The rise in global restrictions on antibiotic growth promoters have intensified the search for sustainable and safe alternatives. Phytogenic feed additives (PFAs) have emerged as promising contestants because of their diverse biological properties. This research studied the potential effects of herbal extracts as the standardized PFA containing tannic acids derived from Chinese gallnuts on intestinal morphometry, growth performance and cecal microbiota. For this purpose, 224 one-day-old male Ross 308 broiler chicks were allocated to 28 cages, with eight birds per cage and seven replicate cages per treatment, in a 35-day trial. The four dietary treatments were: negative control (NC) without antibiotic growth promoters, NC + avilamycin at 100 g/t, NC + colistin sulfate at 100 g/t, and NC + Chinese gallnuts tannic acids (CGTA) at 200 g/t. The growth performance indices were observed during the whole production cycle. The intestinal morphometry was observed on the day 35. The dietary inclusion of CGTA significantly improved feed conversion ratio (FCR) during 0 to 10 and 0 to 21 days as compared to NC diet treatment. Moreover, the European Production Efficiency Factor (EPEF) of 441 was also observed numerically higher in the CGTA supplementation treatment. Additionally, the intestinal morphometric analysis revealed a substantial rise in both the duodenal and jejunum height of villus and a decrease in epithelial thickness in both duodenum and jejunum, indicating the enhanced absorptive capacity and gut integrity. Crypt depth and goblet cell numbers were not affected significantly. Notably, microbiota analysis showed no significant differences in alpha or beta diversity. In conclusion, dietary supplementation of CGTA at 200 g/t improved feed efficiency and intestinal morphometry in broilers, without altering the community of cecal microbiota.
Loot boxes are virtual chests containing randomized in-game items. Given their structural similarities, loot boxes have been argued to be a form of gambling. Indeed, previous meta-analytic studies suggest that loot boxes are associated with problem gambling severity and act as a "gateway" to gambling. Yet, little is known about loot box purchasing among individuals who already gamble. In the present study, we assessed the demographic characteristics and addictions and mental health comorbidities of adult loot box purchasers, through a nationally stratified sample of regular gamblers who also regularly play video games (N = 3709). We also investigated whether loot box engagement is associated with problem gambling severity and gambling harms when controlling for traditional gambling activities. Of the total sample, 1,922 reported having purchased loot boxes (Mage = 38.72, 61.3% male). Loot box purchasers were more likely to be younger, single, employed, have a college degree or higher, and report upper-middle income. Loot box purchasers were significantly more likely to endorse addictions and mental health comorbidities (e.g., substance use, depression). When controlling for other forms of gambling (e.g., electronic gambling machines, sports betting), both the frequency of loot box purchasing and money spent were associated with problem gambling severity and gambling-related harms. The results from the present study provide further support that loot boxes when purchased with money may be conceptualized as a form of gambling and contribute to problem gambling risk and harms. Given the popularity of loot boxes and relative lack of age restrictions, jurisdictions may wish to regulate the purchase of loot boxes similarly to traditional forms of gambling.
