Tag: pubmed

Virol J. 2025 Dec 31. doi: 10.1186/s12985-025-03061-6. Online ahead of print.

ABSTRACT

Merkel cell polyomavirus (MCPyV) has been identified as the causative agent of Merkel cell carcinoma, and its non-coding control region (NCCR) has been demonstrated to play a critical role in regulating viral transcription. While NCCR variants exist, their comparative impact on bidirectional promoter activity remains poorly characterized. The present study conducted an in vitro evaluation of bidirectional transcription levels of five major MCPyV NCCR types (I, IIa-1, IIa-2, IIb, IIc). The NCCRs were subsequently cloned into a bidirectional reporter vector, which expresses green (EGFP, early) and red (RFP, late) fluorescent proteins. Subsequent to transfection into HEK293 cells, promoter activity was quantitatively analyzed via fluorescence imaging and flow cytometry. Bioinformatic analysis revealed high sequence similarity (> 94%) among the five NCCRs and predicted conserved transcription factor binding sites. The results indicated that all the variants exhibited stronger late promoter activity compared with the early promoter activity (p < 0.01). These observations are in alignment with the established biology of MCPyV. However, no statistically significant differences in the early/late transcription ratio or overall fluorescence intensity were observed between the different NCCR types under these conditions. These findings suggest that the core promoter function is conserved among these major NCCR variants in this model system. This study provides a foundational comparison of MCPyV NCCR activity, highlighting the need for further investigation in more physiologically relevant models to understand how NCCR diversity may influence viral pathogenesis in vivo. Moreover, incorporating models of viral genome integration is essential to understand mechanism of MCPyV carcinogenesis and viral-host interaction.

PMID:41476298 | DOI:10.1186/s12985-025-03061-6

Eur J Med Res. 2025 Dec 31. doi: 10.1186/s40001-025-03767-x. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare modified transforaminal lumbar interbody fusion (M-TLIF) and posterior lumbar interbody fusion (PLIF) in patients with lumbar degenerative disease complicated by osteoporosis who underwent bone cement-augmented pedicle screw placement, with a focus on lumbar radiographic parameters and clinical outcomes.

METHODS: A retrospective comparative study was conducted on patients with lumbar degenerative disease and osteoporosis who underwent lumbar fusion surgery with bone cement-augmented pedicle screws between January 2021 and June 2023. Based on the surgical procedure received, patients were divided into an M-TLIF group (n = 49) and a PLIF group (n = 44). The comparison encompassed perioperative indicators, radiographic parameters-including the coronal Cobb angle, average surgical segment disc height (ASDH), lumbar lordosis (LL), segmental lordosis (SL), Bridwell fusion grade, and Marchi subsidence grade-and clinical efficacy scores, including the visual analog scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedic Association (JOA) score, which were assessed preoperatively, immediately postoperatively, and at 2-year postoperatively.

RESULTS: The study included 93 patients (M-TLIF: n = 49; PLIF: n = 44). The two groups were comparable in all baseline characteristics (P > 0.05). Regarding perioperative indicators, the M-TLIF group had a significantly longer operative time per segment (185.79 ± 78.46 min vs. 152.92 ± 71.64 min, P = 0.038) but a lower volume of bone cement used per screw (1.86 ± 0.58 ml vs. 2.15 ± 0.62 ml, P = 0.023). Both groups demonstrated significant improvements in all clinical scores (VAS, ODI, JOA) and radiographic parameters (Cobb, ASDH, LL, SL) at all postoperative time points compared to preoperative values (all P < 0.05). At the 2-year postoperatively, VAS and ODI scores were comparable between groups (P > 0.05). Although the JOA score was statistically higher in the PLIF group (25.73 ± 1.26 vs. 25.12 ± 1.51, P = 0.040), the absolute difference of 0.61 points is clinically negligible. Radiographically, the PLIF group achieved a significantly greater SL angle at follow-up (16.59 ± 8.59° vs. 12.17 ± 8.16°, P = 0.013), while the M-TLIF group showed a significantly superior Bridwell fusion grade (P = 0.020). There was no significant intergroup difference in cage subsidence (P > 0.05).

CONCLUSION: Both M-TLIF and PLIF effectively improved the clinical symptoms and radiographic parameters of these patients, with equivalent clinical efficacy in relieving pain and restoring function. The choice of procedure can be individualized: M-TLIF is preferred when superior interbody fusion is the priority, while PLIF is more suitable for achieving greater segmental lordosis.

PMID:41476296 | DOI:10.1186/s40001-025-03767-x

Nature. 2026 Jan;649(8095):73-82. doi: 10.1038/s41586-025-09819-w. Epub 2025 Dec 31.

