Eosinophilic Esophagitis (EoE) is a chronic inflammatory disorder with variable macroscopic and microscopic findings and clinical presentations, complicating management. This study examines esophageal sampling practices, segmental disease patterns, and longitudinal treatment trends and outcomes in pediatric EoE. We retrospectively reviewed charts of 138 pediatric EoE patients diagnosed between 2009 and 2023. EoE was defined as compatible symptoms and ≥ 15 eosinophils per high-power-field without alternative explanation. Diagnostic endoscopy was defined as the first endoscopy performed for evaluation of symptoms showing ≥ 15 eosinophils. Data included demographics, symptoms, macroscopic/microscopic findings, sampling methods, and treatments. Mean age at diagnosis was 8.33 ± 5.37 years, 75% male. Most common presenting symptoms were vomiting (39.28%), dysphagia (32.14%) and food impaction (28.57%). Among 112 diagnostic endoscopies, macroscopic abnormalities were most frequent in the lower esophagus (85.71%), with furrows (69.64%) and exudates (55.36%) predominating. Multi-level sampling in patients with ≥ 15 eosinophils in one field, revealed < 15 eosinophils in 21.11% of upper, 7.14% of middle, and 14.14% of lower esophageal samples. Microscopic findings despite normal endoscopic appearance were most common in the upper (26.4%, p < 0.001), and less frequently in the lower (9.8% p = 0.002) esophagus. Remission following first-line therapy was achieved in 44 patients (48.35%). Biologic therapy was initiated after multiple prior treatment failures and resulted in histologic remission in all treated patients (n = 9).  Findings indicate greater disease severity distally and underscore the need for multi-regional sampling, even in normal-appearing areas. Therapeutic responses are heterogenous and limited, and biologic therapies show promise but require validation in larger studies. • Pediatric eosinophilic esophagitis (EoE) is a chronic immune-mediated disease with variable endoscopic findings, requiring both compatible clinical features and histologic evidence of ≥15 eosinophils per high-power field. • Empiric elimination diets and proton pump inhibitors are considered first-line treatments, with variable remission rates. • Pan-esophageal multi-level biopsies, including from normal-appearing mucosa, improve diagnostic accuracy. • While first-line therapies show mild success rates, real-world data demonstrate complete histologic remission with biologic therapy, supporting its promise for pediatric EoE.
Cardiac rhabdomyoma is the most common primary cardiac tumor in infancy and is frequently associated with tuberous sclerosis complex (TSC). A 5-month-old asymptomatic infant presented with electrocardiography (ECG) showing marked ST-segment elevation in the anterolateral and inferior leads. Echocardiogram showed a cardiac rhabdomyoma in the left ventricle with preserved ventricular function and no evidence of hemodynamic compromise. Cardiac biomarkers were negative. There was no other evidence, clinically or radiologically, for TSC. Genetic testing for TSC was also negative. The infant remained clinically well with persistent but stable ECG changes at 10-month follow-up. This case highlights a rare but striking ECG presentation of a benign cardiac tumor, emphasizing the importance of clinical context when interpreting ischemic-appearing ECG changes in infants. Cardiac rhabdomyomas may present with marked ST-segment elevation on ECG, even in the absence of symptoms or myocardial injury. Ischemic-appearing ECG changes in infants with cardiac tumors may follow a benign clinical course and warrant careful longitudinal assessment rather than immediate intervention.
