Search Results (2,685)

Background/Objectives: The factors contributing to residual atherosclerotic cardiovascular disease (ASCVD) risk in individuals are not fully understood, but knowledge of the specific type of dyslipoproteinemia may help further refine risk assessment. We developed a novel phenotyping and risk assessment system that may be applied automatically using standard lipid panel parameters. Methods: NHANES data collected from 37,056 individuals during 1999–2018 were used to develop a three-dimensional dyslipidemia phenotype classification system. ARIC data from 14,632 individuals were used to train and validate the risk model. Three-dimensional Cartesian coordinates were converted to spherical coordinates, which were used as features in a logistic regression model that provides a probability of ASCVD. UK Biobank data from 354,344 individuals were used to further validate and test the model. Results: Nine lipidemia phenotypes were defined based on the concentrations of HDLC, non-HDLC and TG. These phenotypes were related to the prevalence of metabolic syndrome, pooled cohort equation (PCE) score and ASCVD-free survival. A logistic regression model including age, sex and the spherical coordinates of the phenotype provided a composite risk score with predictive accuracy comparable to that of the PCEs. Conclusions: We provided an example of how a multidimensional coordinate system may be used to define a novel lipoprotein phenotyping system to examine disease associations. When applied to an ASCVD risk model, the composite spherical coordinate risk marker, which can be fully automated, provided an F1 performance score almost as good as the PCEs, which requires other risk factors besides lipids. Full article

Hemodialysis (HD) technology, pivotal in managing end-stage kidney disease, has witnessed significant advancements. Yet, the high cost of novel equipment often restricts its usage in resource-limited settings. This study introduces a two-filter adaptation to conventional HD machines, aimed at enhancing toxin removal while maintaining cost-effectiveness. Using a benchtop experimental setup, the performance of the adapted system was compared with that of standard HD. The results demonstrated that the two-filter system improved urea clearance rates by 54% compared with standard HD, without increasing albumin loss or causing additional hemolysis. In a pilot study of four HD patients, the modified setup achieved a higher single-pool Kt/V (1.82) and urea-reduction ratio (80%). These findings underscore the potential of this adaptation to enhance HD machine efficiency without additional patient risks, thereby offering a feasible solution for improving access to advanced renal therapies in under-resourced areas. Further clinical trials with larger populations are warranted to validate these benefits and evaluate middle-molecule clearance for comparison with hemodiafiltration (HDF). Full article

Objectives: An analysis based on epidemiological material to show whether the term Metabolic Syndrome (MS) should be adopted when aiming at predicting coronary heart disease (CHD) and major cardiovascular disease (CVD) fatal events. Material and Methods: MS was defined according to the International Diabetes Federation (IDF) and risk factors were identified in the Italian Risk Factors and Life Expectancy (RIFLE) population study covering over 25,000 adult men from a pool of 19 Italian population samples. The original MS definition and the plain original units of measured risk factors were challenged in Cox proportional hazard models predicting 196 CHD and 412 major CVD fatal events in a seven-year follow-up. Parallel models were run including also total serum cholesterol as a covariate, an unfortunately excluded covariate in the MS definition. The performance of the various models was tested by the log-likelihood statistics treated with the Akaike Information Criterium (AIC). Results: Models using the plain measurements of the risk factors involved were systematically and significantly outperforming any other categorized score based on the IDF-MS classification. An intermediate role was played by a model where the predictive variable was a factor score (derived from a Factor Analysis) where the MS risk factors were linearly combined. The same models also including serum cholesterol provided a significantly better prediction when compared with those without serum cholesterol, based on AIC. Conclusions: The use of a subset of classical CVD risk factors classified according to the IDF-MS criteria adds nothing better than the exclusive use of the risk factors treated by traditional procedures. The addition of serum cholesterol definitely helps in the prediction of the CHD component of major CVD events. Its omission is erroneous. Full article