ABSTRACT

Wearable healthcare electronics are rapidly emerging as a distinct electronics sector in the digital era^1-6, offering substantial economic opportunities and crucial medical benefits. However, their interactions with environmental and social systems remain poorly understood^7-9, leaving critical sustainability challenges unaddressed. Although current efforts have focused on material-level improvements, broader system-level dynamics remain unexplored. Here we present an integrated systems engineering framework based on de novo life-cycle inventories and diffusion-linked scaling to quantify global eco-footprint hotspots and identify effective mitigation strategies. Cradle-to-grave analysis of representative wearable healthcare electronics (glucose, cardiac and blood pressure monitors and diagnostic imagers) generates full-spectrum environmental impact metrics, identifying warming impacts of 1.1-6.1 kgCO₂-equivalent per device. The global device consumption is projected to increase 42-fold by 2050, approaching 2 billion units annually and generating 3.4 MtCO₂-equivalent emissions alongside ecotoxicity and e-waste issues. Contrary to the conventional sustainability emphasis on plastics, this work demonstrates that recyclable or biodegradable plastics offer only marginal benefits, whereas substituting critical-metal conductors and optimizing circuit architectures can significantly reduce impacts without compromising performance. This systems engineering-based life-cycle assessment framework holds promise for establishing ecologically responsible innovation in next-generation wearable electronics.

PMID:41476272 | DOI:10.1038/s41586-025-09819-w

Nature. 2026 Jan;649(8095):83-90. doi: 10.1038/s41586-025-09860-9. Epub 2025 Dec 31.

ABSTRACT

Despite successes in replicating the primary-secondary-tertiary structure hierarchy of protein, it remains elusive to synthetically materialize protein functions that are deeply rooted in their chemical, structural and dynamic heterogeneities^1-12. We propose that for polymers with backbone chemistries different from that of proteins, programming spatial and temporal projections of sidechains at the segmental level can be effective in replicating protein behaviours^13,14; and leveraging the rotational freedom of polymer can mitigate deficiencies in monomeric sequence specificity and achieve behaviour uniformity at the ensemble level^2,3,15-20. Here, guided by the active site analysis of about 1,300 metalloproteins, we design random heteropolymers (RHPs) as enzyme mimics based on one-pot synthesis. We introduce key monomers as the equivalents of the functional residues of protein and statistically modulate the chemical characteristics of key monomer-containing segments, such as segmental hydrophobicity²¹. The resultant RHPs form pseudo-active sites that provide key monomers with protein-like microenvironments, co-localize substrates with catalytic or cofactor-binding sidechains and catalyse reactions such as oxidation and cyclization of citronellal with isopulegol/menthoglycol selectivity. This RHP design led to enzyme-like materials that can retain catalytic activity under non-biological conditions, are compatible with scalable processing and have expanded substrate scope, including environmentally long-lasting antibiotic tetracycline²².

PMID:41476271 | DOI:10.1038/s41586-025-09860-9

Sci Rep. 2025 Dec 31. doi: 10.1038/s41598-025-33124-1. Online ahead of print.

ABSTRACT

The impact of Dexmedetomidine (Dex) use on the prognosis of patients with ventilator-associated pneumonia (VAP) remains a subject worthy of further investigation. This study seeks to evaluate the association between Dex administration and prognosis in critically ill patients with VAP. We conducted a retrospective cohort study using the MIMIC-IV database, including adults (≥ 18 years) with VAP and ICU stays ≥ 24 h. Patients were divided into the DEX group and the non-DEX group based on Dex administration. The primary endpoint was in-hospital mortality, and the secondary endpoint was 90-day survival rate. We used multivariable logistic regression and propensity score matching (PSM) to adjust for baseline imbalances. Kaplan-Meier analysis assessed survival differences. Stratified analyses evaluated temporal trends (2008-2022), dosage (mcg/kg/h), and infusion duration (hours) to further validate the robustness of the results. This research included a total of 1766 VAP patients (DEX: n = 905; non-DEX: n = 861), Dex was associated with reduced in-hospital mortality (unadjusted OR 0.55, 95% CI 0.44-0.69; adjusted OR 0.62, 95% CI 0.47-0.83).The survival curve was calculated based on Kaplan-Meier analysis, which indicated that the DEX group exhibited a relatively longer survival time, and this difference was highly statistically significant (p < 0.001).It is worth mentioning that the mortality reduction remained robust across all sensitivity analyses, including PSM, temporal stratification, and dose-duration subgroups. Dex is associated with significantly lower in-hospital mortality in VAP patients.

PMID:41476257 | DOI:10.1038/s41598-025-33124-1

Eur J Med Res. 2025 Dec 31. doi: 10.1186/s40001-025-03783-x. Online ahead of print.

