Total factor productivity (TFP) serves as a critical indicator for measuring enterprise efficiency and technological progress. However, existing prediction methods often fail to distinguish genuine causal mechanisms from spurious correlations while neglecting inter-enterprise network dependencies. This study proposes a Causal-Temporal Graph Convolutional Network (CT-GCN) that integrates causal inference techniques with temporal graph convolutional networks for dynamic TFP prediction and optimization. The framework employs the Levinsohn-Petrin method for TFP estimation, double machine learning for causal effect identification, and constructs enterprise relationship graphs capturing supply chain linkages, geographic proximity, and technological similarity. Using panel data from 12,847 Chinese manufacturing enterprises spanning 2008-2022, empirical results demonstrate that CT-GCN achieves substantial prediction improvements over baseline models, with RMSE reductions exceeding 19%. The causal analysis identifies R&D investment, digital transformation, and human capital as genuine productivity drivers, with significant treatment effect heterogeneity across industry sectors, firm sizes, and regions. An optimization decision mechanism translates these insights into differentiated strategic recommendations. This research contributes a novel methodology bridging causal reasoning and deep learning for economic forecasting applications.
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Subjective well-being is a central component of physical and mental health and is increasingly recognized as a key indicator of quality of life. Despite the widespread use of the PERMA framework, no validated French version of the PERMA-Profiler is currently available. The aim of this study was to translate and culturally adapt the PERMA-Profiler into French and to examine its psychometric properties in a large sample of adults. A total of 612 French-speaking adults completed the French version of the PERMA-Profiler as well as measures of flourishing, anxiety and depression. The sample was randomly divided into two independent subsamples to conduct exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The EFA suggested a parsimonious three-factor solution, while comparative model tests confirmed the theoretical five-factor structure of the PERMA model. The CFA conducted on an independent subsample strongly confirmed a correlated five-factor model, as well as a second-order hierarchical model reflecting a general well-being factor. The PERMA-Profiler demonstrated good to excellent internal consistency for most dimensions and for the total score, although the "engagement" dimension showed lower reliability, which is consistent with previous validation studies. Test-retest analyses indicated good temporal stability for the total score and most subscales. Convergent validity was confirmed by strong positive associations with flourishing and perceived happiness. Discriminant validity was evidenced by weaker associations with anxiety, depression, loneliness and negative emotions than with flourishing, although some correlations with HADS anxiety and depression scores reached moderate to strong magnitude. Overall, the French version of the PERMA-Profiler has robust psychometric properties and supports the multidimensional structure of psychological well-being proposed by the PERMA framework. This instrument is a reliable and theoretically grounded tool for assessing the well-being of French-speaking adult population, while highlighting the distinct psychometric behavior of the Engagement dimension.
Sweet orange (Citrus sinensis L.) is a major fruit crop globally, but fungal pathogens have severely impacted its yield. Bilo Nopha, known for high-quality sweet oranges, has recently faced significant preharvest spoilage. This study aimed to isolate fungal pathogens associated with preharvest spoilage of sweet orange (Citrus sinensis L.) fruit in Bilo Nopha, southwestern Ethiopia. In the present study, a total of 240 symptomatic orange fruit samples were collected from six orchards of study area and fungi pathogens were isolated and characterized to genus level following standard microbiological techniques. A total of 430 fungal isolates were recovered. Pseudocercospora spp. were most prevalent (45.0%), followed by Colletotrichum spp. (42.1%). Alternaria spp. showed moderate prevalence (30.4%) with significant site variation (15.0-37.5%, P < 0.05). Rhizopus spp. were consistent across sites (20-30%, total 27.1%), while Fusarium and Phytophthora spp. had the lowest rates (17.5% each). Pseudocercospora spp., Colletotrichum spp., and Phytophthora spp. were identified as the primary fungal pathogens, whereas Alternaria spp., Rhizopus spp., and Fusarium spp. were involved as secondary or opportunistic pathogens. Species-level identification and targeted management are recommended to reduce losses and sustain production.
