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“I think they are infected because of their ignorance and lack of responsibility”: A mixed-methods study on HIV-related stigma in the healthcare system in Kazakhstan

Background HIV-related stigma among healthcare providers remains a significant barrier to effective HIV care and treatment. This study aimed to assess HIV-related stigma and associated factors among healthcare providers in primary healthcare clinics (PHCs) in Almaty, Kazakhstan. Methods A mixed-methods design was employed, involving quantitative surveys and qualitative in-depth interviews. Eight PHCs were randomly selected, and 448 healthcare providers participated in the survey. The cross-sectional surveys took place at the PHCs between May 2, 2019, and July 2, 2019. The sample size was predetermined statistically with a 2.5% precision using a 95% confidence level. For the qualitative component, 10 participants were chosen for in-depth interviews. Descriptive statistics, bivariate analysis, and multivariable logistic regression models were performed for quantitative data analysis. Qualitative data were analyzed through manual thematic analysis. Results The study revealed high levels of HIV-related stigma, with 87% of respondents agreeing with at least one stigmatizing statement about people living with HIV (PLHIV). Fear of HIV infection was also prevalent, with 85% of healthcare providers expressing some level of concern about contracting HIV during medical procedures. Logistic regression analysis indicated that longer years of work in healthcare were protective against stigmatizing opinions (Adjusted Odds Ratio (AOR)=0.25; 95% Confidence Interval (95%CI)=0.09,0.67; p = 0.006), while not having seen a patient living with HIV in the last 12 months was associated with higher stigma (AOR = 3.31; 95%CI = 1.73, 6.31; p < 0.001). Qualitative interviews corroborated these findings and highlighted differential attitudes towards PLHIV based on modes of transmission, with particularly negative views towards sex workers and individuals with non-traditional sexual orientations. Conclusions The study demonstrates significant HIV-related stigma among healthcare providers in Almaty PHCs, influenced by a lack of exposure to PLHIV and specific socio-demographic factors. These findings underscore the need for targeted interventions to reduce stigma and enhance HIV care in Kazakhstan.

Rising global temperatures reduce soil microbial diversity over the long term

Soil microbial diversity is crucial to sustaining ecosystem productivity and improving carbon sequestration. Global temperature continues to rise, but how climate warming affects microbial diversity and its capacity to sequester soil organic carbon (SOC) remains uncertain. Here, by conducting a global meta-analysis with 251 paired observations from 102 studies, we showed that, on average, warming reduced bacterial and fungal diversity (measured by richness and Shannon index) by 16.0 and 19.7%, respectively, and SOC by 18.1%. The negative responses of both soil bacterial and fungal diversity to warming became more pronounced with increasing warming magnitude, experimental duration, and decreasing soil nitrogen availability. Under the worst-case climate warming scenario (2010 to 2070, 3.4 increase in °C), soil bacterial diversity and fungal diversity are projected to reduce by 56% and 81%, respectively, over 60 y. Importantly, in addition to the direct impact of warming on SOC, warming-induced declines in microbial diversity also contributed to SOC losses. We highlight that prolonged warming could substantially reduce soil microbial diversity and decrease SOC sequestration, accelerating future warming and underscoring the urgent need for decisive actions to mitigate global climate change.

Beta blockers linked to reduced 1-Year mortality in critically ill congestive heart failure patients with differential benefits across subgroups

The way aesthetic needs affects the relationship between aesthetic responsiveness and creativity

Although the study of beauty and its education is expanding, there is still a scarcity of research surrounding the development of our minds and their responses to these emotions. The goal of this study was to look at how the way we respond to beauty connects with creativity, and how our need for beauty influences this connection. A total of 748 university students participated in the study conducted in China. The participants filled out anonymous surveys on a website. The surveys included three tools: the Aesthetic Needs Scale (ANS), the Aesthetic Responsiveness Assessment (AReA), and the Williams Creative Tendency Scale (WCTS). A positive connection was found between all three factors studied. Aesthetic needs play a role in how the assessment of aesthetic responsiveness relates to creativity. This means that people who score high on the aesthetic responsiveness tend to be more creative, especially if they also have strong aesthetic needs.