Nonpharmacological therapies are widely used for adult myogenic temporomandibular disorders (TMD), but their comparative effectiveness for pain and mandibular function remains uncertain. This study compared multiple interventions using a frequentist random-effects network meta-analysis. MEDLINE (via PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and Google Scholar were searched from inception through October 31, 2025, without language restrictions. Randomized controlled trials enrolling adults (≥ 18 years) with myogenic TMD were included if they compared at least one predefined nonpharmacological modality (including photobiomodulation therapy [PBMT], manual therapy [MT], exercise therapy [EX], occlusal splint therapy [OST], acupuncture [ACU], electrotherapy [ELEC], combined therapy [COMB], cognitive behavioral therapy [CBT], central neuromodulation, or extracorporeal shock wave therapy) with sham or placebo control, usual care or no-treatment control, or another predefined active nonpharmacological modality. Primary outcomes were pain and maximum mouth opening, and outcome data were extracted at the short-term assessment closest to completion of the intervention. Effects were summarized as standardized mean differences (SMDs) with 95% confidence intervals (CIs) using a frequentist random-effects model implemented in Stata. Treatments were ranked using the surface under the cumulative ranking curve (SUCRA), which provides a probabilistic ranking rather than a direct measure of treatment superiority. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool (RoB 2.0). Forty-one trials (2021 participants) were included. For pain, PBMT ranked highest (SUCRA, 88.9%) and was superior to CBT (SMD, - 2.00; 95% CI, - 2.99 to - 1.00), ELEC (SMD, - 1.64; 95% CI, - 2.55 to - 0.73), conventional care (SMD, - 1.49; 95% CI, - 2.07 to - 0.91), OST (SMD, - 1.43; 95% CI, - 2.29 to - 0.56), and ACU (SMD, - 1.07; 95% CI, - 1.93 to - 0.21). MT (SUCRA, 79.9%) and COMB (SUCRA, 72.5%) also showed significant analgesic advantages versus several comparators. For maximum mouth opening (31 trials; 1463 participants), MT ranked highest (SUCRA, 92.9%) and improved opening more than conventional care (SMD, 2.79; 95% CI, 1.33 to 4.26), PBMT (SMD, 2.23; 95% CI, 0.19 to 4.28), ACU (SMD, 2.01; 95% CI, 0.12 to 3.90), and EX (SMD, 1.85; 95% CI, 0.05 to 3.64). Inconsistency was detected for pain in the ELEC versus MT comparison; no significant inconsistency was observed for maximum mouth opening. Among adults with myogenic TMD, PBMT showed the most favorable short-term comparative profile for pain relief, whereas MT ranked highest for improving maximum mouth opening. These findings support targeted selection of specific nonpharmacological modalities, prioritizing PBMT when pain reduction predominates and MT when restoration of mandibular mobility is the primary goal. PROSPERO (CRD420261278458).
As adolescents grow older, they increasingly engage with the food environment. Our study aimed to: 1) assess the contribution of prepared out of home (POH) foods to the healthiness of adolescent diets and 2) identify socio-demographic factors associated with POH foods intake in a rural, a peri-urban, and an urban area of Vietnam. We conducted a cross-sectional survey among 11-19-year-old adolescents (n = 2,861) and collected socio-demographic and dietary intake data (24-hour recall). The healthiness and micronutrient adequacy of diets was assessed using the Global Diet Quality Score (GDQS) and the micronutrient adequacy ratio (MAR) respectively. We used regression analyses with robust standard errors (to account for school-level clustering) to assess the consequences and identify the drivers of POH food intake. Over 80% of adolescents consumed foods POH on the previous day, contributing 22-26% of daily energy intake. Healthy food groups were underrepresented in POH foods, which were higher in fat, saturated fat, and sodium, but also had higher micronutrient density than foods prepared at home. POH intake was associated with higher energy intake and micronutrient adequacy, but lower diet healthiness. Socioeconomic status, female sex, pocket money, and smartphone ownership were associated with POH consumption, with site-specific differences. Food environments should be made healthier through front-of-package warning labels, reformulation (e.g., reducing milk fat and sugar), and restrictions on the marketing and availability of unhealthy foods combined with the promotion of healthy foods, snacks and meals.
In 2023, a majority (86%) of open-heart surgeries was performed at Thorax Centrum Twente (TCT) via a full median sternotomy. Currently, there is no consensus on postoperative sternal precautions following full median sternotomy. Research from the USA and Canada suggests that existing restrictive sternal precautions may not be necessary. More lenient sternal precautions, such as the "Keep Your Move in the Tube" principle, have shown positive outcomes, with no significant complications. Patients following this approach experienced fewer mobility issues and reported improved quality of life and reduced anxiety. This study explores the potential benefits of fewer restrictions, which could reduce patient anxiety and lead to fewer follow-up visits. This study aims to determine whether the Thoracic Surgical Rehabilitation Experts Twente (T-REX Twente) sternal precautions have a small positive effect on the Modified MacNew Quality of Life after Myocardial Infarction questionnaire (QLMI-2), physical activity, and reduction of movement-related anxiety in patients after full median sternotomy, compared to standard restrictive sternal precautions. It also assesses whether the T-REX sternal precautions result in no negative effects on pain, wound healing, or postoperative complications. This prospective, randomized, controlled, single-blind study will include adult patients undergoing full median sternotomy at TCT between June 2024 and June 2026, all participating in outpatient cardiac rehabilitation. Exclusion criteria include intensive care unit stays over 72 h, delirium, dementia, severe cognitive impairments, language barriers, or treatment by an external referring cardiologist. The control group will adhere to current restrictive sternal precautions, whereas those in the intervention group will follow the T-REX sternal precautions, which allow lifting, pushing, or pulling as long as arm movement remains within a defined "tube." The primary endpoint is the change in QLMI-2 from baseline (T0) to start of phase II cardiac rehabilitation (T4). The T-REX Twente sternal precautions may improve quality of life, physical activity, and reduce movement-related anxiety, supporting the idea that less restrictive postoperative sternal precautions can enhance patient outcomes. CCMO Trial Register NL78107.100.23, registered on 29 February 2024. gov: NCT06115759.