Given concerns that screen time may impact dietary habits, this study investigated the association between screen time and dietary intake among adolescents in the United States. We analyzed a prospective cohort (N = 6485, 47.3% female, age: 12 ± 0.7 years) from the Adolescent Brain Cognitive Development (ABCD) Study, using data from Year 2 (2018-2020) and Year 3 (2019-2021). Multinomial logistic regression models estimated the associations between participant-reported screen time (watching television shows and videos, playing video games, socializing, browsing the internet, and total screen time (hours/day)) and parent/participant-reported intake of various food/nutrient categories 1 year later (Year 3). We adjusted for age, sex, race and ethnicity, household income, parent education, average daily kilocalorie intake, respective food or nutrient, and study site (Year 2). Each additional hour of most screen time modalities was prospectively associated with higher odds of consuming fewer fruits, vegetables, whole grains, legumes, fiber, and dairy, and higher glycemic index, and higher odds of consuming more added sugars and a higher polyunsaturated fats ratio 1 year later. These findings highlight the need for parental guidance and clinical interventions to support screen time habits and promote healthy dietary choices among adolescents. This study examines the association between contemporary screen time modalities and dietary intake 1 year later in a demographically diverse U.S. sample of early adolescents. Most screen time modalities, such as total screen time and watching television shows and videos, were prospectively associated with higher odds of consuming fewer fruits, vegetables, whole grains, legumes, and fiber 1 year later. Greater total screen time and time spent socializing were prospectively associated with higher odds of a higher polyunsaturated fats ratio 1 year later.
Epirubicin (EPI) can cause metabolic side effects, including chemotherapy-related diabetes, partly through oxidative stress that disrupts zinc (Zn) homeostasis and impairs autophagy. This study investigated the effects of EPI on Zn regulation and autophagy in the pancreas, as well as the modulatory role of N-acetylcysteine (NAC). Rats received EPI (9.6 mg/kg) by intraperitoneal injection (i.p.) followed 1 h later by NAC (50 or 300 mg/kg, i.p.). Glucose homeostasis was assessed using the Homeostatic Model Assessment (HOMA-IR), and β-cell function was assessed using HOMA-β levels. Plasma insulin levels, as well as insulin, proinsulin, beclin, autophagy-related proteins (ATG5), Microtubule-Associated Protein 1 Light Chain 3 (LC3), phosphorylated Akt (p-Akt), mechanistic target of rapamycin complex 1 (mTOR1), cleaved caspase-3, Zrt/Irt-like Protein 10 (ZIP10), and the proliferation marker Ki-67 in pancreatic tissue, were measured using commercial ELISA kits. Total oxidant status (TOS) and total antioxidant status (TAS) were measured using commercial colorimetric assay kits, and the oxidative stress index (OSI) was calculated. Zn levels in pancreatic tissue and plasma samples were measured using a colorimetric method. Morphological changes in the pancreas were assessed by hematoxylin and eosin staining. As a result, in the EPI group, oxidative stress and ZIP10 levels increased, whereas Zn levels decreased, as well as pancreatic autophagy, proliferation, and insulin synthesis increased. Oxidative stress decreased in both the EN-50 and EN-300 groups, with a more pronounced decrease in the EN-300 group. Furthermore, in the EN-300 group, pancreatic Zn, ZIP10, autophagy, and proliferation levels decreased, whereas mTOR1 levels increased. The pancreatic insulin synthesis observed in the EN-50 group was not observed in the EN-300 group. In conclusion, the increased autophagy observed in the Epi group may reflect an adaptive response to oxidative stress. The effects of NAC on oxidative stress may be dose-dependent, and high-dose NAC administration may suppress EPI-induced autophagy via mTOR1-mediated signaling. Furthermore, the relationship among Zn levels, autophagy, and insulin synthesis observed in the experimental groups may contribute to a better understanding of EPI-associated diabetogenic alterations.
To translate, culturally adapt, and evaluate the reliability and construct validity of the Korean version of the Haemophilia Activities List (HAL) in adult patients with hemophilia. This cross-sectional validation study included adult patients with hemophilia A and B. The HAL was translated into Korean using a standardized forward-backward translation process according to international guidelines. The participants completed the Korean HAL, the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L), and the Routine Assessment of Patient Index Data 3 (RAPID3) questionnaire. Internal consistency was assessed using Cronbach's alpha, test-retest reliability was assessed using intraclass correlation coefficients (ICCs), and construct validity was assessed using Spearman's correlation analysis. A total of 87 adult patients completed the questionnaire. The mean age was 37 years (range, 18-62 years), and most participants had severe hemophilia. The Korean HAL demonstrated high internal consistency, with a Cronbach's alpha coefficient of 0.97 for the total score and domain-specific values ranging from 0.78 to 0.95. The test-retest reliability was excellent, with an overall ICC of 0.95. Construct validity was supported by strong correlations between the HAL and EQ-5D-5L overall scores (r = 0.78, p < 0.01) and strong correlations with RAPID3 physical function scores (r = -0.82, p < 0.01). The Korean version of the HAL demonstrated excellent reliability and good construct validity in adult patients with hemophilia. These findings support the use of the Korean HAL as a reliable and culturally appropriate patient-reported outcome measure to assess functional limitations in clinical practice and research.
