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Clinical characteristics, risk factors and outcome of critically ill immunocompromised patients with bloodstream infections and sepsis

PLoS ONE Nirusdee Vonineng, Yuda Sutherasan, Jackrapong Bruminhent Sep 24, 2025 DOI: 10.1371/journal.pone.0332807

Background Immunocompromised patients with sepsis face higher mortality than immunocompetent individuals. However, data on bloodstream infections (BSIs) and sepsis among critically ill immunocompromised (CII) patients remain limited. We aimed to describe the epidemiology, outcomes, and mortality risk factors of BSIs in this population. Methods We conducted a retrospective cohort study of CII patients admitted to the medical ICU between January 2022 and December 2023 with suspected sepsis or septic shock. Patients with BSIs confirmed by positive blood cultures were identified. Propensity score matching (1:1) without replacement was used to create comparable groups for Cox regression analysis of 30-day all-cause mortality. Results Among 211 CII patients (mean age (SD) 61 (16) years, 57% male), 85 (40.3%) had BSIs. The median SOFA and APACHE II scores were 7 (IQR 4–11) and 16 (IQR 14–20), respectively. Immunosuppression was due to hematologic malignancy (37.4%), solid tumors (27.0%), autoimmune diseases (19.0%), solid organ transplantation (5.7%), and other causes (10.4%). Gram-negative rods predominated (65.9%), notably P. aeruginosa (17%), E. coli (17%), and K. pneumoniae (14%). The overall 30-day mortality rate was 48.8%. In the matched cohort (n = 170), higher SOFA scores [HR 1.12; 95% CI, 1.04–1.20; p = 0.003] and lactate >4 mmol/L [HR 1.91; 95% CI, 1.06–3.42; p = 0.031] were associated with increased mortality. Underlying COPD/asthma was associated with lower mortality [HR 0.20; 95% CI, 0.06–0.66; p = 0.009]. Conclusion BSIs are frequent in CII patients and linked to high mortality. Severity of illness and hyperlactatemia predict poor outcomes, while preexisting pulmonary disease may offer a survival benefit.

How labor market institutions influence the relationship between exchange rate regimes and economic growth

PLoS ONE Vytautas Kuokštis, Muhammad Asali, Simonas Algirdas Spurga Sep 24, 2025 DOI: 10.1371/journal.pone.0332492

How do exchange rate regimes affect economic growth? Although this topic has attracted considerable empirical attention, a definitive answer remains elusive. This study aims to advance our understanding by examining how labor market flexibility affects the link between exchange rate regimes and growth. Using a panel of 194 countries from 1970 to 2019, we find that in developing economies, fixed exchange rate regimes hinder growth when labor markets are highly rigid but boost growth when labor markets are highly flexible. We also demonstrate that this relationship varies depending on which labor market flexibility indicator is used, reflecting the differences in each measure’s geographic and temporal coverage.

Tracking the emergence of the Upper Palaeolithic in western Asia and Europe: A Multiple Correspondence Analysis of Protoaurignacian and Southern Ahmarian lithics

PLoS ONE Jacopo Gennai, Armando Falcucci, Vincent Niochet et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0331393

Reconstructing changes in human behaviour during the Pleistocene, particularly when based on lithic or other artefact types, is often hindered by the traditional categorisation of these materials into discrete entities. The Early Upper Palaeolithic of Mediterranean Eurasia – comprising the Protoaurignacian, Early Aurignacian, Northern Ahmarian, and Southern Ahmarian technocomplexes – represents the first emergence of a pan-European cultural unit. However, this conventional categorisation into discrete entities obscures a deeper understanding of the dynamics of Homo sapiens’ dispersal across Eurasia during this period. In this study, we apply Multiple Correspondence Analysis (MCA) to assess patterns of reduction processes, technological variability, and inter-assemblage homogeneity across technocomplexes. Using the comprehensive dataset provided in this paper, we analyse variability by grouping it into three domains: platform preparation, convexity management, and retouch. Solutrean Upper Palaeolithic assemblages from the Iberian Peninsula are used as an outgroup. We selected blanks, retouched and unmodified ones, and we focused on blades and bladelets, which are the typical end-product of the Upper Palaeolithic knapping. We excluded cores to avoid pitfalls of late or early reduction patterns, as our blanks cover most of the knapping sequence. We applied MCA  to Early Upper Palaeolithic blanks for the first time, providing a geographically widespread comparison. Our results show that the MCA of blank attributes, particularly those describing the preparation of convexities, is sufficiently robust to reveal the distinctiveness of Early Upper Palaeolithic technologies relative to Solutrean ones. Our analysis also confirms technological similarities between the Southern Ahmarian and the Protoaurignacian, particularly in bladelet production, reinforcing the interpretation of bladelets as a primary production target in Early Upper Palaeolithic lithic technology. This study contributes laying the foundation for open-access databases, standardised analytical protocols, and MCA to support efforts in understanding hominin dispersal and interaction during this pivotal phase of prehistory.