Zoonotic bacteria, namely Campylobacter spp., Escherichia coli, Salmonella spp. and Staphylococcus aureus, are commonly implicated in human infections and can be transmitted from animals to humans through direct contact, the environment or the food chain. The emergence of antimicrobial resistance in these zoonotic bacteria, namely extended spectrum β-lactamases (ESBLs)-producing strains of E. coli and methicillin-resistant S. aureus (MRSA), has become a public health concern worldwide. This study aimed to determine the prevalence of fecal carriage of Campylobacter spp., Salmonella spp. and ESBL-producing strains of E. coli, as well as nasal carriage of MRSA, and to identify risk factors associated with the presence of these zoonotic bacteria in small ruminants from Portugal’s Central Region. A total of 732 animals, of which 432 sheep and 300 goats from 122 farms were sampled. Zoonotic enteric bacteria were isolated from individual fecal samples, while MRSA were isolated from pooled nasal swabs collected from each farm. Bacteria were isolated according to standard microbiological methods. The overall prevalence of Campylobacter spp. and Salmonella spp. at the animal level was 15.6% and 8.3%, respectively, with significantly higher prevalence in sheep (19.0% and 12.7%) compared to goat (10.7% and 2.0%). Presumptive ESBL-producing strains of E. coli was isolated from 5.2% of the animals. Presumptive MRSA was isolated from 5.7% of the farms. A cluster analysis was performed to identify farm clusters with similar characteristics based on the isolation of Campylobacter spp., Salmonella spp., presumptive ESBL-producing E. coli, and presumptive MRSA. Farms were grouped into three clusters: “Resistant”, “Campylobacter” and “Salmonella”. The likelihood of farms belonging to “Campylobacter” and “Salmonella” clusters in comparison to “Resistant” cluster was associated with animal species, farm location, and farmer’ practices regarding antibiotic use. This study reinforces the role of small ruminants as asymptomatic reservoirs of Campylobacter spp., Salmonella spp., E. coli and S. aureus and confirms, for the first time, their role as carriers of presumptive antibiotic-resistant zoonotic bacteria in Portugal’s Central Region. Full article

Background/Objectives: MOC31 immunostain identifies carcinoma cells and is often used in effusion fluid cytology. This systematic review and meta-analysis aim to detail the diagnostic performance of MOC31 with subgroup analysis for different types of carcinomas. Methods: A literature search from five databases was performed. Relevant studies were reviewed for the calculation of pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve of hierarchical summary receiver operating characteristics (AUC-HSROC). Risk of bias, heterogeneity, and publication bias were assessed by the QUADAS-2, I2 index, and Deeks’ funnel plot. Results: In total, 25 studies (10 retrospective cohorts, 10 case–control studies, and 5 case series) were included. The pooled sensitivity, specificity, NLR, PLR, and DOR were 0.926 (0.827–0.971), 0.932 (0.883–0.961), 0.079 (0.005–0.152), 13.610 (5.327–21.892), and 172.475 (83.150–428.100), respectively. The AUC-HSROC was 0.975, indicating excellent performance. Further analysis for adenocarcinomas, mesotheliomas, and benign/reactive mesothelial cells showed sensitivity for adenocarcinomas at 0.962 (0.948–0.975) and specificity for mesotheliomas and mesothelial cells at 0.934 (0.900–0.967) and 0.997 (0.994–1.000). Sensitivity in all four primary site subgroups (female genital, gastrointestinal/hepatobiliary, lung and breast) of adenocarcinoma were high (>0.910). Heterogeneity was observed, and meta-regression identified a trend for the year of publication. No evidence of publication bias was observed. Conclusions: Evidence shows that MOC31 could be a robust immunocytochemical marker for identifying and excluding metastatic carcinoma, with excellent diagnostic performance across types of adenocarcinomas. However, evidence is mainly from retrospective studies, highlighting the need for high-quality evidence to further establish MOC31diagnostic utility. Full article