The present study investigated the individual and combined effects of lactic acid and rosemary meal on growth performance, biochemical parameters, immune responses, the expression of growth and antioxidant-related genes, intestinal morphology, and oxidative status in Nile tilapia (Oreochromis niloticus). A total of 120 apparently healthy fish, with an average weight of 3.03 ± 0.02 g, were randomly assigned to four equal groups, each consisting of three replicates. Four experimental diets were formulated: a basal control diet (CON), a basal diet supplemented with 1 g of lactic acid per kg of diet (LA), a basal diet containing 10 g of rosemary per kilogram of diet (RM), and a basal diet that included both supplements (LA + RM). Fish were fed these diets for a duration of 60 days. The results indicated that either lactic acid or rosemary alone or in combination had a greater growth-stimulating impact than the CON group (P ≤ 0.05) with superiority to the combination group (LA + RM group). Activities of aspartate aminotransferase and alanine aminotransferase, along with creatinine and urea levels, were significantly reduced (P ≤ 0.05) in the groups of lactic acid and rosemary alone or in combination relative to the CON group. Total protein and albumin concentrations were elevated in the LA + RM group (P ≤ 0.05). Intestinal histology revealed normal morphology across groups, with increased villus height, intestinal villi spacing, and goblet cell density in LA + RM (P ≤ 0.05) without pathological lesions in the liver and spleen. Antioxidant, immune, and growth-related gene expressions were upregulated in RM and LA + RM groups. In conclusion, rosemary supplementation, alone or combined with lactic acid, enhanced fish health status and upregulated target genes without pathological lesions with superiority to the combination treatment.
Patients undergoing temporomandibular joint (TMJ) surgery can develop chronic postsurgical pain (CPSP). This study identifies patient factors and CPSP characteristics after TMJ surgery. Survey-based study of patients who underwent TMJ surgery at Massachusetts General Hospital between 08/1987-06/2024. Survey evaluates CPSP, comorbidities, and risk factors 6+ months postoperatively. Total of 104 patients responded. Male:female ratio 1:12; median follow-up 2.2 years. Total of 74.0% patients report ongoing TMJ pain since last surgery. CPSP noted in 77.3% patients who underwent minimally invasive TMJ surgery and 68.0% patients who underwent open surgery. CPSP is more prevalent in patients with bilateral TMJ surgery as opposed to unilateral surgery (P = .03). No significant difference noted in the mean preoperative pain score among patients with/without CPSP. Pain intensity is mild-moderate and common descriptors are aching, throbbing, and tender. Overall, 13% (n = 10/77) of patients with CPSP had a likely neuropathic component of the pain. Rates of pain interference (P < .001) and pain catastrophizing (P < .001) are higher in patients with CPSP. There is a high prevalence of CPSP after TMJ surgery; symptoms resemble myofascial pain, although neuropathic qualities may be present. Patients with CPSP are more likely to have undergone bilateral surgery and experience increased catastrophizing, pain interference, and disability.
