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Pretreatment expression of miR-191a may predict response to the induction chemotherapy based on cytarabine in acute myeloid leukemia patients – a single-center pilotal study

PLoS ONE Agnieszka Szymczyk, Sylwia Chocholska, Katarzyna Radko et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0324320

Background Acute myeloid leukemia (AML) is associated with the accumulation of acquired genetic disorders. Moreorver chromosomal and molecular changes are independent prognostic factors that are taken into account to determine prognosis and treatment. MicroRNAs are novel gene regulators, which have been recognized to play an important role in pathological leukemogenesis. This study is aimed to analyze the possible role of micro RNAs as a markers predicting the outcome to induction chemotherapy based on cytarabine. Materials and methods The expression of miR-34a, miR-191, miR-199a and miR-199b in previously separated bone marrow cells was assessed at the moment of diagnosis in 44 AML patients with use of qRQ-PCR technique. Assessment of response to induction therapy was based on criteria for response to treatment proposed by European LeukemiaNet (ELN). Results Only the expression level of miR-191a out of all analyzed microRNAs was significantly associated with the induction chemotherapy response. We detected also significantly higher expression of miR-191 in FLT3-ITD negative group in comparison to FLT3-ITD positive subjects. For miR-34a, miR-199a and miR-199b, no relationship was found between their expression and FLT3-ITD, NPM1 and CEBPA mutations. It was also shown that in the group of patients with low miR-191 expression, the number of myeloblasts was higher (p < 0.05). Conclusions These results may prove an important role of miR-191a expression as a predictor of response to the induction chemotherapy based on cytarabine, even in cases when other risk factors are absent.

Diagnosis of knee meniscal injuries using artificial intelligence: A systematic review and meta-analysis of diagnostic performance

PLoS ONE Soheil Mohammadi, Ali Jahanshahi, Mohammad Shahrabi Farahani et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0326339

Aim of the study The aim was to systematically review the literature and perform a meta-analysis to estimate the performance of artificial intelligence (AI) algorithms in detecting meniscal injuries. Materials and methods A systematic search was performed in the Scopus, PubMed, EBSCO, Cinahl, Web of Science, IEEE Xplore, and Cochrane Central databases on July, 2024. The included studies’ reporting quality and risk of bias were evaluated using the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) and the Prediction Model Study Risk of Bias Assessment Tool (PROBAST), respectively. Also, a meta-analysis was done using contingency tables to estimate diagnostic performance metrics (sensitivity and specificity), and a meta-regression analysis was performed to investigate the effect of the following variables on the main outcome: imaging view, data augmentation and transfer learning usage, and presence of meniscal tear in the injury, with a corresponding 95% confidence interval (CI) and a P-value of 0.05 as a threshold for significance. Results Among 28 included studies, 92 contingency tables were extracted from 15 studies. The reference standard of the studies were mostly expert radiologists, orthopedics, or surgical reports. The pooled sensitivity and specificity for AI algorithms on internal validation were 81% (95% CI: 78, 85), and 78% (95% CI: 72, 83), and for clinicians on internal validation were 85% (95% CI: 76, 91), and 88% (95% CI: 83, 92), respectively. The pooled sensitivity and specificity for studies validating algorithms with an external test set were 82% (95% CI: 74, 88), and 88% (95% CI: 84, 91), respectively. Conclusion The results of this study imply the lower diagnostic performance of AI-based algorithms in knee meniscal injuries compared with clinicians.

Genetic markers for knee osteoarthritis presence are not associated with disease progression - data from the IMI-APPROACH cohort

PLoS ONE Mieke L. M. Bentvelzen, Paco M.J. Welsing, Philippe Moingeon et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0325819