Long-term conservation agriculture with optimum nitrogen fertilization improves soil phosphorus availability

PLoS ONE Nusrat Jahan Mumu, Sunjana Akter, Afsana Mimi Eiti Mony et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0333013

Understanding the interactive effects of conservation agriculture (CA) and nitrogen (N) fertilization on soil phosphorus (P) dynamics is critical for sustainable nutrient management. However, information on the dynamics and availability of P pools under the combination of long-term CA practices with N fertilization is limited. This study aimed to evaluate the long-term impacts of CA and different N rates on labile, moderately labile, and non-labile P fractions in a wheat (Triticum aestivum)-mungbean (Vigna radiata)-rice (Oryza sativa L) rotation after the 36th consecutive crop. The field experiment was conducted in a split-split plot design with two tillage systems (conventional tillage, CT; strip tillage, ST), two residue levels (lower residue, LR (15 cm); higher residue, HR (30 cm)), and six nitrogen (N) rates (N0, N60, N80, N100, N120, N140 representing 0%, 60%, 80%,100%, 120% and 140%, respectively of the recommended dose). The ST-HR significantly enhanced labile-P availability. Soluble-P, and NaHCO3-Po (organic) increased by 4% and 35% under ST compared to CT, and by 259% and 26% under HR compared to LR, respectively. While HR enhanced most soil P fractions, higher N rates (>N100) tended to decrease labile-Pi (inorganic) fractions by up to 45% suggesting a potential decline in plant-available P. The NaHCO3-Pi was higher in HR coupled with lower N rate (≤N100). Optimum N rate under CA aided in raising the NaHCO3-Po fractions. Moderately labile-P fractions were higher in ST-HR with increased N rate (>N100). Acid-P increased by 38% under ST, with complex interactions observed across treatments. Acid-P was consistently higher in ST-HR coupled with lower N rate (≤N100) while residual-P was higher in ST-LR coupled with same N rate. The interactions among tillage, residue, and N were significant for most P pools highlighting the synergistic effects of CA and N management. Overall, ST-HR-N100 was found to optimize P availability and minimize non-labile P buildup, offering a balanced P dynamics for improved soil fertility and sustainable crop production.

Correlations between social media addiction and anxiety, depression, FoMO, loneliness and self-esteem among students: A systematic review and meta-analysis

PLoS ONE Zhang Jing, Wang Yang, Zhou Lei et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0329466

Background and aims With the ubiquity of the internet, social media have become an essential part of daily life. There are various types of social media, such as Facebook, Twitter, TikTok, WeChat and SNS. Social media addiction (SMA) was found to be significantly associated with mental health concerns, self-esteem, fear of missing out (FoMO), and loneliness on the basis of a literature review concerning SMA. To further explore the connections between SMA and anxiety, depression, self-esteem, FoMO and loneliness, we performed a meta-analysis to quantitatively synthesize the previous findings, Methods The PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Chinese Biological Medicine (CBM) and Technology Journal Database (VIP) databases were accessed to perform a systematic review and meta-analysis. This search was updated in April. Pooled Pearson’s correlation coefficients between SMA and anxiety, depression, loneliness, FoMO and self-esteem were calculated with STATA software via a random or fixed effects model. Results Thirty-two studies involving a total of 26166 students were identified. The meta-analysis revealed positive correlations between SMA and anxiety, depression, loneliness and FoMO (anxiety: summary r = 0.31, 95% CI = 0.25–0.36, P < 0.001; depression: summary r = 0.31, 95% CI = 0.27–0.34, P < 0.001; loneliness: summary r = 0.21, 95% CI = 0.13–0.29, P < 0.001; FoMO: summary r = 0.41, 95% CI = 0.36–0.45, P < 0.001). A negative correlation was found between self-esteem and SMA (self-esteem: summary r = -0.24, 95% Cl = -0.26– -0.22, P<0.001). Conclusions This meta-analysis revealed that SMA was positively associated with anxiety, depression and loneliness but negatively associated with self-esteem. These findings indicate that students with SMA are more likely to suffer from anxiety, depression and loneliness. Conducting larger prospective studies would be beneficial to verify our findings.