In the search for more efficient chemical processes to valorize renewable feedstocks, oleate hydratases (Ohys) represent promising biocatalysts. These enzymes can convert cis-Δ9 fatty acids like oleic acid into their hydroxy fatty acid counterparts using only water as co-reagent and with unparallelled selectivity. A multitude of Ohys has been described, however, direct comparison is hard due to the use of different assays. For this work, we characterized and compared four Ohys across different homologous families (HFams): those from Elizabethkingia meningoseptica (EmOhy, HFam11), Stenotrophomonas nitritireducens (SnOhy, HFam11), Rhodococcus erythropolis (ReOhy, HFam3), and Rhodococcus pyridinivorans (RpOhy, HFam2). All enzymes, especially SnOhy, expressed well in Escherichia coli (28-99 mg/Lculture). FAD occupancy after purification was 51% or lower for all Ohys. ReOhy had lost the flavin altogether, making supplementation a necessity for its activity. Reduction of the cofactor to FADH2 clearly showed a favorable effect on the activity of all Ohys, with product yields increasing from modest to 12-fold. Although SnOhy showed the highest initial reaction rates, EmOhy reached the highest 10-hydroxystearic acid (10-HSA) yields at higher oleic acid loading (10 mM) and prolonged reaction times. Thermostability was analyzed by thermal shift assays, with EmOhy appearing as most thermostable (Tm app = 54 °C).
Accurate differentiation between glioblastomas (GBM) and solitary brain metastases (MET) is crucial for treatment planning. This study evaluated the ability of amide proton transfer-weighted (APTw) MRI with and without fluid suppression (FS) to distinguish between GBM and MET. Thirty-two patients with histopathologically confirmed GBM (n = 24) or MET (n = 8) were included. Post-processing included creation of APTw maps without FS, with patient-specific FS based on the patient's white matter values and with a fixed-factor FS. Regions of interest (ROIs) were segmented in the contrast-enhanced tumour, peritumoural oedema, necrosis and the normal-appearing white matter (NAWM). The min, max and mean signals were extracted for each ROI and normalised to NAWM, creating normalised APTw (nAPTw) values. Group differences were determined with t test and Mann-Whitney U test. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. Both FS methods significantly reduced nAPTw values in tumour regions. Patient-specific FS showed highest performance in distinguishing GBM from MET in the necrotic (AUC 0.921) and oedematous regions (AUC 0.698). Fixed FS provided minor to intermediate improvements. Patient-specific fluid suppression increased the diagnostic performance of APTw imaging in differentiating GBM from MET, particularly in oedematous and necrotic regions.
In child sexual abuse trials, attorneys often use demonstrative anaphors, such as it, that, this, these, and those, to refer to children's earlier statements, questions, or portions of them. For example, after a child says, "He left the room," an attorney may ask, "What happened after that?" Here, that is an anaphor referring to the multi-word statement "He left the room." To answer such questions, children must identify the intended referent and retrieve the relevant information, increasing cognitive load and potentially leading to brief responses or misunderstanding. We examined how the anaphors it, that, this, these, and those shaped responses from 5- to 10-year-old children in 40 trial testimonies comprising 12,314 question-answer (Q-A) pairs. Prosecuting and defense attorneys frequently used anaphora, appearing in 30% of Q-A pairs. When anaphors replaced multi-word or compound referents rather than single-word referents, children's elaboration decreased. Contrary to expectations and prior studies, children elaborated more when a Q-A pair contained multiple anaphors. Elaboration and misunderstanding also increased when children, rather than attorneys, first introduced an anaphor. We conclude that those questioning children about sexual abuse should avoid using anaphora for multi-word or compound referents and promptly clarify any anaphoric referent to reduce misunderstanding or incomprehension.
Transcranial direct current stimulation (tDCS) on the prefrontal and posterior parietal cortex can enhance mental rotation (MR) performance, whereas little is known about cerebellar tDCS (ctDCS). This study aimed to evaluate effects of ctDCS on a MR task. Fifty-five healthy subjects were randomly assigned to active-ctDCS (1.5 mA; 20 min; n = 28) or sham-ctDCS (n = 27). Participants performed a MR task before (T0) and after (T1) stimulation. In each trial, two shapes appeared on a computer screen, one randomly rotated by 0, 45, 90, or 135 degrees. Subjects pressed the A or L key to indicate whether the shapes were identical or mirrored. A linear mixed model was run on the reaction times (RTs) recorded in each trial. Percent change in RTs (%RT) from T0 to T1 was also computed and analyzed using a second mixed-effects model with planned contrasts. A significant main effect of Time revealed RTs decreased from T0 (M = 3079.35, SE = 102.27) to T1 (M = 2565.36, SE = 102.27). No significant main effects or interactions involving Group were observed in either RT or %RT models. Planned contrasts revealed a single significant difference between groups in the 0° same condition, with the ctDCS group showing a greater reduction in %RT compared to the sham group. No other significant effects were found. ctDCS did not produce a global improvement in MR but showed selective effects under minimal spatial transformation demands. Further studies with different stimulation protocols are needed to clarify its role.