Objective Knee osteoarthritis (OA) is a heterogeneous disease with different endotypes and phenotypes, resulting in patients’ varying clinical and structural progression. Several genomic markers have been associated with knee OA presence. This study aimed to find new associations of these genetic markers with knee OA progression and to investigate the risk of knee OA progression using a polygenic risk score (PRS). Methods Data from knee OA patients (n = 297) from the IMI-APPROACH cohort with detailed measurements on disease progression were used. Knee OA progression definitions were based on the decrease in minimum joint space width in mm (minJSW; primary outcome), increase in pain on the Knee injury and Osteoarthritis Outcome Score (KOOS), and presence of radiographic OA (based on the Kellgren-Lawrence score) over 24 months. 30 previously reported single nucleotide polymorphisms (SNPs) associated with presence of OA irrespective of affected joints or knee OA specifically were investigated. We performed a SNP based genome-wide association analysis using the disease progression definitions. Furthermore, a PRS was created using the 30 presence SNPs to predict knee OA progression. Results Existing genetic markers for knee OA presence were not found to be associated with knee OA progression. The PRS of the SNPs for knee OA presence did also not show significant predictive value for knee OA progression. Unexpectedly, nineteen different variants were associated significantly (P < 5 × 10−8) with minJSW decrease. Ten SNPs are located near protein coding genes PLCL2, CDYL2, and NTNG1, and several SNPs are located in or near long non-coding RNAs (lncRNA). Conclusions The 30 OA risk SNPs individually and combined in a PRS are not associated with progression of knee OA in the IMI-APPROACH cohort. 19 different SNPs were associated with minJSW decrease. We demonstrated how to employ multiple bioinformatics tools to, despite a limited dataset, still prioritise potential biomarkers for associations to knee OA progression.

MVT-Net: A novel cervical tumour segmentation using multi-view feature transfer learning

PLoS ONE Yao Yao, Yunzhi Chen, An Yang et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0325424

Cervical cancer is one of the most aggressive malignant tumours of the reproductive system, posing a significant global threat to women’s health. Accurately segmenting cervical tumours in MR images remains a challenging task due to the complex characteristics of tumours and the limitations of traditional methods. To address these challenges, this study proposes a novel cervical tumour segmentation model based on multi-view feature transfer learning, named MVT-Net. The model integrates a 2D global axial plane encoder-decoder network and a 3D multi-scale segmentation network as source and target domains, respectively. A transfer learning strategy is employed to extract diverse tumour-related information from multiple perspectives. In addition, a multi-scale residual blocks and a multi-scale residual attention blocks are embedded in the 3D network to effectively capture feature correlations across channels and spatial positions. Experiments on a cervical MR dataset of 160 images show that our proposed MVT-Net outperforms state-of-the-art methods, achieving a DICE score of 75.9±7.43%, an ASD of 2.69±0.58 mm and superior performance in tumour localisation, shape delineation and edge segmentation. Ablation studies further validate the effectiveness of the proposed multi-view feature transfer strategy. These results demonstrate that our proposed MVT-Net represents a significant advance in cervical tumour segmentation, offering improved accuracy and reliability in clinical applications.

Characterization of the Pank2-/- mouse retinal phenotype as a pre-clinical model for pantothenate kinase-associated neurodegeneration

PLoS ONE Grace Li-Na Su, Suh Young Jeong, Dahlia Wafai et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0326866

Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive movement and vision disorder in the neurodegeneration with brain iron accumulation family of diseases. PKAN is caused by mutations in PANK2, encoding pantothenate kinase 2, causing an inborn error of coenzyme A metabolism and leading to iron accumulation in the basal ganglia. Peripheral pigmentary retinopathy is common in people with PKAN. The knockout murine model of the orthologous Pank2 gene is known to manifest retinal degeneration through electroretinography, pupillary response and histology analyses. Our longitudinal characterization of the retinopathy in this model reveals reduced visual performance and reduced photoreceptor thickness compared to wild-type mice. Additionally, retinal perturbations in coenzyme A metabolism and dopamine metabolism pathways mimic those previously observed in the brain. These data extend the murine ocular phenotype associated with loss of function of Pank2. With a measurable behavioral, structural and mechanistic retinal phenotype, this mouse model is an ideal pre-clinical model that can be used to evaluate therapeutics for PKAN.

Genetic profiling of inherited colorectal cancer syndromes in Tunisian patients

PLoS ONE Rania Abdelmaksoud-Dammak, Nihel Ammous-Boukhris, Amena Saadallah-Kallel et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0326343

