Predicting the efficiency of arsenic immobilization in soils by biochar using machine learning.

Arsenic (As) pollution in soils is a pervasive environmental issue. Biochar immobilization offers a promising solution for addressing soil As contamination. The efficiency of biochar in immobilizing As in soils primarily hinges on the characteristics of both the soil and the biochar. However, the influence of a specific property on As immobilization varies among different studies, and the development and application of arsenic passivation materials based on biochar often rely on empirical knowledge. To enhance immobilization efficiency and reduce labor and time costs, a machine learning (ML) model was employed to predict As immobilization efficiency before biochar application. In this study, we collected a dataset comprising 182 data points on As immobilization efficiency from 17 publications to construct three ML models. The results demonstrated that the random forest (RF) model outperformed gradient boost regression tree and support vector regression models in predictive performance. Relative importance analysis and partial dependence plots based on the RF model were conducted to identify the most crucial factors influencing As immobilization. These findings highlighted the significant roles of biochar application time and biochar pH in As immobilization efficiency in soils. Furthermore, the study revealed that Fe-modified biochar exhibited a substantial improvement in As immobilization. These insights can facilitate targeted biochar property design and optimization of biochar application conditions to enhance As immobilization efficiency.

Robust Natural Light-Absorbable and -Degradable AIE Photosensitizers for Fluorescence Labeling and Efficient Photodynamic Eradication of Algal Pollutants.

Current water pollution caused by the excessive proliferation of harmful algae urges green methods that can efficiently utilize natural light to treat algal pollution. Herein, a series of aggregation-induced emission (AIE) photosensitizers that can efficiently harness sunshine were synthesized for the environmentally friendly and biocompatible treatment of algal pollution. By tuning the number of thiophene units and the electron conjugation degree, the photosensitizers' absorptions were broadened to cover the whole visible light range. The positive charges guided photosensitizers to aggregate on algal cell surfaces, resulting in a turn-on fluorescence signal and robust reactive oxygen species generation under sunshine, thereby achieving fluorescence labeling and photodynamic eradication of algae. The eradication outcomes demonstrated that the AIE photosensitizers significantly outperformed the commercial algaecide ALG. At 20 ppm photosensitizers, 90.4% and 94.2% killing rates were achieved for C. reinhardtii and C. vulgaris, respectively, 2.8- and 3.6-fold higher than those from the same concentration of ALG. Excellent performances in inhibiting algae growth were also verified with efficiency superior to that of ALG. Importantly, the photosensitizers can self-degrade into biocompatible fragments under irradiation to avoid secondary pollution. The developed photosensitizers that possess sunshine convertibility and degradability provide an efficient tool for algal treatment, showing broad research and application prospects.

N6-methyladenosine modification-tuned lipid metabolism controls skin immune homeostasis via regulating neutrophil chemotaxis.

Disrupted N6-methyladenosine (m6A) modification modulates various inflammatory disorders. However, the role of m6A in regulating cutaneous inflammation remains elusive. Here, we reveal that the m6A and its methyltransferase METTL3 are down-regulated in keratinocytes in inflammatory skin diseases. Inducible deletion of Mettl3 in murine keratinocytes results in spontaneous skin inflammation and increases susceptibility to cutaneous inflammation with activation of neutrophil recruitment. Therapeutically, restoration of m6A alleviates the disease phenotypes in mice and suppresses inflammation in human biopsy specimens. We support a model in which m6A modification stabilizes the mRNA of the lipid-metabolizing enzyme ELOVL6 via the m6A reader IGF2BP3, leading to a rewiring of fatty acid metabolism with a reduction in palmitic acid accumulation and, consequently, suppressing neutrophil chemotaxis in cutaneous inflammation. Our findings highlight a previously unrecognized epithelial-intrinsic m6A modification-lipid metabolism pathway that is essential for maintaining epidermal and immune homeostasis and lay the basis for potential therapeutic targeting of m6A modulators to attenuate inflammatory skin diseases.

PerturBase: a comprehensive database for single-cell perturbation data analysis and visualization.

Single-cell perturbation (scPerturbation) sequencing techniques, represented by single-cell genetic perturbation (e.g. Perturb-seq) and single-cell chemical perturbation (e.g. sci-Plex), result from the integration of single-cell toolkits with conventional bulk screening methods. These innovative sequencing techniques empower researchers to dissect perturbation effects in biological systems at an unprecedented resolution. Despite these advancements, a notable gap exists in the availability of a dedicated database for exploring scPerturbation data. To address this gap, we present PerturBase, the most comprehensive database designed for the analysis and visualization of scPerturbation data (http://www.perturbase.cn/). PerturBase curates 122 datasets from 46 publicly available studies, covering 115 single-modal and 7 multi-modal datasets that include 24 254 genetic and 230 chemical perturbations from approximately 5 million cells. The database, comprising the 'Dataset' and 'Perturbation' modules, provides insights into various results, encompassing quality control, denoising, differential gene expression analysis, functional analysis of perturbation effects and characterization of relationships between perturbations. All the datasets and results are presented on user-friendly, easy-to-browse web pages and can be visualized through intuitive and interactive plot and table formats. In summary, PerturBase stands as a pioneering, high-content database intended for searching, visualizing and analyzing scPerturbation datasets, contributing to a deeper understanding of perturbation effects.

Synergistic Potential of Nanomedicine in Prostate Cancer Immunotherapy: Breakthroughs and Prospects.