ABSTRACT

OBJECTIVE: Insulin resistance (IR) plays a critical role in shaping long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Recent findings suggest that biological sex may influence the onset and progression of MASLD, yet it remains unclear whether sex modifies the link between IR and mortality in those with MASLD and advanced liver fibrosis.

METHODS: We analyzed data from 14,081 MASLD patients (7327 men and 6754 women) drawn from the 2001-2018 cycles of the National Health and Nutrition Examination Survey (NHANES). Participants were categorized based on sex-specific deciles of the Metabolic Score for Insulin Resistance (METS-IR). Kaplan-Meier survival analysis and Cox proportional hazards models were used to assess the association between METS-IR and all-cause mortality. Restricted cubic spline (RCS) modeling explored potential non-linear relationships.

RESULTS: Marked sex-related disparities were identified in clinical and metabolic characteristics. Elevated METS-IR significantly predicted increased all-cause mortality in females with MASLD (log-rank p < 0.001), whereas this trend was not evident in males (p = 0.54). Multivariable Cox models showed that higher METS-IR independently correlated with mortality in women with MASLD and advanced fibrosis, but not in their male counterparts.

CONCLUSION: The prognostic significance of METS-IR differs by sex in MASLD. Elevated METS-IR independently increases long-term mortality risk in females, supporting the need for sex-specific risk evaluation in managing metabolic liver disease.

PMID:41476240 | DOI:10.1186/s40001-025-03783-x

Antimicrob Resist Infect Control. 2026 Jan 1. doi: 10.1186/s13756-025-01688-2. Online ahead of print.

ABSTRACT

BACKGROUND: Antimicrobial resistance refers to the ability of microorganisms to become resistant to antibiotics, fungicides, and other antimicrobial agents, which are essential for treating illnesses in humans, land and water-based animals, and plants. This issue is quickly emerging as a major danger to health, economic stability, and livelihoods. One notable driver of these resistant microorganisms is the misuse of antimicrobial medications.

OBJECTIVE: To assess the practices and perspectives on antimicrobial drug misuse in Wolaita Zone, 2024.

METHODS: This study employed a community-based cross-sectional mixed-methods design. The study data were collected from 423 community residents for the quantitative phase and 15 participants for the qualitative phase, data collection for the quantitative component was collected using structured interview-administered questionnaires, and the qualitative component involved in-depth interviews with purposively selected participants, guided by a structured interview. Quantitative data management involved the use of EpiData V4.6 and the Statistical Package for the Social Sciences for data entry and analysis, respectively. The qualitative data underwent thematic analysis utilizing OpenCode software, a qualitative data analysis tool.

RESULTS: In this study, the quantitative data found that 67.1% of participants misused antimicrobial drugs. The factors significantly associated with the misuse of antimicrobial drugs included educational status [AOR: 1.91 (95% CI: 0.93-2.11)], drug cost [AOR: 3.22 (95% CI: 1.18-5.3)], knowledge regarding the use of antimicrobial drugs [AOR: 2.23 (95% CI: 1.66-4.01)], and adherence to stewardship guidelines [AOR: 3.37 (95% CI: 2.44-9.24)]. Additionally, the qualitative study identified four key themes from the data analysis namely, factors related to drug providers, patient-driven factors, sociocultural influences, and limitations in regulatory and policy frameworks.

CONCLUSION: The study reveals a troubling rate of antimicrobial drug misuse among the population. The finding underscores the urgent need to address the gaps and barriers that impede proper use of antimicrobial drugs. It is recommended that government and non-government health sectors, along with relevant stakeholders, implement educational initiatives and health campaigns to combat this problem.

PMID:41476239 | DOI:10.1186/s13756-025-01688-2

Eur J Med Res. 2025 Dec 31. doi: 10.1186/s40001-025-03726-6. Online ahead of print.

ABSTRACT

OBJECTIVES: The study aimed to investigate a non-invasive biomarker for predicting coronary heart disease by analyzing fecal sulfatide levels.

METHODS: A retrospective study was conducted on 593 patients with coronary heart disease, divided into acute myocardial infarction (AMI), unstable angina pectoris (UAP), and stable angina pectoris groups (SAP), and a control group of 200 healthy adults. General information was collected for analysis, and fecal sulfatide levels were compared among groups. Binary logistic regression analysis assessed the correlation between fecal sulfatide levels and coronary heart disease. Statistical analyses were performed to evaluate the risk factors, and predictive value was assessed using receiver operating characteristic (ROC) curves.

RESULTS: Statistically significant differences were observed in the characteristics of age, complete blood cell count, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol between the group of patients with coronary heart disease and the control group (P < 0.05). Noteworthy, fecal sulfatide levels were notably higher in coronary heart disease groups. Furthermore, fecal sulfatide levels in AMI group significantly exceeded those in SAP and UAP groups (P < 0.05). Multivariate logistic regression analysis identified fecal sulfatide as an independent risk factor for coronary heart disease, with an area under the ROC curve of 0.893 (95% CI 0.869, 0.921), indicating strong predictive value.