Objective Colorectal cancer (CRC) is among the most commonly diagnosed cancers worldwide, with 2% to 5% of cases being linked to inherited syndromes. Material and methods A cohort of 30 Tunisian patients was selected and divided into two groups based on clinical features and family history: Group 1 included patients clinically diagnosed with hereditary polyposis syndromes, including MUTYH-Associated Polyposis (MAP: 15 cases) and Familial Adenomatous Polyposis (FAP: 5 cases). Group 2 consisted of patients clinically diagnosed with non-polyposis syndromes, including Lynch Syndrome (LS: 7 cases) and other rare syndromes (OS: 3 cases). Genetic testing was performed using either Sanger sequencing or targeted next-generation sequencing (NGS) with a cancer panel including 31 cancer-related genes. Results In Group 1, MAP was confirmed in 13 patients who were homozygous carriers of the pathogenic variant (c.1143_1144dup p.Glu382fs) in the MUTYH gene. For patients suspected of having FAP, pathogenic variants in the APC gene were identified in only two patients (c.3183_3187del p.Lys1061_Gln1062insTer, and c.2016_2017del p.His672Ter), while another patient carried a frameshift variant (c.502_503del, p.Ile168SerTer11) in the PTEN gene, indicating Cowden Syndrome. In Group 2, genetic testing confirmed Peutz-Jeghers Syndrome in a young girl who had a large deletion in the STK11 gene. For patients suspected to have LS, only variants of unknown significance (VUS) were identified in MMR. Further genetic investigations are required to identify the pathogenic variant in these patients. Conclusion Overall, our results highlight the importance of genetic testing to better understand hereditary CRC syndromes in Tunisian families, and to improve the management of patients and their relatives.

Predicting podoplanin expression and prognostic significance in high-grade glioma based on TCGA TCIA radiomics

PLoS ONE Shengrong Long, Hongyu Xu, Mingdong Li et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0325964

Background Podoplanin (PDPN) is a membrane glycoprotein implicated in tumor invasion and immune modulation in high-grade gliomas (HGGs). However, the non-invasive prediction of PDPN expression and its prognostic significance using radiomics remains unexplored. Materials and methods This study used preoperative contrast-enhanced MRI T1WI data analyzed by gradient boosting machine to predict podoplanin (PDPN) expression and overall survival (OS) in HGG patients. Results We retrospectively analyzed 89 HGG patients’ clinical data, MRI images, and RNA-seq profiles from TCIA. For each patient, 107 radiomics features were extracted from HGG subregions. The radiomics prognostic model was built using two selected features, glcm_Idmn and glcn_Idn. Through validation with external the REMBRANDT dataset (n=39), the model demonstrated great predictive performance for the PDPN expression levels and OS in HGG. The area under the curve of the ROC in the radiomics signature combined with clinical risk factors for the 1-year, 2-year, and 3-year OS rates in the TCIA-HGG were 0.799, 0.883, and 0.923, respectively. Gradient boosting machine using preoperative MRI T1WI and extracted radiomics features performed well in predicting the expression of PDPN and OS in HGG. Conclusions Radiomics features extracted from MRI images can non-invasively predict PDPN expression and prognosis in HGG, offering a potential imaging biomarker for individualized clinical management.

Estimation of the future prevalence of diabetes based on data from the Brazilian Study of Cardiovascular Risk Factors in Adolescents (ERICA)

PLoS ONE Barbara Pozzi Ottavio, Stéfani Sousa Borges, Márcia Gisele Santos da Costa et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0326436

Introduction Diabetes is a significant public health issue due to its high prevalence and multifaceted consequences, impacting both the Brazilian Unified Health System and society. The disease adversely affects people's quality of life and elevates healthcare costs. In 2019, approximately 16 million Brazilians were diagnosed with diabetes mellitus. Understanding the future trends of this disease is crucial for planning effective preventive interventions. This paper aims to estimate the future prevalence type 2 diabetes mellitus on individuals from the Study of Cardiovascular Risk Factors in Adolescents (ERICA) sample, based on the progression of their cardiovascular risk factors. Method A literature review was conducted to identify predictive models for type 2 diabetes mellitus that utilize cardiovascular risk factors assessed during adolescence to forecast diabetes risk in adulthood. A logistic regression model, grounded in the natural history of clinical variables derived from longitudinal studies, was applied to each individual to determine their risk of developing type 2 diabetes mellitus. Additionally, probabilistic and deterministic sensitivity analyses were performed, incorporating the minimum and maximum values of model parameters. Results The predictive model estimated that 15.12% of individuals in the ERICA sample are likely to develop type 2 diabetes mellitus in adulthood, with a range of 1.1% to 28% based on sensitivity analyses. The parameters exerting the most significant influence on these results included diastolic blood pressure and triglycerides, followed by LDL cholesterol and systolic blood pressure. Conclusion The application of this predictive model to the Study of Cardiovascular Risk Factors in Adolescents (ERICA) sample indicates an estimated prevalence of 15.12% for T2DM over a 20.5-year follow-up period. Studies like this one provide valuable insights for designing targeted interventions to mitigate the progression of diabetes and its associated socioeconomic impacts.