A potential interaction between citrate and lactate metabolism may exist in critically ill patients receiving continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA). Although prior studies have investigated the relationships of initial lactate levels and lactate kinetics with citrate accumulation and clinical outcomes, the prognostic significance of lactate kinetics during RCA-CRRT remains inadequately defined. Critically ill patients undergoing CRRT (CRRT cohort) and those receiving RCA (Lactate Kinetics cohort) were identified from the MIMIC-Ⅳ (v3.1) database, as well as from the MIMIC-Ⅲ (v1.4) database (Lactate Kinetics Validation cohort). Propensity score matching, Kaplan-Meier survival curves, and Cox regression models were employed to assess the association between RCA use and 7-day and 28-day all-cause mortality. Latent growth mixture models, receiver operating characteristic curves, and restricted cubic splines were applied to identify lactate kinetics during RCA-CRRT. The association between lactate kinetics and mortality was evaluated using Kaplan-Meier survival curves and Cox regression models. LASSO-logistic regression analysis was applied to identify clinical characteristics associated with lactate kinetics. A total of 1,952, 1,064, and 209 patients were included in the CRRT cohort, Lactate Kinetics cohort, and Lactate Kinetics Validation cohort, respectively. The adjusted 7-day all-cause mortality risk was lower in patients who received RCA compared to those who did not, whereas no significant association was observed for 28-day mortality risk. Four distinct lactate trajectories during RCA-CRRT were identified: Class 1, low lactate with a stable trend; Class 2, high lactate with an improving trend; Classes 3-4, moderate lactate with gradually or rapidly worsening trends. Patients in Classes 3-4 exhibited significantly higher 7-day and 28-day mortality risks compared with Class 1, whereas Classes 2 showed no significant difference. SOFA score, respiratory failure, baseline lactate level, and mean daily citrate consumption were associated with an increased risk of lactate worsening, whereas pH and total carbon dioxide levels were associated with a decreased risk of lactate worsening. Patients with an increase in lactate greater than 1 mmol/L had significantly higher 7-day and 28-day mortality risks compared to those with an increase of less than or equal to 1 mmol/L. Although RCA may not increase overall mortality risk in critically ill patients, lactate worsening during RCA-CRRT has been observed and is strongly associated with adverse outcomes in certain patient populations. Timely clinical evaluation and individualized treatment adjustments are appropriate for these patients.
Multiple sclerosis (MS) is a significant cause of neurological disability in young adults. Siponimod, a potent sphingosine-1-phosphate (S1P) receptor modulator, is used to treat MS by reducing T-cell recirculation and central inflammation. The presented work includes clinical data describing the impact of the CYP3A4 inhibitor clarithromycin on siponimod metabolism and the results of updated physiologically based pharmacokinetic (PBPK) modeling. A clinical drug-drug interaction (DDI) study assessed the effect of clarithromycin on siponimod pharmacokinetics in healthy participants with the CYP2C9*1*3 genotype. Results revealed minimal differences in PK: a 2% increase in Cmax, an 8% increase in AUClast and a 9% increase in AUCinf, confirming no clinically relevant drug-drug interaction (DDI). The existing siponimod PBPK model was updated using these DDI study data, estimating a CYP3A4 fraction metabolized of 6.4% in the CYP2C9*1*1 genotype. Simulations using the updated PBPK model in the absence and presence of the restricted co-medication (CYP2C9 and CYP3A perpetrators) were conducted. There was no clinically relevant DDI with moderate and strong CYP3A4 inhibitors across CYP2C9 genotypes with a predicted maximum net AUC increase of 1.33. Co-administration of fluconazole, a moderate CYP3A4 and CYP2C9 inhibitor, was predicted to result in < 2-fold net AUC increase, except for the genotype CYP2C9*2*2, where a 2.2-fold net AUC increase compared to the CYP2C9 wild type without fluconazole co-treatment was observed. Siponimod Cmax and AUC were comparable across CYP2C9 genotypes during dose titration in the absence or presence of fluconazole, suggesting no impact on the effectiveness of the dose titration regimen.