Aqueous zinc-iodine batteries (AZIBs) show promise for grid-scale energy storage, but they are hampered by polyiodide shuttling, sluggish iodine redox kinetics, and irreversible active-site poisoning caused by uncontrolled adsorption. We provide a comprehensive screening of M1 (M1 = P, S, B) heteroatom dopants, and P is identified as the best candidate for achieving coordination-tuned, moderate adsorption that balances adsorption and catalytic activity while mitigating site poisoning. Using phytic acid as both the P source and an etchant, we create a universal in situ approach to core-shell single-atom catalysts (M2-P-CSNC, M2 = Fe, Co, Ni). The unique core-shell structure achieves stable confinement of polyiodides, rapid ion transport, and protection of active sites, while in situ P doping precisely regulates the local electronic environment and d-band center of the Fe-Nx active centers. In situ characterization confirms that Fe-P-CSNC has a strong reversible anchoring ability for polyiodides, which can significantly accelerate redox kinetics. The optimized Fe-P-CSNC/I2 exhibits almost no capacity decay after 20,000 cycles at a current density of 2 A g-1. This work's facile heteroatom doping strategy for electronic modulation offers a reference for high-performance catalyst design in conversion-type energy storage systems. Kindly check and confirm the edit made in the title.1. We have checked and confirmed the edited title. 2. We found some issues with Figure 3d and have uploaded the revised image as an attachment.
Brief interventions delivered in healthcare settings represent a promising substance use prevention and early intervention strategy for youth in foster care, among whom early life adversity and resulting psychological sequalae increase risk for problematic substance use. Limited research has examined the effectiveness of brief interventions in this subpopulation. This study aimed to examine whether psychological diagnoses were associated with screening positive for problematic substance use, and whether psychological diagnoses impacted effectiveness of a brief intervention for substance use. Longitudinal observational study of adolescents (ages 10-20 years) seen for mandated health examinations in a foster care clinic. Youth who endorsed substance use and received a brief intervention were invited to complete baseline surveys and follow-ups at 30 days, 60 days and 6 months. Logistic regressions evaluated associations of mental health disorders with endorsing problematic substance use. Generalized linear mixed models examined associations of mental health disorders with trajectories of post-intervention change in substance use. Midwest, United States. Adolescents seen for mandated health examinations in a foster care clinic who completed a substance use screening measure [CRAFFT2.1 + N; n = 1656; mean age (SD) = 14.4 (2.6); 53.4% female; 58.4% Black, 31.6% white]. A second subsample included only those adolescents who received a brief intervention for substance use during their clinic visit [n = 287; mean age (SD) = 15.9 (2.1); 59.9% female; 53.7% Black, 35.5% white]. Mental health diagnoses and CRAFFT2.1 + N were extracted from the electronic health record. Youth-reported count of past 30-day use of alcohol, cannabis and nicotine/tobacco at each wave. A minority (12%) of youth in foster care endorsed problematic substance use. Youth with a mental health diagnosis had 58% to 161% higher odds of reporting problematic substance use [odds ratios (ORs) = 1.58-2.61; 95% confidence intervals (CIs) = (1.16-2.13) - (1.93-3.56)]. Following the intervention, youth who had been diagnosed with internalizing disorders (i.e. anxiety, depressive and trauma disorders), and those with co-occurring internalizing and externalizing disorders, reported smaller decreases or no decreases in their cannabis [ORs = 2.09, 7.03; 95% CIs = (1.17-3.71), (3.43-14.42)] and nicotine use [ORs = 1.95-7.68; 95% CIs = (1.08-3.53) - (4.12-14.32)]. Alcohol use did not vary as a function of mental health diagnoses [ORs = 0.31-13.10; 95% CIs = (0.00-19.37) - (0.19-915.80). Foster youth in the United States, particularly those with mental health concerns, appear to be at high risk for problematic substance use.