De novo rates of a <i>Trypanosoma</i> -resistant mutation in two human populations

Mutation rates have long been measured as averages across many genomic positions. Recently, a method to measure the rates of individual mutations was applied to a narrow region in the human hemoglobin subunit beta ( HBB ) gene containing the site of the hemoglobin S (HbS) mutation as well as to a paralogous hemoglobin subunit delta ( HBD ) region, in sperm samples from sub-Saharan African and northern European donors [Melamed et al ., Genome Res. 32 , 488–498 (2022)]. The HbS mutation, which protects against malaria while causing sickle-cell anemia in homozygotes, originated de novo significantly more frequently in the HBB gene in Africans compared to the other three test cases combined (the European HBB gene and the European and African HBD gene). Here, we apply this approach to the human apolipoprotein L1 ( APOL1 ) gene containing the site of the G1 1024A→G mutation, which protects against African sleeping sickness caused by Trypanosoma brucei gambiense while causing a substantially increased risk of chronic kidney disease in homozygotes. We find that the 1024A→G mutation is the mutation of highest de novo origination rate and deviates most from the genome-wide average rate for its type (A→G) compared to all other observable mutations in the region and that it originates de novo significantly more frequently in Africans than in Europeans—i.e., in the population where it is of adaptive significance. The results are unexpected given the notion that the probability of a specific mutational event is independent of its value to the organism and underscore the importance of studying mutation rates at the individual-mutation resolution.

Cross-sectional analysis of sociodemographic factors associated with self-reported and knowledge-based health literacy in Korea using data from KNHANES 2023

Research of text paraphrase generation based on self-contrastive learning

The goal of this study is to improve the quality and diversity of text paraphrase generation, a critical task in Natural Language Generation (NLG) that requires producing semantically equivalent sentences with varied structures and expressions. Existing approaches often fail to generate paraphrases that are both high-quality and diverse, limiting their applicability in tasks such as machine translation, dialogue systems, and automated content rewriting. To address this gap, we introduce two self-contrastive learning models designed to enhance paraphrase generation: the Contrastive Generative Adversarial Network (ContraGAN) for supervised learning and the Contrastive Model with Metrics (ContraMetrics) for unsupervised learning. ContraGAN leverages a learnable discriminator within an adversarial framework to refine the quality of generated paraphrases, while ContraMetrics incorporates multi-metric filtering and keyword-guided prompts to improve unsupervised generation diversity. Experiments on benchmark datasets demonstrate that both models achieve significant improvements over state-of-the-art methods. ContraGAN enhances semantic fidelity with a 0.46 gain in BERTScore and improves fluency with a 1.57 reduction in perplexity. In addition, ContraMetrics achieves gains of 0.37 and 3.34 in iBLEU and P-BLEU, respectively, reflecting greater diversity and lexical richness. These results validate the effectiveness of our models in addressing key challenges in paraphrase generation, offering practical solutions for diverse NLG applications.

Local c-di-GMP signaling, triggered by cross-regulation of cAMP-CRP and c-di-GMP, controls biofilm formation under nutrient limitation

Bacteria have several nucleotide second messengers, most of which act as global regulators to control a wide range of bacterial physiological processes. Studies usually focus on a single second messenger, and the mechanisms and physiological significance of the cross-regulation between different nucleotide second messengers are often unclear. Here, we show that Shewanella putrefaciens can form biofilms in both nutrient-rich and nutrient-poor media. While both are controlled by c-di-GMP, the regulatory models differ. Under low nutrient conditions, cross-regulation of cAMP-CRP and c-di-GMP occurs at the transcriptional and posttranslational levels, thereby controlling biofilm development. During the early stages of biofilm development, cAMP-CRP directly promotes the transcription of a PDE gene, lrbR , by LrbA. Additionally, cAMP-CRP recruits LrbR to BpfD to suppress early biofilm formation via LrbR-dependent local degradation of c-di-GMP. Finally, as intracellular LrbR levels decrease, cAMP-CRP-BpfD enables a rapid shift to biofilm development and supports biofilm maintenance. Under high nutrient conditions, this cross-regulation does not occur, resulting in a positive correlation between global c-di-GMP levels and biofilm biomass. The identification of distinct modes of biofilm regulation in different nutrients will provide a theoretical basis for future targeted control of biofilm formation in different nutrient environments.