Research misconduct poses a serious threat to academic integrity, particularly in medical sciences. This study aimed to estimate the prevalence of various forms of research misconduct include plagiarism, data fabrication or falsification, authorship misconduct, salami slicing, and purchasing research work among postgraduate students in Iranian medical universities using the Unmatched Count Technique (UCT). A cross-sectional survey was conducted among postgraduate students from multiple Iranian medical universities using a double-list version of the unmatched count technique (UCT). The questionnaire was administered in two sequential waves, with approximately half of participants completing List A and the remaining participants completing List B, ensuring that each respondent received only one list version. For each research misconduct behavior, prevalence was estimated by calculating the mean difference in endorsement counts between lists containing the sensitive item and corresponding control lists with only non-sensitive items. In the double-list design, prevalence estimates were computed separately for List A and List B, with sensitive items counterbalanced across list positions to control for order effects. The final prevalence was calculated as the average of the two list-specific estimates, improving precision and reducing list-order bias. The most commonly reported misconduct was using others' ideas or phrases without proper citation (43%), followed by dishonest result reporting (38%), data fabrication or deletion (34%), and authorship misrepresentation (34%). Salami slicing was reported by 26%, and 20% admitted to purchasing parts or all of a research project. The UCT survey tool demonstrated acceptable reliability, with intraclass correlation coefficients (ICCs) ranging from 0.64 to 0.84. The findings indicate a troubling level of research misconduct among postgraduatestudents in Iran's medical sciences universities. This highlights the need for effective ethics training, stronger academic integrity policies, and enforceable institutional mechanisms to promote responsible research conduct and protect the future credibility of medical professionals.
Solar hydrogen production using photoelectrochemical (PEC) water splitting is an efficient method for mitigating energy issues and adverse environmental impacts. BiVO4 is a highly promising photocatalytic material for PEC water oxidation because it features appropriate bandgap and advantageous band-edge locations. However, the restricted hole diffusion length and surface electron-hole recombination in BiVO4 result in a sluggish water-splitting process. To address the existing shortcomings, a highly effective W-BiVO4/H/NiCo-layered double hydroxide (LDH) photoanode is designed through W doping, hydrogen treatment, and NiCo-LDH modification of BiVO4 in this study. W-BiVO4/H/NiCo-LDH exhibited considerably higher photocurrents, 5.89 and 1.64 times higher than those of BiVO4 and W-BiVO4/H at 1.23 V vs. RHE, with negatively shifted onset potentials of 270 and 170 mV, respectively. The maximum applied bias photo-to-current conversion efficiency of W-BiVO4/H/ NiCo-LDH is 6.5 and 2.5 times higher than those of BiVO4 and H/W-BiVO4, respectively. Furthermore, the photoanode exhibits high surface charge injection efficiency of ∼74% and exceptional stability holding ∼91% of its initial photocurrent density after 7200 s of continuous PEC reaction. This enhancement can be attributed to three factors: (i) W doping, which enhances PEC performance through n-type doping by substituting V5+ sites with higher-valence W6+ ions, increasing donor density and electrical conductivity; (ii) subsequent hydrogen treatment, which creates oxygen vacancies that facilitate charge separation, increase the carrier concentration, and reduce the bulk charge recombination; and (iii) the NiCo-LDH layer facilitating efficient hole extraction and accelerating interfacial charge injection for the oxygen evolution reaction.