Anti-TNF and anti-IL-12/IL-23 are commonly used therapies for immune-mediated inflammatory diseases (IMIDs), including inflammatory bowel disease (IBD). Although several studies have shown intact T cell responses following 2 to 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in biologics treated IMID patients, our group previously reported increased waning of T cell responses at 3-4 mos following the second vaccine dose in IMID patients compared to healthy controls, raising the possibility that a suboptimal initial T cell response could impact long term immunity. Here, to reduce patient heterogeneity, we focused only on IBD patients and further investigated T cell responses in vaccinated, untreated and biologics treated IBD patients compared to healthy controls. Following 1 vaccine dose, we observed a decreased frequency of Spike-reactive Th1 polarized cells and an increased frequency of Th2 cells in the IBD patients in general, relative to healthy controls. Additionally, IBD patients exhibited increased waning of Spike-specific cytokine T cell responses after 2 doses of vaccine. We also observed IBD-treatment specific effects. Spike-specific IL-2 secretion from anti-TNF or anti-IL-12/IL-23-treated patients' T cells was lower than from untreated patients following 1 dose of vaccine. However, single-cell RNA-sequencing of Spike-responsive T cells from anti-TNF and anti-IL-12/IL-23 treated IBD patients and healthy controls 2-4 wk after 2 or 3 vaccine doses revealed no major differences in T cell subsets, transcriptomes or TCR diversity. Thus, despite some evidence of impaired primary T cell responses, Spike-reactive T cells in patients treated with anti-TNF or anti-IL-12/IL-23 appear indistinguishable from healthy controls following a full vaccine course.
Adolescence is a period in which appearance and relationships matter more than most. For those with visible differences, they can experience psychosocial challenges in their interactions with others. For young people with limb difference, it is unclear in the literature if they experience similar social challenges to their peers with other visible differences. The study aimed to understand the lived experience of young people with limb difference and explore the impact on their relationships and interactions with others. A qualitative design was used in which data was collected via semi-structured interviews with six young people with limb difference (aged 14-17 years) and analysed using interpretative phenomenological analysis (IPA). Three themes were developed [1]: 'functioning under the threat of others' intrigue' [2], 'being with others like me' [3], 'disability being seen over capability'. Findings demonstrate limb-different young people's perception of their appearance and ability is impacted by other people. Interacting with peers with limb difference can have a positive impact, whereas comments and assumptions from others can have a negative impact. Young people with visible difference can be at risk of psychosocial difficulties due to challenges with interactions with others.The findings demonstrated how the actions of others within social interactions can impact how a young person with limb difference perceives themselves, in terms of their appearance and ability.Rehabilitation professionals should facilitate peer support spaces for socialising with limb-different others as this is not universally available through paediatric healthcare at present.