The present study evaluated the influence of olive paste pH adjustment during malaxation on oil yield and quality parameters of virgin olive oil obtained from Olea europaea L. cv. Gemlik. The pH of olive paste was systematically adjusted to 2.7-6.7 using citric acid and NaOH solutions during malaxation. Oil yield, free fatty acidity (FFA), peroxide value (PV), total and individual phenolic compounds, DPPH radical scavenging activity, and color attributes (L*, a*, b*) were determined. Oil yield ranged from 28.67 to 45.11%, with the highest yield observed at pH 6.7. Total phenolic content(TPC)showed a clear pH-dependent pattern, reaching 678 mg GAE kg⁻¹ at pH 2.7 and decreasing to 281 mg GAE kg⁻¹ at pH 6.7. Moderately acidic conditions (pH 4.7) promoted elevated concentrations of secoiridoid derivatives, with oleacein (257 mg kg⁻¹) and oleocanthal (159.7 mg kg⁻¹) attaining their highest levels. Phenolic alcohols exhibited compound-specific pH responses, with tyrosol and hydroxytyrosol acetate reaching maximum levels at pH 4.7, while hydroxytyrosol peaked at pH 3.7 and declined thereafter. Flavonoids, such as apigenin, reached maximum concentrations (16.5 mg kg-¹) under mildly acidic conditions (pH 3.7). 3,4-DHPEA-EA decreased progressively with increasing pH, from 226 to 103 mg kg-¹, indicating that pH influences its stability and transformation pathways during malaxation. PV values were highest at pH 3.7 (8.4 meqO2kg⁻¹ oil) and 4.7 (7.2 meqO2kg⁻¹ oil). DPPH radical scavenging activity paralleled the phenolic profile, with oils obtained at lower pH exhibiting approximately twofold greater activity than those obtained at pH 5.7 and 6.7. Several quality parameters exhibited significant quadratic responses to pH variation. Color attributes were also influenced by pH, with acidic conditions producing brighter oils with reduced yellowness. These findings indicate that controlled pH modulation during malaxation can influence phenolic composition, antioxidant capacity, and visual characteristics of virgin olive oil, providing mechanistic insight into the pH sensitivity of its extraction and compositional changes.
Moyamoya angiopathy (MMA) is a cerebrovascular disease treated by surgical revascularization. This study aimed to present long-term outcomes of European MMA patients after surgical revascularization. MMA patients treated surgically between 1998 to 2023 were included. Follow-up comprised clinical and radiological examinations and electronic questionnaires. Patient data were analyzed retrospectively, and logistic regressions were performed to identify predictors of unfavorable outcomes. A total of 276 patients with 428 surgically treated hemispheres were included. The mean age was 35.0 ± 17.2 years, including 192 women and 84 men, predominantly of Caucasian ethnicity (88.0%). Ischemia (82.2%) and hemorrhage (10.1%) were the most common symptoms at onset. Most adults (80.9%) were treated with combined bypass surgery via mini-craniotomy. Within 30 days, complications occurred in 6.3% of surgeries, and the perioperative stroke risk was 2.6%. A total of 148 patients underwent in-house follow-up. No mRS scores ≥ 5 were observed, with 86.3% of patients achieving a score of 0-2, alongside a bypass patency rate of 95.7% and a stroke risk of 0.3% per patient-year. Preoperative stroke and silent ischemic MRI lesions were identified as predictors of an unfavorable outcome. Additionally, 201 patients were followed up electronically. No mRS scores ≥ 5 were observed, with 87.9% of patients achieving a score of 0-2. Moreover, 90.7% were independent in daily life, but only 50.5% returned to work or school. Combined bypass surgery yielded favorable outcomes with low complication and stroke rates. Patients with preoperative stroke require closer follow-up, and individualized strategies are needed to address persistent functional impairments.
Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by chronic inflammation and progressive joint destruction. Tenosynovitis is one of the early manifestations of RA. This study aims to develop a machine learning (ML)-based model using ultrasound (US) radiomics to objectively diagnosis tenosynovitis in RA patients, thereby facilitating accurate evaluation of RA. This study included a total of 1496 grayscale US images of the wrist extensor tendons, wrist flexor tendons, and finger flexor tendons from 152 patients with RA. Radiomic features were extracted from the US images. The radiomic features and a total of 10 clinically relevant features were selected to train machine learning model. To avoid data leakage, the dataset was partitioned at the patient level with 80% allocated to the training set and 20% to the test set. The model was trained for 100 epochs with an early stopping strategy (halted if no test set performance improvement was observed for 10 consecutive epochs) to prevent overfitting. Comparative experiments were conducted against two conventional ML methods: Support Vector Machine (SVM) and Random Forest (RF). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), F1 score, accuracy, and the area under the receiver operating characteristic curve (AUC) of the model were calculated. Calibration curves and decision curve analysis (DCA) were employed to assess the model's clinical utility, and the average per-case processing time was measured to verify real-time applicability. The dataset comprised 1196 images for training and 300 images for testing. In the training set and the test set, the AUC reached 0.969 and 0.914 respectively. The model demonstrated robust performance on the test set, with a sensitivity of 0.881, specificity of 0.788, PPV of 0.505, NPV of 0.964, F1 score of 0.642 and accuracy of 0.807. The model also outperformed SVM (AUCs: 0.909 and 0.881) and RF (AUCs: 0.955 and 0.880) on the training and test sets, respectively. The average processing time per case was 0.8 s, which meets the real-time operational requirements of clinical settings. Calibration curves indicated excellent agreement between predicted and observed outcomes, while DCA confirmed the model's clinical applicability and predictive accuracy across both training and test datasets. The XGBoost-based machine learning model developed in this study could effectively diagnosed tenosynovitis on US imaging for RA patients, outperforming SVM and RF. Owing to its real-time processing capability, the model has potential to facilitate the accurate evaluation of RA.
