensitivity analysis was also performed using a dichotomous BT threshold of < 36 °C. The study comprised 334 patients, with an overall mortality rate of 10.4%. Secondary mortality endpoints were: 24-hour mortality in 6 patients (1.8%), 30-day mortality in 23 patients (6.9%), and in-hospital mortality in 25 patients (7.5%). Hypothermia (BT < 35 °C) was observed in 11.7% of patients, resulting in a mortality rate of 23%. Patients with BT < 36 °C constituted 43.4% of the cohort. Univariable logistic regression revealed a significant inverse relationship between BT and mortality (OR 0.51, 95% CI 0.3–0.7; P < 0.001). Following multivariable adjustment, the association remained robust (OR 0.58, 95% CI 0.37–0.91; P = 0.02). A subsequent sensitivity analysis demonstrated that a BT < 36 °C was an independent predictor of mortality (OR 3.29; 95% CI: 1.23–8.77; P = 0.017). BT was identified as an independent and significant predictor of mortality in patients with multiple trauma. For every 1 °C decrease in BT, the odds of mortality increased by 72%. Patients with a BT < 36 °C exhibited a threefold elevated probability of mortality.
Pangenome dynamics and population structure of the zoonotic pathogen Salmonella enterica serotype Hadar
Abstract The bacterial accessory genome, comprised of plasmids, phages, and other mobile elements, underpins the adaptability of bacterial populations. Pangenome (core and accessory) analysis of pathogens can reveal epidemiological relatedness missed by using core-genome methods alone. Employing a k -mer-based Jaccard Index approach to compute pangenome relatedness, we explore the population structure and epidemiology of Salmonella enterica serotype Hadar (Hadar), an emerging zoonotic pathogen in the United States (U.S.) linked to both commercial and backyard poultry. A total of 3384 U.S. Hadar genomes collected between 1990 and 2023 are analyzed here. Hadar populations underwent substantial shifts between 2019 and 2020 in the U.S., driven by the expansion of a lineage carrying a previously uncommon prophage-like element. Phylogenetic and pangenomic relatedness, coupled with epidemiological data, suggest this lineage emerged from extant populations circulating in commercial poultry, with subsequent dissemination into backyard poultry environments. We demonstrate the utility of pangenomic approaches for mapping vertical and horizontal diversity and informing complex dynamics of zoonotic bacterial pathogens.
Comparative study of palmitoleic acid, sea buckthorn oil, and lovastatin in hepatocellular steatosis model
Abstract Palmitoleic acid (POA) has been associated with various metabolic effects, including regulating lipid metabolism and cholesterol production. In this study, we explored the impact of both cis - (cPOA) and trans -palmitoleic acid (tPOA), along with sea buckthorn oil (SBO), a natural source rich in cPOA, on lipid content, metabolic activity, and Rap1 prenylation in HepG2 cells. We employed a free fatty acids-induced steatosis model. Our findings revealed that neither cPOA, tPOA, SBO, nor digested SBO impaired the metabolic activity of HepG2 cells, even under steatotic conditions. All treatments led to triacylglycerol (TAG) accumulation, with tPOA demonstrating the beneficial effect. While cholesterol levels remained unchanged in normal cells, a reduction was noted in steatotic cells, comparable to the effect of lovastatin. Molecular docking suggested that both POA isomers may bind and block the catalytic pocket of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). To further explore this, we examined their influence on Rap1 prenylation and subcellular localization. Under steatotic conditions, both POA isomers, particularly at concentrations of 50 and 100 µM, elevated cytosolic Rap1 levels, whereas no significant changes were observed in membrane or cytosolic Rap1a protein levels in normal HepG2 cultures. Notably, unlike lovastatin, POA isomers and digested SBO enhanced glucose-stimulated insulin secretion from pancreatic cells. Our results highlight the potential of POA isomers and SBO as modulators of lipid metabolism, cholesterol production, and insulin secretion, suggesting their relevance in managing metabolic disorders.
Bernoulli’s principle-mediated Cl2 electrosynthesis
Abstract Existing technologies for chlorine (Cl 2 ) synthesis are generally suffered from low productivity or high production cost. Guided by Bernoulli’s principle, here we report an efficient yet cost-effective electrochemical system for Cl 2 electrosynthesis, which is composed of anodic chlorine evolution reaction (CER) connected to gas chamber by triple-phase gas diffusion layer. The key is to modulate gas diffusion layer by Bernoulli’s principle, wherein the pressure difference at triple-phase boundary drives oriented Cl 2 migration directly into gas chamber, thus preventing the crossover of anodic/cathodic products. By further joining with a pH-tolerant catalyst, a standalone prototype device is built for high-rate Cl 2 production, operating at the Faradaic efficiencies of 96.3% ~ 87.6% in the current density range of 0.1 ~ 1.14 A cm −2 , having superior Cl 2 synthesis performance. Further technical-economic evaluations of our synthetic scheme demonstrate reduced Cl 2 production cost, saving 6.75% (1.17 million dollar per year) as comparison to conventional chlor-alkali design. We expect these findings offer broader opportunities to develop industrially production processes for other chemical commodities.
Collaborative representation and confidence-driven semi-supervised learning for hyperspectral image classification
Abstract Hyperspectral image (HSI) classification faces challenges in diverse scenarios due to spectral-spatial complexity and class imbalance. Existing methods lack generalizability. This paper presents a novel Graph-Convolutional Networks with Adaptive Region Ensembles (GCN-ARE) framework. It integrates graph spectral learning, dynamic region subdivision, and classifier fusion. The key contributions are as follows: First, a normalized graph Laplacian operator ensures graph spectral stability, bounding the eigenvalue spectrum to stabilize feature propagation and address gradient issues in irregular terrains. Second, recursive K-means clustering under empirical risk bounds achieves adaptive region optimality, dynamically partitioning complex regions for enhanced local discriminability. Third, theoretical guarantees based on Hoeffding’s inequality enable dynamic ensemble consistency, facilitating optimal classifier selection under spatial-spectral uncertainty. Experiments on four HSI datasets (Botswana, Houston, Indian Pines, WHU-Hi-LongKou) show that GCN-ARE outperforms benchmarks like ViT and GAT, with average OA improvements of 1.5–5.7%. Ablation studies confirm the importance of adaptive subdivision and ensemble modules, and parameter sensitivity analyses reveal its robustness. The framework sets a new standard for robust HSI classification with its theoretical rigor and practical efficacy.