Lower free testosterone (T) appears more strongly associated with male sexual dysfunction than total T, but most evidence is based on calculated free T (cFT) rather than measured free T (mFT). This study examined associations between mFT and sexual function in community-dwelling men. Cross-sectional analysis of 526 European Male Ageing Study participants. Sexual function was assessed by validated questionnaire. mFT was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) following equilibrium dialysis. Vermeulen-derived cFT was calculated from LC-MS/MS total T and sex-hormone binding globulin. Associations of sexual outcomes with total T, cFT and mFT were analysed using proportional ordinal logistic regression and restricted cubic splines adjusted for age, body mass index (BMI) and centre. Participants had a mean age 70.5 ± 8.5 years, BMI 27.3 ± 3.3 kg/m2, cFT 269.2 ± 86.6 pmol/L and mFT 198 ± 82 pmol/L. Lower mFT was significantly associated with erectile dysfunction (odds ratio (OR) per 10 pmol/L decrease 1.04[1.01-1.06]), fewer sexual intercourse (OR 1.03[1.00-1.06]), lower orgasm frequency (OR 1.03[1.01-1.06]) and reduced sexual desire (OR 1.03[1.01-1.05]). Total T was not associated with any outcome and cFT only with erectile dysfunction (OR 1.03[1.01-1.05]) and reduced sexual desire (OR 1.03[1.00-1.05]). Non-linear associations were observed for mFT with erectile function and orgasm frequency, with markedly steeper increase in predicted probability below 163 and 138 pmol/L, respectively. In community-dwelling men, lower mFT was associated with worse erectile function, fewer sexual intercourse attempts, reduced orgasm frequency, and lower sexual desire, with apparent non-linear thresholds for erectile dysfunction and orgasm frequency at 163 and 138 pmol/L, respectively.
Anorectal malformations are common congenital anomalies. Accurate preoperative imaging of fistulous connections is crucial for surgical planning. Traditional imaging uses ionizing radiation and often requires sedation. Contrast-enhanced colosonography, based on the application of ultrasound contrast agents, has been developed to overcome these limitations while still providing high-resolution structural information for the evaluation of anorectal malformations. The indications of laparoscopically assisted anorectoplasty for recto-bulbar urethral fistulas remain debated. This study aimed to evaluate the diagnostic accuracy of contrast-enhanced colosonography in detecting anorectal malformations and its value in guiding surgical approach selection. The diagnostic performance of preoperative contrast-enhanced colosonography and fluoroscopic colostography was compared in 72 cases, with surgical findings serving as the reference standard. Additionally, the relationship between surgical approach and the data from recto-urethral fistula was evaluated. Contrast-enhanced colosonography showed higher sensitivity for fistula detection rate than fluoroscopic colostography (98.6% vs. 83.3%, P<0.001). Concordance with surgical anatomy was 98.6% for contrast-enhanced colosonography, while 73.6% for fluoroscopic colostography. Among patients with recto-bulbar urethral fistula, a pouch-perineum (P-P) cutoff value of 23.5 mm (sensitivity 66.7%, specificity 76.0%) yielded an area under the curve of 0.747 (P=0.01, 95% CI 0.589-0.904). Contrast-enhanced colosonography appears to be a safe, effective, and versatile method for obtaining critical preoperative structural information in patients with anorectal malformations. For patients with recto-urethral fistulas, contrast-enhanced colosonography enables further differentiation between recto-membranous and recto-bulbar urethral fistulas. In specified cases, the P-P measurement may be helpful in selecting the appropriate surgical approach.
Pulsed field ablation (PFA) is a non-thermal energy modality for ablation of atrial fibrillation (AF). Although PFA has demonstrated an excellent overall safety profile, increasing evidence suggests an association with intravascular hemolysis, and acute kidney injury (AKI). However, the extent of hemolysis across different PFA catheters remains poorly characterized and warrants further investigation. We prospectively enrolled 239 patients undergoing AF ablation using the pentaspline (n = 107), balloon-in-basket (n = 71), or lattice-tip (n = 61) catheter. Laboratory markers of hemolysis, myocardial injury, renal function and haemoglobin were collected pre- and 24 h post-procedure. Significant haptoglobin depletion was observed exclusively with pentaspline, [pre 99.8 mg/dL (70.2-122) vs. post 55.7 mg/dL (23.2-91.8); p < 0.001] Reductions with the lattice-tip (p = 0.074) and the balloon-in-basket (p = 0.201) catheter did not reach statistical significance. AKI was only observed with the pentaspline catheter (pentaspline: 4.9%; balloon-in-basket: 0.0%; lattice tip: 0.0%; p = 0.020).Myocardial markers increased across all groups, but significantly higher in pentaspline and balloon-in-basket (p = n.s.) vs lattice-tip (p < 0.001 vs pentaspline, p < 0.001 vs ballon in basket). In this large cohort, contemporary PFA systems appear safe but catheter design influences the extent of hemolysis, AKI, and myocardial injury. The pentaspline catheter was associated with the greatest hemolytic effect and higher transient AKI, without clinically relevant reductions in hemoglobin or persistent renal impairment. Higher levels of myocardial injury in the pentaspline and balloon-in-basket groups correspond to the larger lesion footprints of these devices.Word counting abstract: 234.