Evaluation of the prevalence of MASLD, MASH and liver fibrosis in a Dutch bariatric cohort

PLoS ONE Willy Theel, Willem-Pieter Brouwer, Elisabeth van Rossum et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0324813

Background and aims The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) in bariatric populations has been widely studied but may vary geographically. This study evaluates MASLD/MASH prevalence and the utility of non-invasive tests (NITs) for liver fibrosis in a Dutch bariatric surgery cohort. Methods This single-center cross-sectional diagnostic accuracy study included 220 patients undergoing bariatric surgery. At baseline, 10 NITs were performed. Patients with liver stiffness measurements ≥ 8kPa using vibration-controlled transient elastography underwent a liver biopsy during surgery. Histology was assessed using the nonalcoholic fatty liver disease Activity Score. Diagnostic accuracy of NITs was evaluated against histology using sensitivity, specificity, and area under the receiver operating characteristic (AUROC). MASH was defined as steatosis with lobular inflammation and ballooning, with or without fibrosis. At-risk MASH included fibrosis ≥F2. Results Out of 77 patients (35%) eligible for histological analysis, the findings revealed a MASLD prevalence of 50.6%, MASH prevalence of 5.3%, and at-risk MASH prevalence of 2.6%. Most patients had no fibrosis (67.1%), while others exhibited mild fibrosis (F1: 23.7%, F2: 9.2%). Capped MAF-5 effectively identified fibrosis stage ≥2 (AUROC: 0.809), surpassing FIB-4 (AUROC: 0.645). Both the FAST score and capped MAF-5 demonstrated strong performance in detecting at-risk MASH. Conclusion MASLD/MASH prevalence and advanced fibrosis were lower than expected in this Dutch cohort. Capped MAF-5 demonstrated superior performance for fibrosis detection, while transient elastography and FIB-4 were less reliable. Further studies are needed to optimize NIT selection in bariatric populations.

Determinants of cervical cancer screening utilisation among women in the least developed countries: A systematic review and meta-analysis

PLoS ONE Tika Rana, Dorothy Ngo Sheung Chan, Bernard Man Hin Law et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0321627

Background and aims Globally, cervical cancer is the fourth most common cancer among women, and more than 90% of all cervical cancer-related deaths worldwide are recorded in resource-limited countries. The present review investigated the uptake rate of cervical cancer screening and identified the factors associated with screening service utilisation in the female populations of least developed countries (LDCs). Methods Five electronic databases (EMBASE, Ovid MEDLINE, CINAHL, Cochrane Library, and PubMed) and grey literature were searched for relevant literature using the keywords of the included studies. Both qualitative and quantitative studies were included. Three reviewers performed critical appraisals using the Mixed Methods Appraisal Tool. Meta-analysis was performed to pool the quantitative results from comparable studies. Results A total of twenty-five studies were included in the review. The cervical cancer screening uptake rate in LDCs ranged from 4% to 21%. Multiple factors were associated with screening service utilisation among women in the LDCs, namely socio-demographic characteristics, including employment status (odds ratio (OR): 2.72; 95% CI: 1.97–3.76; p < 0.001); knowledge of cervical cancer and its screening (OR: 3.39; 95% CI: 2.00–5.75; p < 0.001); sexual and reproductive health-related factors such as parity status (OR: 2.73; 95% CI: 1.61–4.64; p = 0.002); healthcare providers’ recommendations (OR: 5.32; 95% CI: 2.44–11.58; p < 0.001); perceived risk of developing cervical cancer (OR: 3.76; 95% CI: 2.62–5.38; p < 0.001); use of media for cervical cancer screening promotion, including radio; cultural factors; and myths and misconceptions about cervical cancer and its screening. Conclusions The uptake of cervical cancer screening among eligible women in the LDCs was notably low. The governments of these countries are advised to invest and allocate additional resources to advance policies and develop cervical cancer prevention programmes that are accessible, affordable, and acceptable.