Monitoring exercise intensity is essential for optimizing the health benefits of physical activity. Indirect calorimetry is the gold-standard method for assessing metabolic stress during exercise, though, its reliance on extensive equipment for sampling and analyzing exhaled gases restricts its widespread application. Skin interstitial fluid may represent an ideal biofluid for the continuous monitoring of whole-body metabolism and exercise intensity. However, specific metabolites in skin interstitial fluid that are more closely associated with metabolic variables measured by indirect calorimetry remain unknown. We examined which metabolites in skin interstitial fluid most closely reflect metabolic responses assessed by indirect calorimetry during a continuous graded exercise protocol. Twelve young participants (5 females) exercised at low, moderate, and high-intensity phases (25%, 50%, and 75% VO₂peak), each lasting 20 min. Skin dialysate, which reflects the composition of skin interstitial fluid, were collected via intradermal microdialysis during each exercise, and metabolites in the dialysate were measured and analyzed. Medium- and long-chain acylcarnitines in skin dialysate increased during moderate-intensity exercise in line with elevations in whole-body fat oxidation. During high-intensity phase, lactic acid in skin dialysate was elevated along with increases in whole-body carbohydrate oxidation. Many metabolites including those mentioned above in skin dialysate were correlated with whole-body metabolic responses. Our preliminary data suggest that metabolite concentrations in skin interstitial fluid may be associated with variables measured by indirect calorimetry. These findings may inform the future development of wearable devices that could potentially be used for continuous and noninvasive monitoring of exercise intensity.
Metabolic dysfunction-associated steatotic liver disease (MASLD) significantly exacerbates the prognosis of patients with type 2 diabetes mellitus (T2DM). We aimed to compare metabolic and adiposity-related surrogates for MASLD using data-driven feature selection and to validate a parsimonious risk model across distinct populations. We included 449 T2DM patients from the WMU cohort (discovery) and 306 from the Japanese NAGALA cohort (external validation). A two-stage data-driven feature-selection framework (Boruta and LASSO) was implemented to identify a parsimonious two-variable signature (TyG-BMI and SGLT2i). Based on these results, TyG-BMI was prioritized for systematic evaluation. Association and dose-response relationships were assessed via multivariate logistic regression and restricted cubic splines. Multiplicative and additive interactions between TyG-BMI and LDL-C were further explored. Clinical utility was evaluated via AUC, NRI, IDI, and decision curve analysis. The Boruta algorithm ranked TyG-BMI as the feature with the highest importance score for MASLD classification. Subsequently, LASSO regression (utilizing the 1-standard-error criterion λ1se) identified a parsimonious two-variable signature comprising TyG-BMI and SGLT2i. In the WMU cohort, TyG-BMI exhibited a potent association with MASLD (T3 vs. T1: OR = 7.36, 95% CI 3.89-13.94) and a significant linear dose-response relationship (P for overall < 0.001). Incorporation of TyG-BMI into the baseline model improved discriminative performance (AUC increased from 0.7288 to 0.7920) and was associated with improved continuous reclassification (NRI: 0.6088, P < 0.001). DCA and calibration plots confirmed high clinical net benefit and accuracy. Furthermore, a significant synergistic interaction was observed between TyG-BMI and low-density lipoprotein cholesterol (LDL-C). TyG-BMI, selected through data-driven feature selection, may serve as a practical candidate predictor of MASLD in patients with T2DM. The observed interaction between TyG-BMI and LDL-C suggests that their joint assessment may further refine MASLD risk stratification. The derived parsimonious model offers a high-performing, non-invasive tool for early MASLD risk stratification across Asian populations.