Due to the excessive consumption of fossil fuels and the increasingly severe global environment, the world urgently needs to develop new clean and renewable energy sources. However, these energy sources have intermittency and instability, so it is necessary to vigorously develop efficient and large-scale energy conversion and storage technologies such as fuel cells, water electrolyzers, and metal-air batteries based on the core reactions of oxygen evolution reaction and oxygen reduction reaction. Because of their excellent molecular designability and structural tunability, covalent organic frameworks (COFs) show great potential for applications in this field. In this review, we first classify COF-based electrocatalysts based on the nature of active sites. Subsequently, strategies including structural design and functional synthesis for improving performance of COF-based electrocatalysts in the field of oxygen catalysis are systematically reviewed. Importantly, mechanism discussion of the performance improvement is highlighted. Finally, we put forward prospects for the future research directions, challenges, and development opportunities in this field. This review aims to provide guidance for the development of high-performance COF-based electrocatalysts through critical analysis of existing research, revealing the correlation between material design and mechanism for performance improvement.
Arthroscopic lysis and lavage of the temporomandibular joint (TMJ) is an established treatment for internal derangements (ID). Conventional techniques are limited to the superior compartment, although pathologies and translational movement frequently involve the inferior compartment. This prospective pilot case series describes and evaluates a reproducible needle-based arthroscopy-assisted technique for lysis and lavage of the inferior compartment, with no superior-compartment-only control group. Twenty patients with Wilkes stage IV anterior disc displacement without reduction and condylar resorption confirmed on MRI/CT were prospectively treated. Follow-up ranged from 12 to 24 months (mean 18.0 ± 5.2 months). Two 18G needles were introduced under arthroscopic guidance through the lateral discal transitional zone into the inferior compartment, enabling lavage with 100 mL of Ringer's solution. Superior compartment lysis and lavage were subsequently performed, followed by injection of high-molecular-weight hyaluronic acid. Outcomes included pain (Visual Analog Scale, VAS) and mandibular motion (maximum mouth opening and laterality). VAS scores (left side) decreased from 5.15 ± 3.00 preoperatively to 0.40 ± 0.99 postoperatively. VAS scores (right side) decreased from 4.65 ± 3.01 to 0.50 ± 0.76. Maximum mouth opening improved by + 4.25 ± 4.19 mm (95% CI 2.32-6.18). Right and left laterality improved by + 3.45 ± 2.89 mm and + 2.55 ± 2.31 mm, respectively, with 85-90% of patients showing increased excursions. No major complications occurred. This pilot series suggests that arthroscopy-assisted needle-based access to the inferior TMJ compartment appears feasible and safe, yielding clinically meaningful improvements in pain and motion. The technique is cost-effective and reproducible, and may expand minimally invasive therapeutic options for advanced internal derangements. Controlled comparative studies are required to establish its incremental benefit over superior compartment arthroscopy alone.