Industrial robot application and total factor productivity of manufacturing enterprises

PLoS ONE Minghui Zhao, Zhenhua Wang, Shuangshuang Liu Sep 24, 2025 DOI: 10.1371/journal.pone.0331378

In the context of intensifying global competitiveness and rapid technological advancement, industrial robots have emerged as a pivotal component in the integration of digital technology, exerting a vital influence on the transformation and enhancement of the manufacturing industry. The question of whether this transformative shift can significantly enhance total factor productivity (TFP) and accelerate the transformation of the manufacturing industry has attracted substantial academic attention. This study employs micro-panel data drawn from Chinese A-share listed manufacturing enterprises from 2007 to 2022 to examine the implications of industrial robot application on TFP and the underlying mechanisms. The results of our study indicate that industrial robots have a positive influence on TFP, and this effect persists over time. The results of the mechanism tests indicate that industrial robot application facilitates an increase in human capital, confirming their “talent aggregation effect”. Moreover, the application of industrial robots enhances enterprises’ innovative capabilities, thereby validating their “innovation effect”. Further examination of heterogeneity indicates that the enhancing impact of applying industrial robots on TFP is more pronounced among enterprises with high labor productivity, those that are state-owned, and enterprises operating in high-tech sectors. This research contributes to the understanding of the impact of industrial robot application on TFP, which is of considerable practical significance for emerging economies seeking to transform traditional enterprise factors, accelerate new technology integration, and steer the digital transformation of manufacturing.

Investigating the anti-osteosarcoma effects of Patchouli alcohol through protein network mapping and in vitro experiments

PLoS ONE Zeyu Zhan, He Pang, Hang Wu et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0332202

Osteosarcoma is one of the most common malignant tumors in orthopedics, especially in the metaphysis of tubular bones of the extremities in adolescents. Patchouli alcohol (PA) is a tricyclic sesquiterpene isolated from Patchouli, a Labiatae family, which has been shown to have antitumor efficacy against a variety of cancers. However, the effects and mechanisms of PA against osteosarcoma remain to be elucidated. Sixty-three possible therapeutic targets of PA against osteosarcoma were identified by protein network mapping analysis. PPI network analysis and KEGG functional enrichment analysis showed that PA exerts significant therapeutic effects on osteosarcoma through multiple targets and pathways, especially the PI3K/Akt pathway. Molecular docking results indicated that PA had significant binding to EGFR, HSP90AA1, ESR1 and SRC targets. In vitro experiments, PA inhibited proliferation and induced G2/M arrest in osteosarcoma cells in a dose- and time-dependent manner. PA induced apoptosis in osteosarcoma cells through a decrease in mitochondrial membrane potential. Alterations in the expression of apoptosis-related proteins Bcl-2 and Bax also confirmed that PA promoted apoptosis in osteosarcoma cells. Treatment with PA promoted more autophagosome formation, increased autophagy-related protein LC3-II/I ratio as well as decreased p62 expression in osteosarcoma cells. In addition, PA decreased the expression of p-PI3K/PI3K, and p-Akt/Akt in osteosarcoma cells. These findings indicated that PA exerts anti-osteosarcoma effects by inhibiting osteosarcoma cell proliferation, inducing apoptosis, promoting autophagy and inhibiting PI3K/Akt pathway, suggesting PA as a potential agent against osteosarcoma.

IGF-1 downregulates matrix metalloproteinase 8 to promote plaque stability: Evidence from myeloid cell-specific MMP8 in atherosclerosis

PLoS ONE Patricia Snarski, Sergiy Sukhanov, Tadashi Yoshida et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0332660

Background & aims Macrophages (MF) play an important role in atherosclerosis, a chronic inflammatory disease. Matrix metalloproteinase 8 (MMP8), a collagen degrading enzyme, is expressed by inflammatory cells. Systemic MMP8 deficiency reduces plaque MF and increases collagen suggesting increased plaque stability, however contribution of MF specific MMP8 is unknown. We previously found in Apolipoprotein E-/- mice, Insulin-Like Growth Factor-1 (IGF-1) overexpression in MF reduced MMP8, decreased atherosclerotic plaque MF, and upregulated features of stable atherosclerotic plaque. Thus, we hypothesized that MF specific MMP8 deficiency would reduce plaque burden and promote stability. Methods We used human THP-1 and murine MMP8 deficient MF for in vitro investigation of IGF-1 effect. We generated mice with MF MMP8-deficiency (mM8-:M8 + mice) or MF MMP8-rescue (mM8+ :M8-) by bone marrow transplantation after irradiation; IGF-1 was administered to these and control mice. Results We found IGF-1 reduced MMP8 and suppressed collagenase activity in cultured MF. In Apolipoprotein E-/- mice, MF specific IGF-1 overexpression decreased plaque MMP8 levels and pro-inflammatory cytokines. MMP8 deficient MF had decreased levels of M1 markers and increased expression of M2 markers. We found no difference in atherosclerotic burden between groups, moreover, the ability of IGF-1 to increase collagen production depends on the ability of macrophages to express MMP8. This in vivo effect was only found in females. Conclusions IGF-1 downregulated plaque MMP8 levels in control mice, however this effect was markedly blunted in mM8-:M8 + mice showing that macrophages are the main target of IGF-1 downregulation of plaque MMP8. Overall, our results suggest that macrophage MMP8 may be a potential target to treat unstable atherosclerotic plaques.