Intestinal mucosal healing is a key indicator for evaluating therapeutic efficacy and predicting long-term prognosis in ulcerative colitis (UC). Short-chain fatty acids (SCFAs) play an important role in maintaining intestinal homeostasis and promoting mucosal repair; however, their quantitative association with UC mucosal healing has not been fully elucidated. This study aimed to investigate the association between SCFA levels and endoscopic mucosal healing in UC patients and evaluate their clinical value as predictive biomarkers. This prospective cohort study enrolled 154 UC patients from January 2024 to March 2025, who were divided into a mucosal healing group (n = 68) and a non-healing group (n = 86) according to Mayo endoscopic scores, with an additional 50 healthy controls. Endoscopic evaluations were independently scored by two experienced gastroenterologists with substantial inter-rater reliability (κ = 0.82). Gas chromatography-mass spectrometry was used to detect fecal SCFA concentrations, and real-time quantitative PCR (PCR stands for Polymerase Chain Reaction, a core molecular biology technique that allows for the rapid and specific amplification of specific DNA or RNA fragments in vitro) was employed to detect the expression levels of SCFA transporter protein SLC16A1 and metabolic enzyme genes in mucosal tissues. The association between SCFA levels and mucosal healing indicators was analyzed using multiple logistic regression adjusted for age, gender, disease duration, disease extent, and current medications. The total fecal SCFA concentration in UC patients was significantly lower than that in healthy controls (P < .001). The butyrate concentration in the mucosal healing group was significantly higher than that in the non-healing group ([16.8 ± 7.3] vs [10.2 ± 4.6] mmol/kg, P < .001). The SLC16A1 mRNA expression level in the mucosal healing group was 2.3-fold higher than that in the non-healing group, while ACSM3 and ACADS expression levels were elevated by 1.8-fold and 1.6-fold, respectively (all P < .001). Fecal butyrate concentration showed a significant negative correlation with Mayo endoscopic score (r = -0.647, P < .001). Multiple regression analysis revealed that fecal butyrate concentration was an independent predictor of mucosal healing (OR = 1.18, 95% CI: 1.09-1.28, P < .001). Receiver operating characteristic analysis demonstrated that butyrate had an area under the curve (AUC) of 0.847 for predicting mucosal healing, with a sensitivity of 76.5% and specificity of 81.4%. A combined model incorporating butyrate, C-reactive protein, and corticosteroid use achieved superior diagnostic performance (AUC = 0.896). The associations remained consistent across different disease extents and medication subgroups. Fecal SCFA levels in UC patients, particularly butyrate concentration, are closely associated with the degree of intestinal mucosal healing. Fecal butyrate concentration can serve as a non-invasive biomarker for assessing mucosal healing status in UC patients, providing objective evidence for individualized therapeutic strategy development. This prospective cohort study included 154 UC patients and 50 healthy controls to explore short-chain fatty acid (SCFAs) association with intestinal mucosal healing. UC patients had lower fecal SCFAs; the mucosal healing group showed higher butyrate and elevated butyrate metabolism-related gene (SLC16A1, ACSM3, ACADS) expression. Fecal butyrate independently predicted mucosal healing (area under the curve [AUC] = 0.847), with a combined model (butyrate + C-reactive protein + corticosteroid use) showing better performance (AUC = 0.896). Conclusion: Fecal butyrate is a non-invasive biomarker for the UC mucosal healing, aiding personalized treatment and reducing endoscopy reliance.