Sugammadex may interfere with serum progesterone immunoassays, potentially rendering measured concentrations and resulting recommendations unreliable. We investigated the effect of a range of sugammadex concentrations on serum progesterone concentrations in samples from pre-menopausal female volunteers. Samples were spiked with sugammadex concentrations (15-120 μM), corresponding to clinical doses between 2 mg.kg-1 and 19 mg.kg-1. Total progesterone concentrations in each sample were determined using the routine electrochemiluminescence immunoassay method. A subgroup of 15 samples underwent further testing using liquid chromatography-tandem mass spectroscopy, comparing baseline with sugammadex 120 μM. Thirty-five participants provided blood samples. Increasing concentrations of sugammadex were associated with lower measured serum progesterone, with an approximate 10% reduction with each doubling of sugammadex concentration (F(2,30) = 4.86, p = 0.015). Overall, progesterone concentrations decreased by a mean (SD) of 34.6% (12.4%) between control samples and those spiked with sugammadex 120 μM (p = 0.015). In contrast, liquid chromatography-tandem mass spectroscopy showed no statistically significant biochemical change in progesterone concentrations between baseline and sugammadex 120 μM. Sugammadex produced a dose-dependent reduction in the progesterone concentrations when measured by immunoassay techniques, but not by liquid chromatography-tandem mass spectroscopy. This suggests that an immunoassay interference occurs across clinically relevant doses. Progesterone results from routine laboratory testing should be interpreted with caution in the presence of sugammadex. We studied blood samples from 35 women to see whether a medicine called sugammadex affects progesterone test results. We added different amounts of sugammadex to the samples and then measured progesterone levels using a common hospital laboratory test. We also checked some samples using a second, more precise testing method. Progesterone is an important hormone, and doctors sometimes measure it to make decisions about a patient's health. There were concerns that sugammadex, a medicine often used after anaesthesia, might interfere with progesterone blood tests and make the results inaccurate. We wanted to find out if this was true. The usual laboratory test showed lower progesterone levels when more sugammadex was added to the blood samples. At the highest dose, progesterone appeared to be about one‐third lower than it really was. However, when the same samples were tested using a more accurate method, progesterone levels did not change. This suggests that sugammadex does not actually lower progesterone levels, but it can make some laboratory tests give misleading results. Doctors should therefore be careful when interpreting progesterone test results from patients who have recently received sugammadex.
To enhance lignocellulose degradation in tobacco stem fibers and improve the quality of reconstituted tobacco, this study optimized xylanase-mediated hydrolysis. Xylanase OKBK was identified as the most effective enzyme, producing a reducing sugar yield of 2.29%, significantly higher than those obtained with other tested enzymes (p< 0.05). Single-factor experiments were performed to evaluate the effects of six key parameters, including enzyme concentration, hydrolysis time, pH, solid-to-liquid ratio, temperature, and shaking speed. Plackett-Burman design identified five significant factors (p< 0.05), and the steepest ascent method was subsequently used to determine the optimal region for response surface optimization. A Box-Behnken design was then applied to develop a quadratic regression model involving temperature, hydrolysis time, and enzyme concentration, which exhibited high predictive accuracy (R²= 0.9950). The optimized conditions predicted by the model were 50 ℃, 4.5 h, and 400 U/mL, resulting in a reducing sugar yield of 21.1%, closely matching the predicted value of 21.5%. Component analysis, FTIR, and SEM characterization demonstrated that xylanase effectively disrupted the lignocellulosic structure and facilitated component degradation. Furthermore, sensory evaluation of reconstituted tobacco sheets prepared from enzymatically treated stems showed improved sensory properties, particularly reduced woody odor and smoke harshness. Overall, the optimized xylanase hydrolysis process enhanced lignocellulose degradation and sensory quality, providing a promising strategy for the high-value utilization of tobacco stem waste.