The pronounced genetic heterogeneity of Botrytis cinerea confers adaptive advantages in fluctuating environments.  Consequently, elucidating the pathogen's population structure within agricultural ecosystems is essential for developing enhanced control strategies. A total of 171 Botrytis isolates were collected from greenhouse-grown tomatoes in Liaoning province, China. Through integrated morphological characterization, restriction fragment length polymorphism analysis of the Bc-hch gene, and multi-locus phylogenetic analysis based on G3PDH, HSP60 and RPB2 sequences, the dominant species responsible for tomato gray mold in Liaoning was identified as B. cinerea. The diversity of B. cinerea isolates was assessed by characterizing transposable elements (TEs) including Boty and Flipper, determining mating types (MAT1-1 and MAT1-2), and conducting morphological and microsatellite (SSR) analyses. Based on TEs profiling, the isolates were classified into three types: Boty, Flipper, and Transposa, accounting for 19.3%, 25.7%, and 55.0% of the population, respectively. The composition of TE types differed significantly among sub-populations. The overall ratio of MAT1-1 to MAT1-2 deviated from 1:1. However, in 13 out of 14 geographic sub-populations, the mating type ratio was consistent with 1:1; only one sub-population exhibited a significant deviation. Genetic diversity was evaluated using nine SSR markers, revealing a high level of polymorphism. Most genetic variation was observed within populations. A moderate level of gene flow was detected among populations, along with a relatively high inbreeding coefficient. Significant genetic differentiation was observed among geographical populations, with the highest diversity found in Anshan and Fuxin, and the lowest in Huludao. Cluster analysis indicated a discernible phylogeographic pattern, suggesting an association between genetic relationship and geographic distance. The findings of this study enhance our understanding of the population structure and genetic diversity of B. cinerea in Liaoning province, providing valuable insights for disease management strategies.
The inherent recalcitrance of lignocellulosic biomass, primarily attributed to the dense lignin-carbohydrate complex (LCC), restricts the efficient valorization of plant fibers. Conventional alkaline degumming strategies suffer from high energy consumption, severe pollution, and non-selective cellulose degradation. Herein, a mild, alkali-free pretreatment strategy was developed using a visible-light-driven g-C3N4/TiO2 heterojunction to achieve efficient and selective delignification of hemp fibers. Under ambient conditions (30 °C, neutral pH), the system achieved a delignification efficiency of 69.08 % while preserving the cellulose crystallinity (CrI increased to 78.64 %). Crucially, 2D-HSQC NMR and EPR analyses revealed a selective oxidative mechanism: photogenerated superoxide radicals (•O2-) acted as specific nucleophiles, preferentially cleaving the labile lignin β-O-4 ether bonds (from 40.9 % to 13.5 %), while leaving the chemically robust C-C linkages and the cellulose backbone largely intact. Consequently, the pretreated fibers exhibited superior mechanical strength (4.13 cN/dtex) compared to traditional alkaline-treated samples (3.56 cN/dtex). This work provides a sustainable, low-severity paradigm for biomass fractionation, offering fundamental insights into the photocatalytic cleavage of lignin inter-unit linkages.
Psychiatric intensive care units have significant implications for patient safety and clinical outcomes. Understanding the demographic and clinical characteristics of restrained patients is essential for developing evidence-based protocols and reducing unnecessary restraint use. The aim of this retrospective descriptive cross-sectional study was to determine the clinical and demographic characteristics of patients subjected to physical restraint in a psychiatric intensive care unit. This descriptive cross-sectional study analyzed 138 patients subjected to physical restraint in a psychiatric intensive care unit between January 2023 and December 2023. Data were collected through systematic chart review using a standardized physical restraint monitoring form from the Hospital Quality and Standards System, designed specifically for type 2 (behavioral safety) restraint documentation. Variables included demographic characteristics, primary diagnoses, restraint indications, and clinical outcomes. Statistical analysis was performed using SPSS, version 28.0. The study followed STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Statistical analysis was performed using descriptive statistics. Out of 138 patients, 95 (68.8%) were male with a mean age of 51.48 Å} 15.02 years. Primary restraint indications included noncompliance with medical treatment (39 patients, 28.3%), severe agitation (37 patients, 26.8%), orientation disturbances (32 patients, 23.2%), and self-harm behaviors (30 patients, 21.7%). The most common primary diagnoses were nonorganic psychosis (55 patients, 39.9%), bipolar disorder (30 patients, 21.7%), and delirium tremens (20 patients, 14.5%). Mean intensive care unit length of stay was 11.87 Å} 14.04 days. This study provides essential baseline data on physical restraint use in psychiatric intensive care, demonstrating male predominance and identifying key clinical indicators. These findings support the development of targeted interventions and evidence-based restraint protocols to optimize patient care while minimizing restrictive practices. Cite this article as: Cengisiz C, Nehir S. Clinical and demographic characteristics of patients subjected to physical restraint in a psychiatric intensive care unit: A retrospective descriptive cross-sectional study. Eurasian J Med. 2026, 58(3), 0961, doi: 10.5152/ eurasianjmed.2026.25961.