The triglyceride-glucose (TyG) index and atherogenic cholesterol markers, including non-HDL cholesterol and remnant cholesterol, are significant predictors of atherosclerotic cardiovascular disease (ASCVD). However, the joint effects and predictive value of TyG and atherogenic cholesterol markers for incident stroke remain insufficiently understood. We included participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled at baseline in 2011 and followed them through 2020. Participants were categorized into four groups according to the median values of the TyG index and each cholesterol marker, with those having both values below the median serving as the reference group. Cox proportional hazards models were used to evaluate the independent and joint associations of TyG and atherogenic cholesterol markers with incident stroke. Restricted cubic spline models were applied to assess dose-response relationships, and receiver operating characteristic (ROC) curve analyses were used to examine predictive performance. A total of 8,544 participants were included (mean [SD] age 59.0 [9.5] years; 52.1% female). 522 incident stroke events occurred during a maximum follow-up of 9.0 years. TyG, non-HDL cholesterol and remnant cholesterol were all independently associated with stroke risk. Compared with participants with both TyG and cholesterol markers below median, those with both markers above median had the greatest stroke risk in fully adjusted models (HR for high TyG and high non-HDL cholesterol: 1.76 [95% CI 1.41-2.20]; HR for high TyG and high remnant cholesterol: 1.45 [95% CI 1.18-1.77]). Adding TyG and each cholesterol marker to traditional risk factors modestly improved risk discrimination, with the model combining TyG and non-HDL cholesterol yielding the highest AUC. The TyG index and atherogenic cholesterol markers were independently and jointly associated with increased stroke risk among middle-aged and older adults. Adding these routinely available metabolic and lipid markers modestly improved discrimination for incident stroke.
Neuroimmune communication is essential for regulating inflammation and maintaining cardiovascular homeostasis, but the role of sensory pathways in this process is poorly understood. Arterial baroreceptors are typically defined as mechanoreceptors essential for arterial pressure homeostasis and have been associated with modulation of the immune response. However, their role in sensing systemic inflammation remains unknown. Here, we establish the molecular profile of the rat aortic depressor nerve (ADN) as an immune-competent tissue and investigate its response to lipopolysaccharide (LPS)-induced endotoxemia. Using analysis of gene expression, total protein quantification, and immunofluorescence assay, we demonstrate that the ADN, from male Sprague-Dawley rats (7-8 weeks old), constitutively expresses key components for innate immune signalling, including Toll-like receptor 4 (TLR4), MyD88, and phosphorylated NF-κB, indicating a state of constant immunological vigilance. LPS administration induced an inflammatory response within the ADN, upregulating gene expression of NF-κB, interleukin-6, and type I interleukin 1 receptor, and it also increased the ADN electrical activity. Notably, the increase in nerve firing occurred while the animals were experiencing systemic hypotension and also during the diastolic phase, indicating that this response is not from the mechanosensory reflex. Furthermore, we characterized the progression of this immune response in the nodose ganglion and aortic arch, identifying a coordinated neuroimmune sensory axis. These findings reposition arterial baroreceptors from purely mechanoreceptors to integrative immunosensors that actively detect and respond to systemic inflammation. This novel neuroimmune circuit represents a critical link between inflammation and cardiovascular system, offering a novel therapeutic target for treating cardiovascular and inflammatory conditions.
Enteral nutrition feeding intolerance (ENFI) is a common complication in patients with sepsis and may compromise nutritional support and clinical recovery. This study aimed to develop and validate a risk stratification model incorporating serum lactate (LAC) and albumin (ALB) for predicting ENFI in patients with sepsis. A total of 258 patients were screened for eligibility according to predefined inclusion and exclusion criteria. The final complete-case cohort comprised 230 patients with sepsis who received enteral nutrition between December 2021 and June 2025, including 88 patients in the ENFI group and 142 in the non-ENFI group. Clinical variables and laboratory indicators obtained within 24 hours before enteral nutrition initiation were analyzed. Predictors were screened using least absolute shrinkage and selection operator regression and entered into multivariable logistic regression for model construction. Model performance was evaluated by receiver operating characteristic analysis, calibration analysis, bootstrap internal validation, and decision curve analysis. Lactate levels were significantly higher in the ENFI group than in the non-ENFI group (median [interquartile range], 2.70 [2.00-3.86] vs 1.82 [1.19-2.48] mmol/L; P < 0.001), whereas ALB levels were significantly lower (27.83 ± 5.02 vs 32.82 ± 4.33 g/L; P < 0.001). Least absolute shrinkage and selection operator regression identified 4 predictors: ALB, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, LAC, and mechanical ventilation. Multivariable analysis showed that decreased ALB (odds ratio [OR] = 0.80; 95% CI, 0.74-0.86), increased APACHE II score (OR = 1.09; 95% CI, 1.01-1.17), increased LAC (OR = 2.03; 95% CI, 1.50-2.85), and mechanical ventilation (OR = 2.52; 95% CI, 1.28-5.10) were independent predictors of ENFI (all P < 0.05). The 4-variable model achieved an area under the curve of 0.854 (95% CI, 0.803-0.905), outperforming single indicators. Bootstrap internal validation yielded a corrected area under the curve of 0.845, and the Hosmer-Lemeshow test indicated good fit (P = 0.299). Decision curve analysis reported a positive net clinical benefit across a threshold probability range of 10% to 70%. A 4-variable prediction model anchored by LAC and ALB and further incorporating APACHE II score and mechanical ventilation showed good discrimination for predicting ENFI in patients with sepsis. This model may provide a practical tool for early risk stratification and may help support individualized enteral nutrition monitoring in clinical practice.