New approach to the development of tailor-made feed for fish larvae using Zebrafish Danio rerio as a model

PLoS ONE Giovanni S. Molinari, Michal Wojno, Macdonald Wick et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0326665

Protein hydrolysates have been used extensively as dietary protein for larval fish. Typically, they are expensive, difficult to produce, and show varying results when utilized for different species. This study proposed a practical hydrolysis method that utilizes endogenous enzymes within the body to “auto-hydrolyze”, or digest its tissue proteins with its own endogenous enzymes, and produce a fishmeal tailored to nutritional requirements and absorptive capacity of larval fish. The objectives for this experiment were to determine the: 1) effect of the proposed hydrolysis method on tissue protein breakdown level; and 2) effect of dietary inclusion of obtained hydrolysates on larval growth performance, using Zebrafish (Danio rerio). Whole-body adult Zebrafish were utilized to produce an unhydrolyzed fishmeal, and three fishmeals hydrolyzed for 1, 2, and 3 h, respectively. Three diets were formulated, defined by their dietary protein supply. The Unhydro diet contained unhydrolyzed Zebrafish meal. The 50% Hydro diet contained 50% Zebrafish meal hydrolysates and 50% unhydrolyzed Zebrafish meal. The 100% Hydro diet contained 100% Zebrafish meal hydrolysates. Five groups were utilized in this study, with three groups receiving one of the produced Zebrafish meal-based diets. Larvae fed a commercial starter diet and Artemia, respectively, were included as reference groups. Larval fish were randomly stocked into tanks (100 fish per tank) at 3 days-post-hatch (dph), and the trial was carried out until 18 dph. Electrophoretic analysis showed that the proposed hydrolysis method was able to efficiently hydrolyze the protein within Zebrafish body. The feeding trial results found no significant differences in weight, total length, or survival between the Unhydro, 50% Hydro, and 100% Hydro groups. The proposed hydrolysis method provides a practical and potentially cost-effective approach to producing species-specific fishmeal hydrolysates. Further research is necessary to determine whether the produced hydrolysates can improve the growth of larval fish in other species.

Computational design and cheminformatics profiling of omeprazole derivatives for enhanced proton pump inhibition of potassium-transporting ATPase alpha chain 1

PLoS ONE Mahmudul Hasan, Md. Ifteker Hossain, Noimul Hasan Siddiquee et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0326655

Proton pump inhibitors are essential for treating moderate-to-severe gastroesophageal reflux, peptic ulcers, esophagitis, and related conditions by increasing gastric pH and inhibiting hydrogen ion discharge into the stomach. However, prolonged use may lead to adverse effects along with reduced efficacy. Our research investigates the strategic modification of omeprazole (OMP) derivatives to improve their binding affinity to targeted proteins, thereby enhancing their chemical reactivity, stability, and toxicity profiles. A total of 22 novel OMP analogues were designed through structural alterations, focusing on the benzimidazole and pyridine rings. The geometrical attributes of the analogues were further confirmed through spectral and quantum computational analysis based on density functional theory (DFT) and a B3LYP/6-31G+ G (d, p) basis set. The molecular docking with PTAAC1 presented that most of the analogues had similar or higher binding affinities and nonbonding interactions, including OMP3, OMP19, and OMP21, with binding energies of -7.3, -8.3, and -8.1 kcal/mol compared to the OMP at -7.1 kcal/mol. Pharmacokinetic, biological, and toxicological profiles via ADMET and PASS predictions also demonstrated increased safety and therapeutic potential. MD simulation also showed good stability of OMP3, OMP19, and OMP21 in binding to PTAAC1, and the RMSD, RMSF, ligand RMSD, rGyr, SASA, MolSA, PolSA, and hydrogen bond analysis also suggested superior drug potential compared to OMP. Additionally, the post-simulation MM/GBSA analysis revealed that OMP3 (-36.91 kcal/mol) outperformed OMP19 (-26.45) and OMP21 (-12.61). The protein binding site’s high stability and elevated negative binding free energy value further indicate a robust compound-protein interaction with OMP3. However, principal component analysis (PCA) showed the highest variance for OMP21, accounting for 50.66%, 21.58%, and 6.51%, respectively, for PC1, PC2, and PC3. These findings could lead to the development of OMP3 and OMP21 as potential next-generation PPIs with enhanced pharmacological activity and improved side-effect profiles, necessitating more in vitro and in vivo testing.