Background/Objectives: Artificial intelligence (AI) is entering dental curricula, yet its educational value in endodontics remains unclear. This review synthesized student-based evidence on AI in endodontics, primarily comparing AI vs. students on diagnostic tasks as an educational endpoint and secondarily considering assessment tasks relevant to training. Methods: PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched in July 2025. Eligible studies involved dental students using AI in endodontic tasks or applied AI to student-generated outputs. For diagnostic comparisons we performed random-effects meta-analysis and a complementary Bayesian random-effects model with weakly informative priors. Risk of bias used QUADAS-2; certainty used GRADE. Results: Five studies met inclusion. Two provided complete mean–SD data for the primary meta-analysis and one contributed to a sensitivity model after SD imputation; two were summarized narratively (AUC/F1 only). Pooled effects favored AI: Hedges g = 1.48 (95% CI 0.60–2.36; I² ≈ 84%); sensitivity (k = 3) g = 1.45 (95% CI 0.77–2.14; I² ≈ 77%). Across the two LLM studies with analyzable means/SDs, the pooled mean difference in accuracy was approximately +20 percentage points (AI − students). Bayesian analyses yielded posterior means near 1.5 with 95% credible intervals excluding 0 and P (μ > 0) ≈ 1.00. Educational outcomes were sparsely and non-standardly reported. Conclusions: Student-based evidence indicates that AI likely outperforms dental students on endodontic diagnostic tasks, supporting its use as an adjunct for formative tutoring, objective feedback, and more consistent assessment. Full article

Stingless bee cerumen is a mixture of wax and plant resins. Foragers of stingless bees are exposed to various chemical contaminants during their plant visits and collection activities. These contaminants have the potential to be transferred into the nest. This study aimed to elucidate the existence of chemical contaminants in Ecuadorian cerumen. To this end, the following aims were established: (i) to determine and quantify glyphosate (GLY), aminomethylphosphonic acid (AMPA), some other pesticides, metals and metalloids in cerumen and (ii) to establish possible risks associated with the presence of these chemical contaminants to the health of stingless bees and humans. The quantification of chemical contaminants was conducted using gas chromatography (GC), liquid chromatography (LC), and ion chromatography (IC) coupled to mass spectrometry (MS). Glyphosate (0.02–0.2 mg/kg) and AMPA (0.028 mg/kg) were detected in four of the pooled samples (n = 14) from the northern and southern highland regions. Other pesticide traces were not detected in any cerumen samples. Metals (Cd, Cr, Pb, Ni, Sn) and metalloids (As, Sb, Se) were found in all samples, including highlands and the lower Amazon. The potential risks of exposure to glyphosate and AMPA for stingless bees and humans appear to be minimal (except for the specific conditions given for Tetragonisca angustula) and safe, respectively. It seems that cerumen may serve as an effective biomonitoring matrix for assessing the environmental health of stingless bee nests. Establishing guidelines and regulations for the safe use and handling of products derived from the stingless bee consumption is therefore imperative. Full article

Background: Mitral valve prolapse (MVP) is the most common valvular abnormality in the general population and has been linked to mitral regurgitation, arrhythmias, and sudden cardiac death. Its prevalence and prognostic significance in athletes remain uncertain, raising important questions for pre-participation screening, eligibility for competition, and long-term follow-up. Methods: We systematically searched PubMed, Scopus, and EMBASE databases from inception through August 2025 for original studies reporting MVP prevalence in athletes, diagnosed by echocardiography or pathological assessment. Data on study characteristics, diagnostic definitions, prevalence, arrhythmias, and outcomes were independently extracted by three reviewers. Methodological quality was appraised using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: Twelve studies published between 1987 and 2024 met inclusion criteria, enrolling 19,463 athletes from diverse sports and competitive levels. A total of 407 MVP cases were identified, corresponding to a crude pooled prevalence of 2.4%. Prevalence estimates varied substantially (0.2–20%), reflecting heterogeneity in study populations and diagnostic definitions. When all studies were pooled using a random-effects model, the overall prevalence was 2.0% (95% CI 1.2–2.8%). A sensitivity analysis restricted to contemporary, unselected athletic cohorts yielded a prevalence of 1.1% (95% CI 0.4–1.9%), closely aligning with population-based estimates. Ventricular arrhythmias were more frequent than supraventricular arrhythmias, particularly in association with bileaflet prolapse, leaflet thickening, or significant mitral regurgitation. Most athletes were asymptomatic, and only one prospective study provided long-term follow-up, confirming a generally benign prognosis, though rare adverse events (atrial fibrillation, valve surgery) were documented. Conclusions: MVP is relatively uncommon in athletes and occurs at rates similar to the general population. In most cases, prognosis is favorable and should not preclude sports participation. Nonetheless, recognition of high-risk phenotypes with arrhythmogenic potential highlights the need for individualized evaluation and tailored surveillance strategies in sports cardiology practice. Full article