The incidence of upper tract urothelial carcinoma is increasing with population aging, yet evidence regarding radical nephroureterectomy (RNU) in very elderly patients is limited. This study evaluated perioperative outcomes, complications, and oncological results of RNU in patients aged ≥85 years compared with younger counterparts. A total of 305 patients who underwent RNU between April 2003 and December 2024 at a tertiary institution were retrospectively reviewed. After excluding those with incomplete data (n = 4), non-urothelial histology (n = 8), or undeterminable pathology (n = 9), 284 patients were eligible. Group A included 24 patients aged ≥85 years, range 85-94 years, and group B included 260 patients <85 years, range 46-84 years. Clinicopathological features, operative outcomes, complications, and survival were compared. Temporal trends and restricted mean survival time (RMST) analyses were also performed. Baseline characteristics were similar (all P > .05). Median laparoscopic operative time was shorter in group A (206 vs. 235 minutes, P = .029). Estimated blood loss, transfusion, and complication rates (10.6% overall; major 2.2%) did not differ (all P > .05). Pathological outcomes were comparable (all P > .05). Adjuvant therapy was less frequent in group A (0% vs. 21.2%, P = .006). Follow-up was 16.3 vs. 35.2, with no differences in survival (all P > .05). The RMST showed shorter survival in group A. The RNU appears feasible in carefully selected patients aged ≥85 years, with perioperative and oncological outcomes broadly comparable to those of younger patients. Chronological age alone should not contraindicate surgery. Restricted mean survival time offers complementary insights into survival estimation in this high-risk population. Cite this article as: Gozu S, Yajima S, Okumura G, et al. Radical nephroureterectomy in the very elderly: A single-center experience of patients aged ≥85 years. Urol Res Pract. 2026, 52, 0125, doi: 10.5152/tud.2026.25125.
Infection is a major complication after trauma and is associated with worse clinical outcomes. Although red blood cell (RBC) transfusion is an essential component of resuscitation in trauma patients, its relationship with infection risk remains controversial. Furthermore, the dose-response relationship has not been fully elucidated. We conducted a retrospective observational study using a nationwide trauma registry in Japan. Trauma patients registered between 2019 and 2021 were included. Patients were categorized into four groups according to RBC transfusion volume within the first 24 h after admission: None (0 units), Low (1-4 units), Moderate (5-9 units), and High (≥ 10 units). The primary outcome was in-hospital infection. Multivariable modified Poisson regression analyses were performed to estimate adjusted risk ratios (RRs) with 95% confidence intervals (CIs). Furthermore, we performed multivariable-adjusted restricted cubic spline analyses with four knots to assess the adjusted dose-response relationship between RBC transfusion volume and the risk of in-hospital infection. A total of 55,807 patients were analyzed. The incidence of in-hospital infection increased across transfusion categories: 4,399/48,308 (9.1%) in the None group, 618/3,724 (16.6%) in the Low group, 396/1,733 (22.8%) in the Moderate group, and 548/2,042 (26.8%) in the High group. In multivariable analysis, compared with the None group, Low (adjusted RR 1.85, 95% CI 1.62-2.10), Moderate (adjusted RR 1.95, 95% CI 1.69-2.26) and High (adjusted RR 2.07, 95% CI 1.76-2.43) transfusion volumes were associated with significantly increased risks of infection, respectively. Restricted cubic spline analyses showed an increase in infection risk at lower transfusion volumes, followed by a plateau at higher transfusion volumes. RBC transfusion volume within the first 24 h after trauma was associated with in-hospital infection risk. The association was generally linear at lower transfusion volumes, whereas a plateau was observed at higher transfusion volumes. Given the observational nature of this study, these findings should be interpreted cautiously.