Hepatocellular carcinoma (HCC) responds poorly to immune checkpoint blockade, largely because of an immunologically cold tumor microenvironment (TME) characterized by deficient antigen presentation and impaired cytotoxic T cell responses. Analysis of numerous HCC clinical cohorts, including our institutional datasets, reveals that stimulator of interferon genes (STING) pathway activity is positively correlated with patient survival, enhanced antigen presentation capacity, and an immune-activated TME. However, achieving effective and controllable STING activation in immune-cold HCC tumors remains challenging. Here, we develop a biomimetic nanomedicine that integrates photothermal therapy (PTT), STING pathway activation, and immune checkpoint blockade to treat refractory HCC. A coordination nanomedicine MCI-NP is engineered by co-encapsulating the STING agonist MSA-2 and indocyanine green (ICG) via Cu2+-mediated chelation, enabling stabilized PTT-induced immunogenic cell death together with robust STING-driven innate immune activation. Further cloaked with PD-1-overexpressing cell membranes, MCI-NP@mPD-1 achieves an approximately fivefold increase in tumor accumulation compared with uncoated MCI-NP and enables localized PD-1/PD-L1 axis blockade. Following a single treatment, MCI-NP@mPD-1-based photothermal immunotherapy effectively suppresses primary tumor growth and significantly prolongs survival by remodeling the TME toward an immune-active state, while inducing durable systemic immune memory that effectively limited postoperative lung metastasis. Without introducing additional nanocarriers or excipients, MCI-NP@mPD-1 offers a promising therapeutic paradigm for photothermal immunotherapy of immune-cold HCC.
Professional values and moral resilience are recognized as essential attributes of nursing practice. In critical care settings, where nurses routinely face ethical complexity and high-stakes decisions, it is important to understand how these attributes shape professional competence. To examine the relationship between professional values and professional competence among critical care nurses, and to determine whether moral resilience mediates this relationship. This descriptive and correlational study was conducted among nurses working in the critical care units of six hospitals between August and October 2025. The reporting was conducted in accordance with the STROBE guidelines. Three validated instruments were used: a professional values scale (range 1-5, with higher scores indicating stronger professional values), a moral resilience scale (range 1-4, with higher scores indicating greater moral resilience) and a professional competence scale (range 1-5, with higher scores indicating greater professional competence). In total, 201 nurses participated in the study. Mean scores were high for professional values (4.45 ± 0.61 out of 5), moral resilience (3.27 ± 0.43 out of 4) and professional competence (4.26 ± 0.36 out of 5). Professional values were significantly and positively correlated with professional competence (r = 0.329, p < 0.001), whereas moral resilience showed no significant association with either variable. The direct effect of professional values on professional competence was significant (β = 0.193, p < 0.001), whereas the indirect effect through moral resilience was non-significant (β = 0.003, 95% CI [-0.005, 0.014]). Professional values appear to play an important role in promoting professional competence among critical care nurses, whereas moral resilience did not mediate this relationship. Strengthening ethics-based education and professional value development may enhance competence in critical care practice. Nurse educators and managers should prioritize the integration of professional values into nursing curricula, continuing professional development and clinical practice to strengthen professional competence among critical care nurses. Because moral resilience was not associated with competence, resilience-supporting initiatives may be directed primarily at nurses' well-being and retention rather than competence.
White spot syndrome virus (WSSV) represents one of the most severe threats to shrimp aquaculture worldwide, with no effective antiviral treatments currently available. In this study, the antiviral and antioxidant potential of the flavonoids amentoflavone, agathisflavone, and apigenin was investigated using an integrated in silico approach combining molecular docking, pharmacophore analysis, and Normal Mode Analysis (NMA)-based molecular dynamics. Docking simulations revealed that all flavonoids bind favorably to WSSV thymidylate synthase (wTS) and to the glutathione S-transferase from L. vannamei (LvGSTmu), with binding affinities superior to those of the co-crystallized ligands. Amentoflavone showed the highest affinity toward wTS, preserving key catalytic interactions and closely mimicking the binding mode of the native substrate. Pharmacophore analysis highlighted the importance of aromatic centers and hydrogen bond donor/acceptor groups in stabilizing ligand-protein complexes. NMA-based dynamics demonstrated that amentoflavone and apigenin confer increased structural stability to wTS and LvGSTmu, respectively, reducing conformational fluctuations without compromising protein integrity. Molecular dynamics simulations confirmed the stability of the complexes throughout the 200 ns simulation, while MM/GBSA analysis revealed favorable binding free energies, supporting stable interactions with wTS. Overall, these results suggest that flavonoids, particularly amentoflavone, represent promising scaffolds for the development of antiviral and antioxidant agents against WSSV, warranting further experimental validation.