Removal efficiency of pharmaceuticals during the wastewater treatment process: Emission and environmental risk assessment

PLoS ONE Paulina Chaber-Jarlachowicz, Barbara Gworek, Radosław Kalinowski Sep 24, 2025 DOI: 10.1371/journal.pone.0331211

The release of pharmaceuticals into the environment is a major concern. These compounds enter waterways through the effluent of wastewater treatment plants (WWTPs). However, most WWTPs using mechanical-biological processes based on activated sludge (CAS) are unable to effectively remove pharmaceuticals. Consequently, pharmaceuticals end up in surface water, seawater and groundwater. While some pharmaceuticals break down or degrade, most remain unchanged and eventually become persistent in the environment, retaining their biological activity even at extremely low concentrations. This study aimed to investigate the occurrence, removal efficiency, environmental discharge and ecological risks of selected pharmaceuticals in municipal WWTPs. Samples were collected from six WWTPs serving over 200,000 people. Concentrations of pharmaceuticals were analysed using the LC-MS/MS method. Removal efficiency was assessed using mass balance calculations for pharmaceuticals in the influent, effluent and sludge. The potential ecological risk posed by individual pharmaceuticals was then evaluated based on the risk quotient (RQ). Concentrations of pharmaceuticals ranged from 7 ng/L to 1,019 ng/L in the influent, from 9 ng/L to 2,266 ng/L in the effluent and from 8.5 μg/kg to 406 μg/kg dw in the sewage sludge. All six WWTPs released pharmaceuticals into the environment. Naproxen, salicylic acid and ketoprofen were the only compounds effectively removed during treatment. Fluoxetine and loratadine posed the greatest risk to aquatic organisms. These findings will lay the groundwork for further research into the inactivation of pharmaceutical active substances and their metabolites in sewage and sludge.

Design and implementation of a Targeted HealthcaRe InnoVation & Entrepreneurship (THRIVE) fellowship program

PLoS ONE Ian C. Odland, Joseph Borrello, Layla Fattah et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0328153

The Targeted HealthcaRe InnoVation & Entrepreneurship (THRIVE) Fellowship was created to bridge the gap between healthcare professionals, who often lack experience in technology development and entrepreneurship, and engineers or technology experts, who may not fully understand clinical needs. This eight-month extracurricular program introduces medical and graduate students to the process of health technology innovation. Fellows form multidisciplinary teams to identify and address an unmet clinical need, following Biodesign principles. The program consists of three phases: (1) introduction to healthcare innovation and foundational skills; (2) team formation, mentor selection, and customer discovery; and (3) solution prototyping, pitching, and business plan development. A retrospective analysis of the 2022–2023 cohort evaluated participant demographics, subjective outcomes (Likert-scale surveys on skill acquisition and program satisfaction), and objective metrics (e.g., milestones completed, funds raised, technology disclosures). Descriptive statistics and paired t-tests for pre-post comparisons were used in the analysis. Of the 56 applicants, 29 were accepted, and 20 completed the program. Fellows rated overall satisfaction at 4.45/5, with 85% planning to incorporate healthcare innovation into their future careers. On average, teams met 10.4 of 12 milestones, raised $10,250 in additional funds (in addition to the $5,000 fellowship grant), and filed multiple technology disclosures. Fellows reported significant gains in key innovation skills (p = 1.3E-5) and spent an average of 7.4 hours per week on their projects. The THRIVE Fellowship fosters interdisciplinary collaboration, practical skill development, and a heightened commitment to healthcare innovation. Early successes include strong participant satisfaction, measurable skill acquisition, and substantial external funding. Future program refinements will focus on expanded mentor engagement, enhanced skill-building resources, and long-term tracking of career outcomes. This model may serve as a scalable approach to training future clinicians and researchers in healthcare technology innovation.