Tertiary Trauma Surveys (TTS) are designed to identify injuries which are not recognised during the primary and secondary surveys. These injuries occur in up to 40% of patients and are commonly referred to in the literature as "missed", we prefer the term "unrecognised" as this term does not infer the failure of primary and secondary survey, rapid assessments designed to identify life and limb threatening injuries. The incidence and definition of unrecognised injuries varies across studies, and several risk factors have been identified internationally. The aim of our study was to investigate the sensitivity and specificity of TTS and the incidence and risk factors for unrecognised injuries in a large UK Major Trauma Centre (MTC). Data was prospectively collected for all major trauma patients admitted to our MTC over six months. All patients over 16 years with an ISS≥ 9 were included. Patients with a length of stay of less than 24 h or palliated were excluded. All patients were examined using a specific TTS protocol. Patient records were reviewed one year post admission to identify any injuries diagnosed after discharge. A total of 293 patients were included. Unrecognised injuries were identified at TTS in 18.8% (55/293) patients, most commonly affecting the face or head and eyes. Patients with unrecognised injuries had a higher admission ISS (p = 0.020) and were more likely to present out of hours (40/179 vs 15/104; adjusted OR 2.23 [95% CI 1.12-4.28], p = 0.030). In patients with ISS 9-15, unrecognised injuries occurred in 27/170 (15.9%). Injuries identified after discharge occurred in 1/263 (0.38%). The sensitivity and specificity of the TTS were 53/55 (96.3%) and 238/238 (100%), respectively. Injuries identified at TTS remain common in major trauma patients including those with ISS between 9-15. TTS is an essential component of major trauma patient assessment and can be highly sensitive and specific. It should include examination of the head and eyes.
To describe the effectiveness and safety of pembrolizumab in routine clinical practice as first-line treatment for advanced/metastatic non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50% and without EGFR or ALK alterations. Retrospective, multicenter observational study including patients diagnosed with advanced/metastatic NSCLC treated with pembrolizumab monotherapy as first-line therapy between January 2016 and July 2020. Clinical, treatment-related, and safety variables were collected. The primary effectiveness endpoints were overall survival (OS) and progression-free survival (PFS), estimated using the Kaplan-Meier method. A total of 1005 patients from 42 Spanish hospitals were included, with a median age of 67 years (interquartile range [IQR]: 14); 256 were women. The predominant histology was non-squamous (725 patients). Median follow-up was 17.9 months (IQR: 24.1), and the median number of treatment cycles received was 8 (IQR: 21). Median PFS and OS were 8.7 months (95% confidence interval [CI]: 7.2-10.1) and 18.0 months (95% CI: 16.2-21.3), respectively. In the bivariate analysis, factors significantly associated with shorter OS included: age ≥ 75 years, body mass index (BMI) <25 kg/m2, never smoking, performance status (PS-ECOG) ≥2, squamous histology, baseline liver or brain metastases, ≥2 metastatic sites at diagnosis, Lung Immune Prognostic Index (LIPI) 1-2, and prior exposure to proton pump inhibitors (PPIs), corticosteroids, and antibiotics (within the previous 10 days). Overall, 61.7% of patients experienced some degree of toxicity (G1-5), and 15.3% had G ≥ 3 toxicities. Treatment discontinuation due to toxicity occurred in 115 patients (12.7%). Patients who developed toxicity had a median OS of 28.3 months (95% CI: 23.9-34.5), compared to 6.5 months (95% CI: 5.1-9.2) in those without toxicity (p < 0.0001). In advanced/metastatic NSCLC with PD-L1 ≥ 50% and no EGFR/ALK alterations, first-line pembrolizumab demonstrates outcomes consistent with the pivotal trial and with published real-world evidence. The findings confirm that PS-ECOG ≥2 and prior PPI exposure are predictors of shorter OS, and that the development of toxicity during treatment is significantly associated with longer survival.