Mechanical response mechanism and parameter optimization of double-arch tunnels without middle drift during construction

Bycatch survival of shortfin mako sharks (Isurus oxyrinchus) in the U.S. Atlantic pelagic longline fishery

Severe population declines of shortfin mako sharks (Isurus oxyrinchus) in the Atlantic Ocean have led to the implementation of conservation measures, notably fishing retention bans and live-release regulations, aimed at substantially reducing fishing mortality to allow stock recovery. While retention bans can eliminate harvest mortality, their effectiveness can be reduced if survival of sharks encountered as bycatch and not retained is low. We quantified at-vessel survival (AVS) and post-release survival (PRS) and estimated overall bycatch survival probability of mako sharks for the U.S. Atlantic pelagic longline fishery. Based on fisheries observer records (n = 7821) between 2000–2020, we found AVS varied regionally from 0.77 (95% CI: 0.74–0.80) in the northmost observation region to 0.65 (95% CI: 0.61–0.69) in the Gulf of Mexico (GOM). We found significant negative correlations between AVS and soak time, surface temperature, mainline length, and shark size. Based on pop-up archival satellite tags (n = 27) deployed from pelagic longline vessels in the WNA during 2022–2024, PRS was 0.87 (95% CI: 0.74–0.93). Overall mean bycatch survival probability varied regionally from 0.64 (95% CI: 0.51–0.68) in the northmost observation region to 0.59 (95% CI: 0.49–0.64) in the GOM, which given the low productivity rates of mako sharks may be low enough to hinder recovery efforts if mako sharks are encountered as bycatch in significant numbers. Pairing retention bans with actions that reduce incidence of bycatch would likely provide the greatest benefit to population recovery. Our research highlights the importance of quantifying survival regionally and between fleets, as variability in fishing practices and environmental conditions can result in different bycatch survival outcomes, which can be important considerations in stock assessment.

Loss of ICOSL expression in the progression to cervical carcinoma

Human papillomavirus (HPV)–related lesions contain types with benign outcomes and those with a risk of progression to cancer. We addressed the role of immune surveillance in 76 cervical biopsies (normal = 23, HPV+ benign = 16, HPV+ precancer = 37) by studying the infiltration of cytotoxic T cells and the expression of the immune modulators PDL1, ICOSL, and miR-155 and compared the data to 101 cervical squamous cell carcinomas. In the normal cervix, ICOSL expression was restricted to the endocervical epithelia whereas neither miR-155 nor PDL1 were detected. MiR-155 was up-regulated in both the benign (88%) and precancerous (92%) HPV squamous intraepithelial lesions (SIL) and colocalized to cells in the upper part of the lesion that is the area with productive viral infection. Both PDL1 (95%) and ICOSL (89%) were only evident in the precancerous SIL and each localized to squamous cells in the basal aspect that lacked replicating virus. In both microinvasive and invasive cervical squamous cell cancer miR-155 expression remained high (83%) as did PDL1 expression (80%) but ICOSL detection was reduced to 17%. Infiltration by CD8+ T cells was intense in the invasive lesions and these cells were mostly inactive as determined by the lack of granzyme B colocalization. It is concluded that miR-155 expression is a marker of HPV infection in both benign and precancerous lesions, whereas the approximately 10% of the latter lesions that progress to cancer gain PDL1 and lose ICOSL expression, which are important factors in avoiding immune surveillance.

A potential age-independent MASLD-related liver fibrosis index based on metabolic profiling

Integrated comparative analysis of T-staging of laryngeal carcinoma on parallel versus non-parallel vocal cord CT planes with its potential treatment pitfalls