CONCLUSIONS: Fecal sulfatide may serve as a novel, non-invasive biomarker for early coronary heart disease prediction and risk stratification. However, the retrospective and single-center design of this study limits the generalizability of the results, and future large-scale, multi-center prospective studies are needed to validate these findings.

PMID:41476236 | DOI:10.1186/s40001-025-03726-6

Eur J Med Res. 2025 Dec 31. doi: 10.1186/s40001-025-03603-2. Online ahead of print.

ABSTRACT

OBJECTIVE: This study investigated clinical methodologies for estimating ingested pesticide volume and evaluated their accuracy in acute oral poisonings.

METHODS: The evaluation of poison ingestion was divided into accurate evaluation, empirical evaluation, and simulated ingestion evaluation. Statistical analysis was conducted using the data of 60 cases of acute oral paraquat poisonings (PQP) in our hospital from the aspect of empirical evaluation, simulated ingestion evaluation, blood toxicant test, and prognosis. Moreover, the measurements of oral capacity and simulated dose were compared in the general population based on sex, age, height, weight, and season.

RESULTS: A significant difference was observed between the amount based on empirical evaluation and that based on simulated ingestion evaluation (P < 0.05). In simulated ingestion evaluation, the amount in males was significantly higher than that in females, and the amount in males was correlated with blood toxicant concentration and prognosis. No statistical difference in oral capacity was observed in the general population based on age, season, and body weight (P > 0.05). Both the maximum and normal mouthfuls in males were statistically different from those in females (P < 0.05, P < 0.05). A statistical difference in oral capacity (maximum mouthful and normal mouthful) was observed among various height groups (P < 0.01, P < 0.05), indicating that the higher the height, the larger the oral capacity.

CONCLUSIONS: Only 7.69% of the cases were allowed for an accurate dose evaluation. The ingested poison dose based on empirical and simulated ingestion evaluation were correlated with blood toxicant concentrations and prognosis in patients with PQP. Factors, such as sex and height, should be considered by physicians in empirical evaluation. It is still a great clinical challenge to accurately evaluate the ingested dose of liquid pesticides.

PMID:41476215 | DOI:10.1186/s40001-025-03603-2

Trop Med Health. 2025 Dec 31;53(1):198. doi: 10.1186/s41182-025-00893-4.

ABSTRACT

INTRODUCTION: Hepatitis B virus (HBV) infection remains a significant global health threat, with over 296 million individuals living with chronic HBV and more than 820,000 annual deaths due to related complications. Healthcare workers (HCWs) are at heightened risk due to occupational exposure, especially in sub-Saharan Africa, where HBV prevalence and health system limitations compound their vulnerability. Despite the availability of an effective vaccine, adherence to the three-dose HBV vaccination schedule among HCWs in Nigeria remains suboptimal. This study seeks to explore the psychosocial and digital factors influencing non-adherence to the HBV vaccination schedule among HCWs in Nigeria, with the aim of informing more targeted and effective interventions.

METHODOLOGY: A cross-sectional survey was conducted among 530 healthcare workers at FMC Keffi to assess Hepatitis B vaccine uptake and its determinants. Data were collected using a structured, pre-validated questionnaire covering vaccination status, knowledge, attitudes, barriers, and digital access. Statistical analyses included descriptive statistics, Chi-square tests, binary logistic regression, mediation (PROCESS Model 4), and moderation analyses. These methods evaluated the direct and indirect effects of knowledge, attitudes, occupational exposure, and digital intervention beliefs on vaccine adherence, with gender assessed as a moderating variable.

RESULTS AND DISCUSSION: Among 530 healthcare workers at FMC Keffi, only 19.4% were fully vaccinated against Hepatitis B, while 72.6% had received at least two doses. Mediation analysis showed that knowledge had no significant direct or indirect effect on vaccine uptake (p = 0.21), whereas attitude was a strong predictor (B = – 9.85, p < 0.001). Occupational exposure significantly influenced adherence (χ2 = 33.00, p < 0.001), as none of the unexposed were fully vaccinated. Gender moderated the attitude-uptake link, with females showing stronger associations. Digital access remained low, limiting the effectiveness of digital intervention strategies.

CONCLUSION: This study concludes that HBV vaccine adherence among healthcare workers is influenced more by attitudinal factors, occupational exposure, and gender dynamics than by knowledge alone. Digital intervention strategies remain underutilized due to limited access. To improve vaccine uptake, health systems must adopt multifaceted approaches that prioritize behavioral insights, gender sensitivity, and equitable access to digital health resources.

PMID:41476203 | DOI:10.1186/s41182-025-00893-4