Combined effect of probiotics and omega-3 fatty acids on blood and liver function biomarkers and gut microbiota diversity in male mice with high fat diet-induced obesity

PLoS ONE Kwang Hee Son, Jeongwook Lee, Hee-Young Yang et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0331981

This study investigates the combined effects of probiotics and omega-3 fatty acids on blood and liver function biomarkers, as well as gut microbiota diversity, in a high-fat diet (HFD)-induced obesity model in male mice. Cardiovascular diseases (CVD), often linked to obesity, are major global health issues driven by abnormal cholesterol and triglyceride levels in the blood. Omega-3 fatty acids, known to lower triglycerides and prevent CVD, and probiotics, which enhance gut microbiota balance and nutrient absorption, were evaluated for their combined effects. The experiment involved five groups of male C57BL/6J mice: a normal diet group, an HFD group, an HFD + probiotics group, an HFD + omega-3 group, and an HFD + combined probiotics and omega-3 group. Over six weeks, the combined treatment group showed significant reductions in body weight gain, a significant improvement in ALT levels (a key liver function biomarker), and enhanced anticoagulation markers, such as prothrombin time and activated partial thromboplastin time, compared to the HFD group. Gut microbiota analysis via 16S rRNA sequencing also revealed significant increases in microbial diversity in the combined treatment group. These findings suggest that co-administration of probiotics and omega-3 offers potential therapeutic benefits in reducing obesity-related metabolic dysfunctions by improving lipid metabolism, liver health, and blood circulation.

Nationwide assessment of fall risk and protective factors among older adults in Saudi Arabia

PLoS ONE Ahmad A. Alharbi, Abdulaziz A. Albalwi, Hamad S. Al Amer et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0332900

In Saudi Arabia, nearly half of older adults (49.9%) experience at least one fall annually. Despite its global and regional significance, research on fall risk factors in Saudi Arabia remains limited, with most studies concentrating on specific cities or subpopulations. This study investigated factors associated with falls among older adults across Saudi Arabia. In this cross-sectional study, 473 (58.8% female) older adults (58.4% aged 65–69 years) completed a questionnaire, where we collected data on demographic and health characteristics; additionally, participants completed the Arabic version of the Fall Risk Questionnaire (FRQ-AV). Both descriptive and inferential statistical methods, including logistic regression, were used to analyze the data using SPSS. Based on the FRQ-AV, 168 (35.5%) participants were identified as at risk of falling. After multivariable adjustment, the following significant risk factors were identified: age 70–74 (adjusted odds ratio [aOR]=2.52; 95% confidence interval [CI]: 1.35–4.68; p = 0.004) and ≥80 (aOR=4.85; 95% CI: 1.50–15.63; p = 0.008) years; coexisting diabetes and hypertension (aOR=3.59; 95% CI: 1.75–7.35; p < 0.0005); being somewhat (aOR=4.64; 95% CI: 1.78–12.12; p = 0.002), fairly (aOR=11.36; 95% CI: 4.04–31.91; p < 0.0005), or very afraid of falling (aOR=32.81; 95% CI: 10.88–98.99; p < 0.0005); and falling 1–2 (aOR=5.27; 95% CI: 2.80–9.89; p < 0.0005), 3–4 (aOR=13.06; 95% CI: 5.50–30.98; p < 0.0005), or five (aOR = 12.23; 95% CI: 2.88–51.83; p = 0.001) times in the past year. Protective factors included university education (OR=0.39; 95% CI: 0.22–0.68; p = 0.001) and engagement in physical activity (aOR=0.46; 95% CI: 0.26–0.81; p = 0.007). This study offers significant insights into fall factors and preventive strategies among older adults in Saudi Arabia. This study’s results can help in developing and implementing efficient fall prevention strategies nationwide.

Improving Contraception Outreach through Human-Centered Design: A Pilot Study of the Ndingathe (“I Can”) Intervention in Rural Malawi

PLoS ONE Janelli Vallin, Martha Kamanga, Beth Phillips et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0332149