Background/Objectives: New synthetic opioids (NSOs) like nitazenes pose significant public health risks due to their high potency and increasing prevalence. Ethyleneoxynitazene, a benzofuran-containing nitazene, recently emerged on the illicit market and was identified in seizures in Europe. Although no intoxications have been reported to date, its µ-opioid receptor activity raises concern. This study investigated the metabolism of ethyleneoxynitazene to better understand its pharmacological profile, toxicity, and detectability in clinical and forensic contexts. Methods: Ethyleneoxynitazene was incubated with cryopreserved human hepatocytes pooled from 10 donors. Metabolites were detected by liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-HRMS/MS) and identified using Compound Discoverer (Thermo Scientific; Waltham, MA, USA); detection and identification were assisted by in silico metabolite predictions with BioTransformer. Results: Sixteen metabolites were identified, with major biotransformations including N-deethylation at the N,N-diethylethanamine chain, hydroxylation at the dihydrofuran ring, and dihydrofuran ring opening via oxidative cleavage, leading to the formation of the corresponding ethanoic acid. Conclusions: This study provides the first characterization of the metabolism of a nitazene without an alkoxyphenyl moiety; the absence of this particular group reflects significant differences in the pharmacokinetic and pharmacodynamic profile compared to other nitazenes. We propose N-deethyl-3′-ethanoic acid-4′-hydroxy ethyleneoxynitazene, N-deethyl-hydroxy ethyleneoxynitazene, 3′-ethanoic acid-4′-hydroxy ethyleneoxynitazene, hydroxy ethyleneoxynitazene, and N-deethyl ethyleneoxynitazene as metabolite biomarkers of ethyleneoxynitazene consumption in clinical and forensic toxicology. Given the potential activity of some metabolites and interindividual variability in metabolic pathways, further studies are warranted to refine these findings through the analysis of biological samples from multiple ethyleneoxynitazene-positive cases. Full article

Background: Oncolytic virus (OV) therapy couples direct tumor lysis with systemic immune priming, yet clinical benefit remains heterogeneous and the predictive biomarker landscape is poorly defined. We undertook a systematic review and meta-analysis to quantify the efficacy and safety of OV therapy in solid tumors and to synthesize current evidence on response-modulating biomarkers. Methods: Following PRISMA 2020 guidelines, MEDLINE, Embase, Cochrane CENTRAL, ProQuest and Scopus were searched from inception to May 2025. Phase II–III randomized trials of genetically engineered or naturally occurring OV reporting objective response rate (ORR), progression-free survival (PFS), overall survival (OS) or biomarker data were eligible. Hazard ratios (HRs) or odds ratios (OR) were pooled with random-effects models; heterogeneity was assessed with I² statistics. Qualitative synthesis integrated genomic, immunologic and microbiome biomarkers. Results: Thirty-six trials encompassing around 4190 patients across different tumor types met inclusion criteria. Compared with standard therapy, OV-based regimens significantly improved ORR nearly three-fold (pooled OR = 2.77, 95% CI 1.85–4.16), prolonged PFS by 11% (HR = 0.89, 95% CI 0.80–0.99) and reduced mortality by 16% (OS HR = 0.84, 95% CI 0.72–0.97; I² = 59%). Benefits were most pronounced in melanoma (ORR 26–49%; OS HR 0.57–0.79) and in high-dose vaccinia virus for hepatocellular carcinoma (HR = 0.39). Grade ≥ 3 adverse events were not increased versus control (risk ratio 1.05, 95% CI 0.89–1.24); common toxicities were transient flu-like symptoms and injection-site reactions. Biomarker synthesis revealed that high tumor mutational burden, interferon-pathway loss-of-function mutations, baseline CD8⁺ T-cell infiltration, post-OV upregulation of IFN-γ/PD-L1, and favorable gut microbial signatures correlated with response, whereas intact antiviral signaling, immune-excluded microenvironments and myeloid dominance predicted resistance. Conclusions: OV therapy confers clinically meaningful improvements in tumor response, PFS and OS with a favorable safety profile. Integrating composite genomic–immune–microbiome biomarkers into trial design is critical to refine patient selection and realize precision viro-immunotherapy. Future research should prioritize biomarker-enriched, rational combination strategies to overcome resistance and extend benefit beyond melanoma. Full article