Design and experiment of spiral conveying pipe in pneumatic centralized fertilizer discharge system

PLoS ONE Longmei Zhang, Wensheng Yuan, Yugang Feng et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0320126

To address the problem of poor fertilizer uniformity caused by vibration and skewing during rice transplanter operations, this study developed a pneumatic centralized spiral fertilizer discharge system. By leveraging the combined effects of high-speed swirling airflow and a spiral conveying pipe, the system generates a high-speed rotating air–fertilizer mixed flow, mitigating the negative effects of ground unevenness and machine vibration on fertilizer performance. Through multi-parameter coupled simulation experiments, the optimal working parameters for the spiral conveying pipe were identified as follows: a spiral pipe length of 444.35 mm, a cross-sectional slope angle of 26°, an airflow velocity of 35 m s−1, and a screw pitch of 105 mm, achieving a coefficient of variation of 4.61%. To simulate complex field environments, comparative bench experiments were conducted between the spiral conveying pipe and the smooth straight pipe. The results showed that, at inclination angles of 0°, 5°, 10°, and 15°, the coefficients of variation for the spiral conveying pipe were 4.53%, 5.87%, 8.47%, and 9.64%, respectively, significantly outperforming the smooth straight pipe. Compared to the smooth straight pipe, the spiral conveying pipe reduced the coefficients of variation by 50.81%, 54.07%, 44.53%, and 50.54%, respectively. Field experiments demonstrated that the coefficient of variation for the spiral conveying pipe was 5.27%, representing a 63.1% reduction compared to the 14.28% recorded for the smooth straight pipe. The results confirm the effectiveness of the spiral conveying pipe’s structural design and its superior fertilizer performance, making it highly suitable for complex paddy field environments.

Correction: Investigating the association between diabetes and carpal tunnel syndrome: A systematic review and meta-analysis approach

PLoS ONE Elaheh Sanjari, Hadi Raeisi Shahraki, Lusine G. Khachatryan et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0326976

Does urban density always boost smart productivity? Evidence of an inverted U-shaped relationship in Chinese cities

PLoS ONE Tao Chen, Yike Zhang, Yaoning Yang et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0326606

Does urban density always boost smart productivity? Based on panel data from 28 major Chinese cities (2011–2021), this study reveals an inverted U-shaped relationship between urban density and smart productivity. Using entropy weight method, we construct comprehensive indices to measure both urban density and smart productivity levels. Our findings demonstrate that urban density positively influences smart productivity up to a threshold of 0.497, beyond which the relationship becomes negative. The results from fixed effects modeling show that a 1% increase in urban density is associated with a 0.114% increase in smart productivity before reaching the threshold. Through mediation analysis, we find that urbanization level serves as a significant mediator, accounting for 49.1% of the total effect. Furthermore, heterogeneity analysis reveals distinct regional patterns: urban density exhibits stronger positive effects in western regions (coefficient = 0.181) compared to central regions (coefficient = 0.156), while showing negative impacts in eastern regions. These findings suggest that optimal urban density levels vary across regions, and cities should adopt differentiated development strategies accordingly. Our study contributes to the literature by quantifying the non-linear relationship between urban density and smart productivity, while providing empirical evidence for urban planning policies.

Hyperuricemia and associated factors among adult cardiovascular disease patients at Salale University Comprehensive Specialized Hospital, Fitche, Central Ethiopia

PLoS ONE Negesse Bokona Rufe, Tolera Ambisa Lamesa, Aklilu Getachew Mamo et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0325775