Background In Malawi, community health workers known as Health Surveillance Assistants (HSAs) can facilitate access to contraception through rural outreach. Self-injectable contraception also shows promise to facilitate contraceptive access, as women can store doses and re-inject on their own. We previously developed the Ndingathe (“I Can”) intervention via human-centered design to strengthen contraception outreach by addressing HSAs’ workflow challenges and enhancing self-injection (SI) counseling and support for interested clients. We piloted Ndingathe in two rural districts from June to December 2023. Methods To assess the feasibility, acceptability, and potential effectiveness of Ndingathe, we conducted: pre- and post-surveys with 60 HSAs; 450 surveys with clients at HSAs’ community outreach clinics; interviews with 40 clients, 20 HSAs, four health system stakeholders, and 20 experienced SI users who supported clients; and 20 observations of outreach clinics. We analyzed quantitative data using descriptive and inferential statistics. We conducted a thematic analysis of qualitative data. Results Intervention components aimed at improving HSAs’ workflow, including bicycles, lunch allowances, and workflow planning templates, were well-received by HSAs and health system stakeholders, and appeared to improve outreach clinic frequency and duration: the percentage of HSAs reporting conducting at least one outreach clinic per week rose from 65% to 95% after the pilot and observations suggested outreach clinic hours extended into the afternoon, instead of ending before lunch, which clients appreciated. HSAs’ average scores on the Role Conflict and Ambiguity in Complex Organizations and Role Overload Scales decreased after six months (2.9 to 2.3, p < 0.0001 and 3.7 to 3.0, p < 0.001, respectively). Both HSAs and clients positively received Ndingathe’s SI mnemonic, designed to aid memory of SI steps, and support from experienced SI users during counseling. Clients’ median self-reported fear of needles decreased from 3 (of 4) to 1 after interacting with an experienced user (p < 0.001). Clients felt reassurance when experienced SI users visited their homes for follow-up visits, conducted without HSAs, to offer support for SI. Challenges during the pilot included delays in lunch allowance disbursement, which impacted HSAs’ morale and ability to expand outreach clinic hours. Conclusion The Ndingathe intervention was feasible and acceptable from the viewpoint of multiple stakeholders in rural Malawi. Pilot findings suggest the intervention has the potential to improve contraception accessibility and reduce fear of self-injectable contraception.

Acceptability of Digital Adherence Technologies to support people with drug-susceptible TB in South Africa

PLoS ONE Tanyaradzwa Nicolette Dube, Fezeka Mboniswa, Liza de Groot et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0332103

Background Tuberculosis (TB) remains a challenge in South Africa, with an estimated 280,000 new cases reported in 2022. Digital Adherence Technologies (DATs) may be important tools to improve adherence to TB treatment. However, there is limited knowledge about facilitators and barriers to implementing these technologies in South Africa. Methods This qualitative study was embedded within the Adherence Support Coalition to End TB cluster-randomised trial which implemented the two technologies: a smart pillbox and/or a cell phone-based strategy similar to 99DOTS (labels), plus differentiated care, to support people with drug-sensitive TB (PWTB). In-depth interviews were conducted with purposively sampled participants comprising PWTB, Healthcare Workers (HCWs) and stakeholders. Inductive thematic analysis was used for data analysis, while the Unified Theory of Acceptance and Use of Technology (UTAUT) framework served as the overarching framework to synthesize and summarise the findings. Findings Sixty-eight interviews were conducted: 35 with PWTB and 33 with HCWs and stakeholders. Facilitating factors for the pillbox were alarm reminder, storage, ease of use, not requiring a phone, social support, and portability. Barriers to the pillbox were that some found the box unportable and others experienced box malfunctioning. Facilitating factors for the labels were ease of use among the young, daily confirmation messages, social support, privacy, and portability. Barriers to implementing these DATs were older age, illiteracy, forgetting to send the SMS, lacking understanding, no cell phone access, power cuts, and unresolvable technical glitches. While differentiated care improved the client-provider relationship, some PWTB felt home visits were stigmatising. HCWs and stakeholders expressed willingness to scale up DATs because they improved their working conditions, and it was advantageous for the PWTB. Conclusions Smart pillbox and labels had features which favoured their acceptability and there were also DAT specific barriers. DATs may improve person-centredness in TB care. Future guidelines should consider acceptability, differing situations, and allowing flexibility to possibly increase uptake and utilisation of DATs.