Green hydrogen offers a promising yet underexplored pathway for agricultural decarbonisation, requiring technological readiness and coordinated action from policymakers, industry, and farmers. This paper integrates techno-economic modelling with stakeholder engagement (semi-structured interviews and an expert workshop) to assess its potential. Analyses were conducted for farms of 123 hectares and clusters of 10 farms, complemented by seven interviews and a workshop with nine sector experts. Findings show both opportunities and barriers. While on-farm hydrogen production is technically feasible, it remains economically uncompetitive due to high levelised costs, shaped by seasonal demand variability and low utilisation of electrolysers and storage. Pooling demand across multiple users is essential to improve cost-effectiveness. Stakeholders identified three potential business models: fertiliser production via ammonia synthesis, cooperative-based models, and local refuelling stations. Of these, cooperative hydrogen hubs emerged as the most promising, enabling clusters of farms to jointly invest in renewable-powered electrolysers, storage, and refuelling facilities, thereby reducing costs, extending participation to smaller farms, and mitigating risks through collective investment. By linking techno-economic feasibility with stakeholder perspectives and business model considerations, the results contribute to socio-technical transition theory by showing how technological, institutional, and social factors interact in shaping hydrogen adoption in agriculture. With appropriate policy support, cooperative hubs could lower costs, ease concerns over affordability and complexity, and position hydrogen as a practical driver of agricultural decarbonisation and rural resilience. Full article

Objective: While PARP inhibitors (PARPi) improve progression-free survival (PFS) in advanced ovarian cancer, their efficacy across different surgical outcomes is unclear. We aimed to determine if the efficacy of PARPi maintenance therapy, as measured by PFS, is modified by postoperative residual disease (R0 vs. R1/R2) in newly diagnosed advanced epithelial ovarian cancer. Methods: A systematic review and trial-level meta analysis of randomized controlled trials published through July 2025 was conducted. The primary endpoint was pooled hazard ratio (HR) for PFS, with subgroup analyses based on residual disease (R0 vs. R1/R2), clinical risk (higher risk vs. lower risk), and timing of surgery (primary cytoreductive surgery vs. interval cytoreductive surgery). Results: Six randomized controlled trials involving 3629 patients were included in this meta analysis. PARPi maintenance significantly improved PFS in both patients with no gross residual disease (R0) (HR 0.55, 95% CI 0.44–0.68, I² = 64.2%) and those with macroscopic residual disease (R1/R2) (HR 0.51, 95% CI 0.40–0.65, I² = 56.0%). The treatment effect did not differ significantly between these subgroups (p = 0.66). A numerically greater benefit was observed in lower-risk populations (HR 0.40, 95% CI 0.29–0.55, I² = 0.9%) compared to higher-risk populations (HR 0.51, 95% CI 0.36–0.73, I² = 78.5%, p = 0.30). The benefit was maintained irrespective of surgical timing, with similar pooled HRs for patients undergoing primary (HR 0.56, 95% CI 0.42–0.74, I² = 72.3%) versus interval (HR 0.54, 95% CI 0.45–0.66, I² = 44.2%) cytoreductive surgery. Conclusions: PARP inhibitor maintenance therapy provides a significant PFS benefit regardless of residual disease status, supporting its use in all eligible patients. Complete cytoreduction, however, remains crucial, as it provides the best foundation for achieving optimal long-term outcomes and maximizing the benefits of maintenance therapy. Full article