Accurate CT staging plays a crucial role in guiding effective management of laryngeal carcinoma, as endoscopic assessment alone may not provide a comprehensive evaluation of tumor spread. Consequences of non-compliance to parallel vocal cord plane for tumors remained unexplored in existing literature. We aimed to compare T-staging parameters of laryngeal carcinoma on CT neck in non-parallel and parallel to vocal cord axial planes and analyse degree of discrepancy between them. We retrospectively studied 34 larynges with squamous cell carcinoma on non-parallel plane① and parallel to vocal cord plane② axial CT scan. Quantitative (anteroposterior AP, transverse Tr, anterior commissure ACom) and qualitative (site, intralaryngeal and extralaryngeal extension) T-staging variables were interpreted in both planes and differences between them were registered. Kappa analysis was employed to get level of disagreement between tumor reporting of each plane. There was minimal to worse agreement between T-staging in these planes (k = −0.059 to 0.353). Difference between means of ACom was significant, but not AP and Tr dimensions. Categorical variables in plane② showed majority of glottic origin (70.5%) and T1a (38.2%) stage, while plane① had subglottic (52.9%) and T2 (41.1%). Overall plane① showed 41.1% altered staging (mostly T1,T2), out of which 71.2% were upstaged. Rest unaffected larynges (28.8%, n = 20) showed either change in origin (41.2%) or ACom involvement (58.8%). Consequently, 73.5% (n = 25) patients in plane ① manifested at least one change, so can jeopardise targeted management. Results established that non-adherence to reporting on parallel CT larynx can result in significant variability in principal qualitative and quantitative T-stage tumor parameters, hence imperiling patients to over or undertreatment.

CryoEM structure of ALK2:BMP6 reveals distinct mechanism that allow ALK2 to interact with both BMP and activin ligands

Ligands in the transforming growth factor β (TGF-β) family [activins, Bone Morphogenetic Proteins (BMPs), and TGF-βs] signal by bringing together two type I and two type II receptors. Activin receptor-like kinase-2 (ALK2) is the only type I receptor among the seven TGF-β type I receptors that interacts with both activin and BMP ligands. With BMPs, ALK2 acts as a signaling receptor to activate small mothers against decapentaplegic 1 (SMAD1)/5/8 signaling. Alternatively, with activins, such as Activin A (ActA), ALK2 forms nonsignaling complexes that negatively regulate ALK2 and ActA signaling. To gain insight into how ALK2 interacts with two distinct classes of ligands, we resolved the cryoelectron microscopy structure of ALK2 in complex with the type II receptor, ActRIIB, and the ligand, BMP6, in parallel with the corresponding structure with ALK3 for direct comparison. These structures demonstrate that ALK2 and ALK3 utilize different mechanisms to interact with BMP6 at the wrist interface, with ALK2 relying on BMP6 glycosylation and ALK3 relying on a salt bridge. Modeling of ALK2:ActA reveals that binding relies on ActA’s fingertip region, mirroring the interaction of ActA with its other receptor, ALK4. Our results demonstrate that ALK2 is a “hybrid” receptor that incorporates features of BMP type I receptors such as ALK3 at the wrist interface and an activin type I receptor such as ALK4 at the fingertip.

Evaluating the ability of large Language models to predict human social decisions

Mechanism of Huanglian Wendan Decoction in ameliorating non-alcoholic fatty liver disease via modulating gut microbiota-mediated metabolic reprogramming and activating the LKB1/AMPK pathway

Background Huanglian Wendan Decoction (HLWDD), a classical traditional Chinese medicine (TCM) formula, has shown therapeutic promise in treating metabolic disorders. However, its underlying mechanisms against non-alcoholic fatty liver disease (NAFLD) remain unclear. Objective This study aimed to elucidate the pharmacological mechanisms by which HLWDD ameliorates NAFLD, focusing on its impact on lipid metabolism, gut microbiota, and amino acid regulation. Methods A NAFLD rat model was established by administering a high-sugar, high-fat, high-salt diet for 20 weeks. The core components of HLWDD were identified and quantified using UPLC-Q-TOF-MS/MS and HPLC, and further validated via network pharmacology and molecular docking. Therapeutic efficacy was assessed through analysis of body weight, serum lipid profiles, inflammatory cytokines, hepatic histology, and protein expression. Gut microbiota composition and liver-intestine metabolite profiles were evaluated using metagenomic sequencing and LC-MS/MS. Results Seven key constituents, including quercetin and berberine, were quantified (15.11–164.37 μg/mL) and shown to interact with lipid metabolism targets such as liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor alpha (PPARα), and carnitine palmitoyltransferase 1A (CPT1A). HLWDD treatment significantly reduced body weight, hepatic lipid accumulation, and serum levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol, while increasing high-density lipoprotein cholesterol. Proinflammatory cytokines (IL-6, IL-1β, TNF-α) were notably suppressed. Mechanistically, HLWDD activated the LKB1/AMPK signaling pathway and modulated aspartic acid metabolism in association with increased abundance of Akkermansia in the gut. Metabolomic analysis identified 13 differential metabolites, with aspartic acid showing strong correlations with Akkermansia and LKB1/AMPK activity. Conclusion HLWDD exerts its anti-NAFLD effects by enhancing Akkermansia-mediated aspartate metabolism, thereby activating the LKB1/AMPK axis and promoting lipid oxidation via CPT1A and PPARα. This study provides new mechanistic insight into the gut–liver axis in NAFLD and highlights HLWDD as a multi-targeted therapeutic approach for restoring metabolic balance.