Voice clones sound realistic but not (yet) hyperrealistic

PLoS ONE Nadine Lavan, Mairi Irvine, Victor Rosi et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0332692

AI-generated voices are increasingly prevalent in our lives, via virtual assistants, automated customer service, and voice-overs. With increased availability and affordability of AI-generated voices, we need to examine how humans perceive them. Recently, an intriguing effect was reported in AI-generated faces, where such face images were perceived as more human than images of real humans – a “hyperrealism effect.” Here, we tested whether a “hyperrealism effect” also exists for AI-generated voices. We investigated the extent to which AI-generated voices sound real to human listeners, and whether listeners can accurately distinguish between human and AI-generated voices. We also examined perceived social trait characteristics (trustworthiness and dominance) of human and AI-generated voices. We tested these questions using AI-generated voices generated with and without a specific human counterpart (i.e., voice clones, and voices generated from the latent space of a large voice model). We find that voice clones can sound as real as human voices, making it difficult for listeners to distinguish between them. However, we did not observe a hyperrealism effect. Both types of AI-generated voices were evaluated as more dominant than human voices, with some AI-generated voices also being perceived as more trustworthy. These findings raise questions for future research: Can hyperrealistic voices be created with more advanced technology, or is the lack of a hyperrealism effect due to differences between voice and face (image) perception? Our findings also highlight the potential for AI-generated voices to misinform and defraud, alongside opportunities to use realistic AI-generated voices for beneficial purposes.

Utilization of psychotropic drugs in Serbia from 2006 to 2021: Patterns before and during the COVID-19 pandemic

PLoS ONE Jelena Filimonovic, Milena Stevanovic, Tatjana Gazibara et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0330749

Background The increasing global prevalence of mental disorders as well as a persistent stigma make mental disorders a public health priority. The aim of this study was to provide a comprehensive overview of psychotropic drugs utilization from 2006 to 2021 in the Republic of Serbia, examining both pre pandemic and pandemic-related changes. Methods To conduct this descriptive study, publicly available data on psychotropic drugs were retrieved from the official website of the Agency for Medicines and Medical Devices of Serbia (ALIMS). The linear and joinpoint regression were used in data analysis. Results A total of 54 psychotropic drugs use was analyzed from 2006 to 2021. There was an increase in the consumption of antidepressants, atypical antipsychotics, anxiolytics, sedatives, hypnotics, anti-dementia drugs and gabapentinoid-based drugs. The increase in the consumption of the psychotropic drugs was linear, with no differences between the pre-COVID-19 period and the COVID-19 pandemic. Contrary, a significant decrease in use was observed for some antidepressants (maprotiline, moclobemide, mianserin), antipsychotics (chlorpromazine, fluphenazine), psychostimulants and nootropic drugs (piracetam), anxiolytics (diazepam, prazepam), sedatives and hypnotics (midazolam). Conclusion The COVID-19 pandemic did not contribute to change in consumption of psychotropic drugs in Serbia. Still, the use of antidepressants, atypical antipsychotics, anxiolytics, sedatives, hypnotics, anti-dementia drugs and gabapentinoids increased from 2006 to 2021.

Misconception about HIV/AIDS transmission among sexually active women in emerging regions of Ethiopia

PLoS ONE Wubshet D. Negash, Tadele Biresaw Belachew, Melak Jejaw et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0331466

Background Misconceptions about how HIV is transmitted persist among sexually active women, especially in emerging regions, and pose a barrier to effective prevention and control efforts. Therefore, this study aims to assess the magnitude of misconceptions about HIV transmission and its associated factors in emerging regions of Ethiopia. Methods This study analyzed secondary data from a community based cross-sectional survey of 497 sexually active women in emerging regions of Ethiopia. Stata version 17.0 was used to analyze the data. Statistical analysis were completed after the data had been weighted. A binary logistic regression model was analyzed. Misconceptions about HIV transmission were addressed by examining whether healthy individuals can have HIV/AIDS and can contract HIV/AIDS through witchcraft, mosquito bites, or sharing AIDS-related foods. Odds ratio along with a 95% confidence interval (CI) was generated to identify factors associated with misconceptions about HIV. A p-value less than 0.05 was declared as statistical significance. Results Overall, 72.71% (95% CI: 68.62–76.46) sexually active women had misconceptions about HIV transmission. Those sexually active women from the poor household’s class (AOR = 2.10; 95% CI: 1.06, 4.13) and those women who had no history of HIV test (AOR = 1.67 95% CI: 1.01, 2.75) were more likely to have misconception about HIV transmission. Conclusion More than seven in ten sexually active women had misconceptions about HIV transmission. HIV prevention initiatives, such as voluntary HIV testing and post-test counseling, are needed to combat misconceptions about HIV transmission. Moreover, the administrative body of each region should facilitate extensive health education and campaigns to increase awareness of HIV transmission among sexually active women, particularly, those from poor households.