Periodontitis has been recognized as a contributing factor in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the precise mechanisms through which periodontitis influences the pathogenesis of MASLD remain unclear. This study aimed to investigate the association between experimental periodontitis and MASLD severity and to explore the potential underlying mechanisms using a ligature-induced periodontitis model under low-fat diet (LFD) and high-fat diet (HFD) conditions. A total of 40 mice were divided into four groups: low-fat diet control group (LFD-Ctrl), low-fat diet with periodontitis group (LFD-Perio), high-fat diet control group (HFD-Ctrl), and high-fat diet with periodontitis group (HFD-Perio), with 10 mice initially assigned to each group. Mice were fed an HFD for 12 weeks to establish the MASLD model, followed by ligature-induced periodontitis for 4 weeks. Periodontal inflammation and alveolar bone loss were assessed using micro-computed tomography (Micro-CT), hematoxylin and eosin (H&E) staining, and tartrate-resistant acid phosphatase (TRAP) staining, while MASLD severity was evaluated via hepatic H&E staining, Oil Red O staining, periodic acid-Schiff (PAS) staining, Masson's Trichrome staining, nonalcoholic fatty liver disease activity score (NAS), alpha-smooth muscle actin (α-SMA) expression, pericellular fibrosis, and serum lipid and liver enzyme measurements. Compared with HFD-Ctrl mice, HFD-Perio mice exhibited aggravated MASLD-related phenotypes, including elevated fasting blood glucose, significantly increased homeostatic model assessment for insulin resistance (HOMA-IR) (2.89 ± 0.67 vs. 1.93 ± 0.26, P < 0.0001), higher nonalcoholic fatty liver disease activity score (NAS) (4.57 ± 0.71 vs. 2.30 ± 0.33, P < 0.01), and more pronounced pericellular fibrosis. Gut microbiota analysis showed that the Firmicutes/Bacteroidota ratio was further increased in HFD-Perio mice compared with HFD-Ctrl mice (9.39 ± 2.82 vs. 5.48 ± 1.98, P < 0.05), accompanied by enrichment of the genus Helicobacter. These findings indicate that experimental periodontitis aggravates HFD-induced MASLD phenotypes, potentially via metabolic dysregulation, liver inflammation and fibrosis, and gut microbiota dysbiosis, highlighting the need for further studies to clarify whether periodontal health influences MASLD progression.
This multicenter, retrospective real-world study evaluated the efficacy and safety of aflibercept 2 mg biosimilar SB15 (Afilivu®) across multiple retinal diseases. A total of 1083 eyes from 984 patients received 2762 injections between March 2023 and February 2025 at three South Korean tertiary centers, comprising 188 treatment-naïve (17.4%) and 895 switching eyes (82.6%). Diagnoses included neovascular age-related macular degeneration (nAMD, n = 611), retinal vein occlusion (RVO, n = 182), diabetic macular edema (DME, n = 173), and other conditions (n = 117). Over a mean follow-up of 5.17 ± 2.76 months with 2.55 ± 1.09 injections, central foveal thickness decreased significantly by - 47.5 µm (95% CI - 55.2 to - 39.8; P < 0.001), while best-corrected visual acuity remained stable (mean change - 0.003 LogMAR; P = 0.572). Treatment-naïve eyes demonstrated greater anatomical improvement than switching eyes (- 93.9 vs. - 37.9 µm; P < 0.001). Retinal fluid resolved significantly across diagnostic groups: in nAMD, subretinal fluid decreased from 51.2 to 29.6% (P < 0.001); in RVO, intraretinal fluid reduced from 92.9 to 76.4% (P < 0.001); and in DME, intraretinal fluid decreased from 90.8 to 84.4% (P = 0.002). One case (0.09%) of rhegmatogenous retinal detachment occurred; no intraocular inflammation or other serious adverse events were observed. These findings support the real-world effectiveness and safety of SB15 (Afilivu®) in both treatment-naïve and switching populations across diverse retinal diseases.