Background Despite evidence suggesting that hyperuricemia (serum uric acid >7.0 mg/dL in males and >6.0 mg/dL in females) contributes to adverse outcomes like mortality and hospitalization in patients with cardiovascular disease (CVD), a comprehensive understanding of its magnitude is still lacking, underscoring the need for further investigation. There is no previously published study about hyperuricemia in cardiovascular disease in Ethiopia. Therefore, this study aims to investigate the prevalence of hyperuricemia and its associated factors among adult patients with cardiovascular diseases at Salale University Compressive Specialized Hospital Located in Fitche, Ethiopia (115 km north of Addis Ababa),from October 1, 2023, to January 28, 2024. Materials and methods A hospital-based cross-sectional study was conducted on 298 participants with different types of cardiovascular disease. The participants were selected using a consecutive sampling technique. Socio-demographic factors were collected using interviewer-administered questionnaires, while overnight blood samples were collected and biochemical tests were analyzed using the COBAS c 311 automated clinical chemistry analyzer. Descriptive statistics and logistic regression analyses were performed. A variable that had a p-value of ≤ 0.05 with a 95% confidence interval was considered statistically significant. Result The prevalence of hyperuricemia among adult cardiovascular disease patients was 41.3% CI [35.6–47.1]. The highest prevalence of hyperuricemia was found among cardiovascular disease patients with congestive heart failure (48.0%) and hypertensive heart disease (41.2%). Factors such as physical activity (AOR: 4.1; 95% CI: 1.5–10.7, P = 0.004), dyslipidemia (AOR: 2.7; 95% CI: 1.2–6.0, P = 0.01) and chronic kidney disease (AOR: 3.1; 95% CI: 1.5–6.1, P = 0.001) were found to be associated with hyperuricemia among individuals with cardiovascular disease. Conclusion The study indicated a high prevalence of hyperuricemia among participants with cardiovascular disease. Physical activity, dyslipidemia, and chronic kidney disease were recognized as significant associated factors of hyperuricemia among cardiovascular disease. Therefore, early diagnosis of hyperuricemia and its management is essential to control complications and extend the life expectancy of individuals with cardiovascular disease.

Heart failure treatment patterns: A pharmacoepidemiological descriptive study in Colombia (The HEATCO study)

PLoS ONE Manuel E. Machado-Duque, Andrés Gaviria-Mendoza, Luis F. Valladales-Restrepo et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0325515

Introduction Heart failure is a common condition associated with significant mortality. Objective: to determine the prescription patterns of medications for the treatment of heart failure in a cohort of patients from Colombia. Methods This was a retrospective study based on the clinical records of patients diagnosed with heart failure between 2019 and 2020. Sociodemographic, clinical, paraclinical, and pharmacological variables and the specialty of the treating physician were identified. Patients were classified according to functional class, stage, and left ventricular ejection fraction (LVEF). Results A total of 4742 patients were evaluated, with a mean age of 68.2 ± 13.8 years and a male predominance (61.3%). A total of 92.0% were classified as stage C and 54.8% as functional class I, the mean LVEF was 42.9 ± 14.8%, and 32.53% had reduced LVEF. 30.7% did not have LVEF data. The most common causes were ischemic heart disease (44.0%) and arterial hypertension (29.7%). A total of 5.2% had hospitalizations for heart failure in the last year, and 75.6% were attended by a general practitioner. These patients were treated with β-blockers (88.3%), renin-angiotensin-aldosterone system inhibitors (RAASis) (83.1%), loop diuretics (46.8%), and mineralocorticoid receptor antagonists (MRAs) (46.5%). Triple therapy with RAASis + β-blockers+MRAs was received by 56.4% of patients with reduced LVEF, 32.8% with mildly reduced LVEF and19.5% with preserved LVEF, while quadruple therapy adding a sodium-glucose cotransporter-2 inhibitor (SGLT2i) was given just to 4.6% with reduced LVEF. Conclusion The treatment that patients with heart failure with preserved LVEF is relatively simpler and is closer to the recommendations, while the proportion of indicated therapies according to guidelines is lower among those with reduced LVEF.

Organizational barriers in HPV vaccination uptake: A cross-sectional study among health sciences students

PLoS ONE Giuseppina Palena, Irene Stilo, Michele Sorrentino et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0326694

Background Human papillomavirus (HPV) is a leading cause of cervical, anal, and oropharyngeal cancers. Despite the proven effectiveness of HPV vaccination, uptake remains low, particularly among males and specific demographic groups. In Italy, national HPV vaccination coverage stagnated at 38.8% in 2022, with significant regional disparities. While previous studies have explored individual and cultural barriers, organizational challenges within academic institutions remain underexamined. The aim of this cross-sectional study was assessing the uptake of HPV vaccination among Health Sciences students at the University of Naples Federico II. Methods An anonymous online survey collected data on demographics, vaccination status, and institutional barriers. Logistic regression models were used to identify predictors of vaccination, adjusting for demographic factors, institutional communication, and knowledge-attitude scores. Results Among 354 participants, 55.1% reported receiving at least one HPV vaccine dose. Female students had significantly higher vaccination rates (aOR: 7.95; 95% CI: 4.24–14.90), while older age was associated with lower uptake (aOR: 0.81; 95% CI: 0.73–0.91). Institutional vaccination invitations increased the likelihood of vaccination nearly threefold (aOR: 2.81; 95% CI: 1.48–5.33). Attitudes toward vaccination strongly predicted uptake, whereas knowledge scores showed no significant association. Conclusions These findings highlight the need for structured institutional interventions, including targeted education, proactive vaccination invitations, and improved access to on-campus vaccination services. Strengthening university-led initiatives could significantly enhance HPV vaccine uptake among future healthcare professionals, contributing to broader public health efforts in HPV-related cancer prevention.