An encrypted traffic classification method based on autoencoders and convolutional neural networks

PLoS ONE Shengwei Xu, Jijie Han, Jianbo Wang et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0333276

To solve the problems of existing encrypted traffic classification methods, such as the need for large-scale training data, high computational costs, and poor generalization ability, an encrypted traffic classification method based on autoencoders and convolutional neural networks was proposed. This method first utilizes an autoencoder to recon-struct the dataset, enabling it to work with smaller-scale datasets. The autoencoder allows shorter traffic flows to learn abstract feature representations from longer traffic flows of the same type, replacing zeros and mitigating the negative effects of zero-padding on traffic classification when using uniform flow lengths. After reconstruction, a convolutional neural network is used to classify the traffic. Due to its characteristics of parameter sharing and local connectivity, the CNN exhibits strong generalization ability when handling tasks, allowing it to better adapt to samples outside of the training data. Experimental results show that, compared to existing advanced methods, this method can achieve a classi-fication accuracy improvement of 2.86% to 18.13%, while also demonstrating greater robustness compared to other advanced methods. The code is available at https://github.com/han20011019/AECCN.

The association of POSTN with postoperative recurrence risk in early-stage lung adenocarcinoma: From gene networks to cellular functions

PLoS ONE Youde Xiao, Xuelian Lin, Hui Gong et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0331590

Purpose Periostin (POSTN) has been identified as a biomarker highly correlated with the risk of recurrence of lung adenocarcinoma (LUAD). Increasing the understanding of POSTN’s role in LUAD recurrence may facilitate the development of more effective clinical interventions. Methods Firstly, Weighted Gene Co-expression Network Analysis (WGCNA) analysis was used to identify key genes related to LUAD disease recurrence. Subsequently, the diagnostic performance of these genes was evaluated using Receiver Operating Characteristic (ROC) curves and validated using external datasets. The most effective genes were then analyzed using single- and multivariate Cox regression, linear regression, and stratified analysis to identify their clinical effects. Threshold effect analysis was used to identify the optimal threshold for POSTN expression, and an in vitro experiment was conducted to evaluate the effect of POSTN on tumor cell growth and invasion. Results WGCNA analysis identified four genes strongly associated with LUAD recurrence. POSTN demonstrated good prediction performance for disease recurrence in both The Cancer Genome Atlas (TCGA) and GSE31210 datasets (Area Under the Curve (AUC)=0.693 and 0.743, respectively). Furthermore, POSTN was identified as an independent risk factor for disease recurrence in univariate and multivariate Cox regression analysis, and its expression level was found to be linearly related to disease recurrence in different populations. Threshold effect analysis indicated that a POSTN expression level of 12.5 was associated with a > 50% risk of recurrence within 1 year. In vitro experiments demonstrated that POSTN silencing could inhibit tumor cell proliferation and invasion. Conclusion POSTN is positively correlated with the risk of early LUAD recurrence within 1 year after treatment, indicating its potential as a biomarker for predicting recurrence.

Burden, risk factors, and forecasts of gout in BRICS countries, 1990–2021: Insights from the Global Burden of Disease Study 2021

PLoS ONE Qizhou Mo, Shufeng Luo, Fengyi Wang et al. Sep 24, 2025 DOI: 10.1371/journal.pone.0332265

Objectives To evaluate the temporal trends and projected burden of gout in BRICS (Brazil, Russia, India, China, and South Africa) countries from 1990 to 2021, based on Global Burden of Disease 2021 data, and to explore the contributions of key risk factors. Methods Age-standardized prevalence rates (ASPR), years lived with disability rates (ASYR), and case counts were extracted from the GBD Results Tool. Temporal trends were assessed using estimated annual percentage change (EAPC). Joinpoint regression evaluated time-varying changes in ASYR attributable to high BMI (Body Mass Index) and kidney dysfunction. ARIMA models forecasted ASPR and ASYR through 2036. Results From 1990 to 2021, ASPR and ASYR increased globally and in all BRICS nations. In 2021, China recorded the highest ASPR and ASYR in males (1232.34 and 38.83 per 100,000, respectively), with EAPC of 1.14 and 1.13. Brazil had the lowest burden. In 2021, China and India reported the highest absolute burdens of gout, with approximately 16.79 million prevalent cases and 525,967 YLDs in China, and 5.32 million prevalent cases and 164,153 YLDs in India. High BMI and kidney dysfunction were key contributors to ASYR, especially in older adults. Forecasts indicate ASPR and ASYR will decline globally by 2036, but rise in Brazil, India, Russia, and South Africa. Chinese males show projected declines, while female rates increase modestly. Conclusions The burden of gout is rising across BRICS countries, shaped by aging populations, metabolic risk exposures, and distinct sex-specific trends. These findings highlight the importance of developing locally adapted prevention and control strategies to address this growing challenge.