Pancreatic ductal adenocarcinoma (PDAC) remains a highly aggressive malignancy driven by rapid metastasis and a profoundly immunosuppressive microenvironment. While the surface glycoprotein CD52 is a known immunoregulator, its precise role in solid tumors remains controversial, partly due to its broad expression across diverse cell populations and its compartment-specific functions within the tumor microenvironment. In this study, we utilized integrated single-cell RNA sequencing (scRNA-seq), functional assays, and compartment-specific clinical validation to elucidate the tumor-intrinsic functions of CD52 in PDAC. We identified a highly plastic, restricted subpopulation of CD52-high malignant epithelial cells that actively drives metastasis initiation by enhancing cellular invasive capacity. Concurrently, we demonstrated that tumor-derived CD52 orchestrated a multi-layered immunosuppressive network that attenuates CD8 + T cell cytotoxicity, facilitating early immune evasion. Furthermore, by systematically separating expression sources, our clinical validation established that tumor-derived CD52 is a prognostic indicator of poor patient survival. These findings characterize CD52 as a critical, tumor-intrinsic driver of PDAC progression, highlighting its value as a prognostic biomarker and a therapy target in combination with immune checkpoint blockade to overcome innate therapeutic resistance in PDAC.
Cutaneous leishmaniasis (CL) is an emerging infection in Kerala state. Recent reports showed that Leishmania donovani is causing the dual manifestations, CL and visceral leishmaniasis (VL). In addition, the influx of migrants and returnees from other countries has introduced CL caused by non-endemic variants of Leishmania. A 46-year-old migrant worker from Nepal presented with a single erythematous nodule with crusting and erosions. It was diagnosed as CL through molecular diagnosis, and L. donovani was proven as the parasite by ITS-1 RFLP and sequencing. Additionally, the strain was identified as zymodeme MON-37 by sequence analysis of the 6-PGDH gene. Simultaneously, the phylogenetic analysis revealed the genetic relatedness of the current L. donovani isolate to those previously reported from Nepal. In contrast to the indigenous cases recorded in Kerala, this patient's serum samples showed an unusual rK-39 positivity, and Leishmania DNA was detected in circulation. The patient was successfully treated with intravenous amphotericin B. In the context of the nation attaining VL elimination, the differential tropism of Leishmania species, increasing migrations, and the detection and proper treatment of suspected cases are of high public health significance, as unnoticed cases can create new transmission pockets compromising the elimination efforts. This study signifies the importance of monitoring skin lesions among migrants and returnees from other countries to enhance the National Leishmaniasis Elimination strategies.
The marine fish genera Acanthistius and Trachypoma are restricted to temperate and subtropical rocky reefs of the Southern Hemisphere, with the former comprising 11 species distributed circumglobally and the latter represented by a single species confined to the South Pacific. Both genera have been the subject of more than a century of taxonomic debate, having historically been placed in the families Anthiadidae, Epinephelidae, and Serranidae sensu stricto. Recent molecular studies have placed Acanthistius outside the aforementioned families. However, these studies relied on limited taxon sampling, leaving relationships within Acanthistius and its familial placement unresolved. Similarly, recent morphological evidence has challenged the familial placement of Trachypoma. Here, we present the most comprehensive phylogenetic analysis of Acanthistius and Trachypoma to date (eight of 11 nominal species of Acanthistius), using a combination of mitochondrial genomes and nuclear markers. Our time-calibrated phylogeny supports a monophyletic Acanthistius, with an origin in the mid Eocene to early Miocene and subsequent diversification driven by trans-oceanic dispersal. Our results agree with previous studies in placing both Acanthistius and Trachypoma outside of the Anthiadidae, Epinephelidae, and Serranidae sensu stricto. By integrating our phylogenetic results with morphological and osteological data, we formally recognise the subfamily group name Acanthistiinae and elevate it to family rank as Acanthistiidae. We also erect a new family, Trachypomatidae fam. nov., to accommodate Trachypoma.
Analysis of left-truncated and interval-censored survival data is challenging, particularly when the failure time and observation process are dependent. Existing methods, including Sun et al. (2023), model dependency via copulas, which may be restrictive in the presence of complex interval-censoring mechanisms. To address this gap, we propose the first shared frailty model specifically designed for left-truncated, interval-censored data, capturing heterogeneity and dependency between the failure time and observation processes. A sieve maximum likelihood approach is developed, using I-splines and M-splines to approximate the unknown baseline hazard and examination intensity functions. The asymptotic properties of the estimators are established, and an extensive simulation study demonstrates that the method provides consistent, efficient, and robust parameter estimates under a variety of scenarios. The approach is illustrated through a real data application to the AIDS cohort study, highlighting its ability to account for left truncation, interval censoring, and dependent observation process.