Feasibility and acceptability of GeneXpert MTB/XDR implementation among healthcare workers in three low-middle income African countries

PLoS ONE Sara Keller, Kogieleum Naidoo, Medhane Zekarias et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0326342

Background Xpert MTB/XDR (Xpert-XDR) testing can significantly shorten time to initiating appropriate drug-resistant tuberculosis (DR-TB) treatment, but its introduction may impact laboratory workflow, especially in laboratories not currently performing drug susceptibility testing. This study evaluated the feasibility and acceptability of implementing the Xpert-XDR for rapid triage and selection of all-oral regimens for DR-TB. Method This was a multi-country, multi-site qualitative study conducted between July and November 2023, as part of the larger TriAD (Triage test for All oral DR TB drugs) study implemented in South Africa, Ethiopia, and Nigeria. We conducted semi-structured in-depth interviews with clinicians, nurses and laboratory staff at each study site until thematic saturation was achieved. Additionally, we interviewed policy makers (n = 9) and people with TB (PWTB) (n = 11), to provide additional insight on the implementation of this new diagnostic assay. Results Healthcare workers (n = 61) found the new workflow feasible and acceptable. It was the increased speed in which PWTB would receive a correct diagnosis and appropriate treatment that provided the biggest benefit to moving to Xpert-XDR for healthcare workers and PWTB. Laboratory staff mentioned that Xpert-XDR had expedited and simplified the laboratory workflows. Role-appropriate and ongoing training is a key factor in effective implementation as described by policy makers and healthcare workers alike. Barriers impacting the ability to perform Xpert-XDR included unstable power supply, internet, and temperature control. Additionally, the Xpert MTB/Rif Ultra test has higher sensitivity for the detection of TB than the Xpert-XDR test, leading to discordant test results. Conclusion This study showed that implementation of Xpert-XDR in health facilities is both feasible and acceptable by all types of healthcare workers. Some barriers with Xpert-XDR are not exclusive to this particular diagnostic tool but are important to address when policy makers are deciding which tools to implement.

Rethinking HIV care for youth: Insights from qualitative research with youth in Chad

PLoS ONE Esias Bedingar, Ferdinan Paningar, Ngarossorang Bedingar et al. Jun 24, 2025 DOI: 10.1371/journal.pone.0309497

Youth ages 15–24 years are significantly impacted by the HIV/AIDS epidemic, representing approximately 37% of new infections globally. This demographic is especially vulnerable in sub-Saharan Africa, where over 80% of HIV-positive youth reside. In Chad, youth face barriers to effective HIV care, including high prevalence rates, particularly among young women, and substantial disparities across regions. Despite overall reductions in new HIV infections, youth remain disproportionately affected, necessitating targeted interventions to improve HIV care outcomes. This study represents a secondary data analysis derived from a parent study that employed a grounded theory design to develop theory inductively. The secondary analysis aimed to generate an in-depth understanding of the pathways to care for youth in Chad, exploring barriers and facilitators across the care continuum, from diagnosis to antiretroviral therapy (ART) adherence. Data were collected through focus group discussions with 52 youth and 48 service providers, including healthcare workers and community actors. Data were transcribed, translated, and analyzed assisted with ATLAS.ti software (Version 7.6.3). Youth identified barriers such as financial constraints, logistical challenges, and fear of stigma, while facilitators included peer support and specialized HIV care facilities. Healthcare workers emphasized the critical role of psychosocial counseling and confidentiality in facilitating youth engagement with HIV services. They also highlighted critical challenges, including the lack of accessible and youth-friendly services, and the need for continuous education to reduce stigma. The findings underscore the importance of tailored, youth-friendly interventions that address these challenges, foster supportive environments, and integrate youth and provider perspectives. We recommend redesigning healthcare services to improve accessibility, reduce stigma, and provide continuous psychosocial support, ultimately enhancing the HIV care continuum for youth in Chad and similar contexts.