Cohort mortality forecasts indicate signs of deceleration in life expectancy gains

The fast-paced improvements in mortality in high-income countries since the early 1900s have led to a sustained increase in life expectancy. However, whether this linear trend will continue or life expectancy gains will decelerate in the near future remains unclear. To answer this question, we apply multiple established and recently developed mortality forecasting methods to estimate cohort life expectancy for individuals born between 1939 and 2000 in 23 high-income countries. Across all forecasting methods, our results robustly and consistently indicate a deceleration in cohort life expectancy. The previously observed pace of improvement, 0.46 y per cohort, declines by 37% to 52%, depending on the method used. Robustness checks suggest that these findings are unlikely to be solely due to downward bias in cohort life expectancy forecasts. Furthermore, an age-decomposition analysis indicates that this deceleration is primarily driven by a slower pace of mortality improvement at very young ages. Over half of the total deceleration is attributable to mortality trends under age 5, while more than two-thirds is explained by mortality trends under age 20. This pattern had already emerged in the observed data for the cohorts included in our analysis. Thus, even if these estimates turned out to be overly pessimistic, it is unlikely that the deceleration will reverse in the near future.

Perceived risk of cardiovascular diseases and its determinants in Hookah users in Southwest of Iran

Efficacy of Pulsatilla saponin B4 for treatment dairy cows affected with clinical mastitis

In order to explore the therapeutic effect of natural compound Pulsatilla saponin B4 (PSB4) on clinical mastitis (CM) in dairy cows, 40 dairy cows with CM and 20 healthy dairy cows were selected as experimental samples in a large dairy farm. The CM cows were randomly divided into two groups (20 cows in each group), namely the PSB4 group treated with PSB4 neck intramuscular injection and the positive drug (PC) group treated with ceftiofur sodium neck intramuscular injection as a positive control. Another 20 healthy dairy cows were neck intramuscular injected with the same amount of normal saline to serve as a normal control (NC) group. The treatment duration was 7 days. The body temperature and milk yield of all cows were recorded on days 0, 4 and 7, while blood and milk samples were collected for the determination of relevant laboratory indicators, including somatic cell count (SCC), pathogenic microorganisms, immune factors, cytokines, antioxidant indexes, hematological and biochemical indexes. The results showed that PSB4 effectively restored the body temperature of diseased cattle, reduced SCC, significantly increased milk yield, effectively inhibited pathogenic bacteria, and significantly restored the levels of serum C-reactive protein (CRP), interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α); immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM); total antioxidant capacity (T-AOC), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and other indicators. In addition, some indicators of blood routine and blood biochemistry also returned to normal levels. In summary, PSB4 has a significant therapeutic effect on CM in dairy cows, and has a similar effect to the positive drug, which can provide a new strategy for reducing the use of antibiotics in dairy cattle farms.

Community detection for directed networks revisited using bimodularity

Community structure is a key feature omnipresent in real-world network data. Plethora of methods have been proposed to reveal subsets of densely interconnected nodes using criteria such as the modularity index. These approaches have been successful for undirected graphs but directed edge information has not yet been dealt with in a satisfactory way. Here, we revisit the concept of directed communities as a mapping between sending and receiving communities. This translates into a definition that we term bimodularity. Using convex relaxation, bimodularity can be optimized with the singular value decomposition of the directed modularity matrix. Subsequently, we propose an edge-based clustering approach to reveal the directed communities including their mappings. The feasibility of the framework is illustrated on a synthetic model and further applied to the neuronal wiring diagram of the Caenorhabditis elegans , for which it yields meaningful feedforward loops of the head and body motion systems. This framework sets the ground for the understanding and detection of community structures in directed networks.