Background: There is conflicting evidence on whether falling insulin requirements (FIRs) in the third trimester are associated with adverse pregnancy outcomes. We synthesized published evidence to address this knowledge gap. Methods: We conducted a systematic review and meta-analysis, wherein we searched four bibliographic databases until September 04 2025 for articles describing third-trimester FIR and pregnancy outcomes. We assessed the risk of bias using the Quality In Prognosis Studies (QUIPS) tool, performed meta-analysis with pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for maternal and perinatal outcomes and assessed certainty of evidence (CoE) using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: We identified 2044 articles, of which nine fulfilled the eligibility criteria. Third-trimester FIR has an important association with preeclampsia [OR 3.0 (95% CI 1.41–6.38, absolute event rate (AER) 15.9%, high CoE], probably has an important association with neonatal respiratory distress [OR 2.03 (95% CI 1.27–3.26), AER 15.8%, moderate CoE]; may have an important association with a composite of outcomes reflecting placental dysfunction [OR 2.32 (95% CI 1.07–5.03), AER 13.5%, low CoE] and preterm birth [OR 2.0 (95% CI 0.51–7.85), AER 9.3%, very low CoE]; and may not have an important association with stillbirth [OR 1.5 (95% CI 0.27–8.40), AER 0.05%, low CoE], small-for-gestational-age [OR 1.29 (95% CI 0.77–2.15), AER 1.8%, low CoE], or low Apgar score at 5 minutes [OR 1.68 (95% CI 0.68–4.14), AER 2.3%, low CoE]. Conclusions: The CoE regarding associations between third-trimester FIR and adverse pregnancy outcomes varies considerably, and it remains uncertain whether these associations reflect cause or effect. Therefore, a solitary finding of third-trimester FIR does not warrant early delivery and maternal–foetal surveillance should be based on the primary clinical diagnosis. Full article

Background/Objectives: The optimal extent of lateral lymph node dissection in cN1b differentiated thyroid cancer remains controversial. This systematic review aimed to assess the frequency of lymph node involvement across neck levels I to V. Materials and Methods: A systematic review was conducted following PRISMA guidelines. PubMed was searched for studies on lateral neck dissection in differentiated thyroid cancer. Included studies reported level-specified metastatic rates. Data on patient numbers and metastatic events were extracted. A random-effects meta-analysis with Freeman–Tukey double arcsine transformation was performed for each neck level to calculate pooled prevalence proportions and 95% confidence intervals. Heterogeneity was assessed using the I² statistic. Results: Meta-analysis of 57 studies revealed that level III (68%, 95% CI: 63–73) and level IV (66%, 95% CI: 61–70) had the highest metastatic prevalence, followed by level IIA (46%, 95% CI: 37–56). Level V demonstrated an overall prevalence of 22% (95% CI: 18–26), with sublevel VB (19%, 95% CI: 11–28) significantly higher than VA (4%, 95% CI: 1–9). Level I (6%, 95% CI: 2–11) and sublevel IIB (14%, 95% CI: 9–20) showed the lowest risk. Significant heterogeneity (I² 71–94%) was observed across all levels. Conclusions: Our findings support sparing level I, and sublevels IIB and VA during lateral neck dissection. Current guidelines recommend systematic dissection of IIA, III, IV, and VB, although VB involvement was found to be only 19% in our study. Future personalization of the extent of neck dissection, based on individual risk factors, may be key to optimizing oncologic and functional outcomes. Full article

Background/Objectives: Head and neck cutaneous squamous cell carcinoma (HNcSCC) has the potential to metastasize to local lymph nodes, which can significantly impact prognosis. However, the optimal management of patients with clinically node-negative (cN0) disease remains unclear. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. PubMed, Scopus, CINAHL, and Web of Science databases were searched from inception to 7 August 2025. Two parallel searches were conducted: one to capture management strategies and outcomes of cN0 patients with HNcSCC and one to capture occult nodal metastasis rates of the same population. Results: A total of 38 studies were included. Post-excision management strategies included observation, sentinel lymph node biopsy (SLNB), elective dissection (ED), and elective nodal irradiation. The pooled rate of occult lymph node metastasis was 13.9% in 1673 HNcSCC tumors overall and 12.5% when limited to 977 high-risk tumors. Overall recurrence in the SLNB group (8.3%) was significantly lower than both the observation (16.9%, p < 0.0001) and ED (23.7%, p < 0.0001) groups. Additionally, overall mortality in the SLNB group (6.1%) was significantly lower than observation (29.9%, p < 0.0001) and ED (31.4%, p < 0.0001). Conclusions: We found that SLNB was associated with lower recurrence and mortality compared with observation and ED. While not assumed to be causative, our findings support the role of SLNB in diagnosing occult metastasis and staging disease in this population. Full article