Given the global prevalence of prostate cancer in men, it is crucial to explore more effective treatment strategies. Recently, immunotherapy has emerged as a promising cancer treatment due to its unique mechanism of action and potential long-term effectiveness. However, its limited efficacy in prostate cancer has prompted renewed interest in developing strategies to improve immunotherapy outcomes. Nanomedicine offers a novel perspective on cancer treatment with its unique size effects and surface properties. By employing targeted delivery, controlled release, and enhanced immunogenicity, nanoparticles can be synergized with nanomedicine platforms to amplify the effectiveness of immunotherapy in treating prostate cancer. Simultaneously, nanotechnology can address the limitations of immunotherapy and the challenges of immune escape and tumor microenvironment regulation. Additionally, the synergistic effects of combining nanomedicine with other therapies offer promising clinical outcomes. Innovative applications of nanomedicine include smart nanocarriers, stimulus-responsive systems, and precision medicine approaches to overcome translational obstacles in prostate cancer immunotherapy. This review highlights the transformative potential of nanomedicine in enhancing prostate cancer immunotherapy and emphasizes the need for interdisciplinary collaboration to drive research and clinical applications forward.

Endovascular Management of Non-Cirrhotic Acute Portomesenteric Venous Thrombosis.

Acute portomesenteric venous thrombosis (PVT) is a rare but potentially life-threatening condition in individuals without cirrhosis. Initial management typically involves anticoagulation therapy, but the optimal approach to interventional treatment remains a topic of ongoing research. This article explores both traditional and emerging endovascular techniques, providing an overview of the existing evidence supporting their use. Additionally, it delves into the significance of acute PVT in the context of contemporary pathologies, notably COVID-19 infection, vaccine-induced immune thrombotic thrombocytopenia, and liver transplantation.

Spontaneous parametric downconversion in a laser-poled lithium niobate nonlinear photonic crystal with nanoscale resolution.

Based on quasi-phase-matching (QPM) theory, nonlinear photonic crystals (NPCs) are capable of realizing efficient spontaneous parametric downconversion (SPDC) for the generation of photonic entangled states. However, the traditional electric field poling techniques employed in NPC fabrication often result in non-negligible processing errors of a few hundred nanometers, thus impeding the production of quantum photon pairs as intended. In this work, we investigate the SPDC photon pairs generated in a laser-poled lithium niobate (LN) NPC. By using the recently developed laser poling technique, the processing error of the NPC is substantially reduced to approximately 15 nm. Consequently, the coincidence counts of the generated photon pairs in the experiment reach 83.6% of the designed value. Our result paves the way for on-demand production of high-quality quantum sources, which has potential applications in quantum communications and quantum computations.

Inhibition of acid-sensing receptor GPR4 attenuates neuronal ferroptosis via RhoA/YAP signaling in a rat model of subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is a devastating stroke, in which acidosis is one of detrimental complications. The extracellular pH reduction can activate G protein-coupled receptor 4 (GPR4) in the brain. Yet, the extent to which proton-activated GPR4 contributes to the early brain injury (EBI) post-SAH remains largely unexplored. Ferroptosis, iron-dependent programmed cell death, has recently been shown to contribute to EBI. We aimed to investigate the effects of GPR4 inhibition on neurological deficits and neuronal ferroptosis after SAH in rats. METHODS: A total 253 Sprague Dawley (SD) male rats (weighing 275-330g) were utilized in this study. SAH was induced by endovascular perforation. NE-52-QQ57 (NE), a selective antagonist of GPR4 was administered intraperitoneally 1-hour post-SAH. To explore the mechanisms, RhoA activator U-46619 and YAP activator PY-60 were delivered intracerebroventricularly. Short- and long-term neurobehavior, SAH grading, western blot assay, ELISA assay, immunofluorescence staining, and transmission electron microscopy was performed post-SAH. RESULTS: Following SAH, there was an upregulation of GPR4 expression in neurons. GPR4 inhibition by NE improved both short-term and long-term neurological outcomes post-SAH. NE also reduced neuronal ferroptosis, as evidenced by decreased lipid peroxidation products 4HNE and MDA levels in brain tissues, and reduced mitochondrial shrinkage, increased mitochondria crista and decreased membrane density. The application of either U-46619 or PY-60 partially offset the neuroprotective effects of NE on neuronal ferroptosis in SAH rats. CONCLUSIONS: This study demonstrated that acid-sensing receptor GPR4 contributed to neuronal ferroptosis after SAH via RhoA/YAP pathway, and NE may be a potential therapeutic strategy to attenuate GPR4 mediated neuronal ferroptosis and EBI after SAH.

The relationship of pain catastrophizing in principal caregivers of postoperative children with malignant bone tumors and children's kinesiophobia and pain perception: A cross-sectional survey.

OBJECTIVE: To examine the phenomenon of pain catastrophizing among the principal caregivers of postoperative children with malignant bone tumors and explore its impact on pain perception and kinesiophobia in children. DESIGN: A cross-sectional study design. METHODS: Using a cross-sectional study design, a questionnaire-based survey was conducted among 140 children with malignant bone tumors and their principal caregivers, who were admitted to a tertiary hospital in Shanghai from 2020 to 2023. Pearson's univariate and multiple regression analyses were conducted. The questionnaire included general data, the Parental Pain Catastrophizing Scale, the Short-Form McGill Pain Questionnaire, and the Tampa Scale of Kinesiophobia. RESULTS: The frequency of pain catastrophizing for the principal caregivers was 16.8%. The frequency of kinesiophobia in children was 93.1%. The level of pain catastrophizing was positively correlated with the level of kinesiophobia and pain perception (r = 0.556, 0.614, p < 0.05). Multiple logistic regression analysis showed that the level of pain catastrophizing in principal caregivers was an important factor of kinesiophobia in children (B = 0.370, Std. = 0.119, Wald = 9.687, Ex (P) = 1.448, p = 0.002). Multiple linear regression analysis showed that the incidence of pain catastrophizing and the level of kinesiophobia were important influencing factors in pain perception (p < 0.05), with R2 = 0.272, adjusted R2 = 0.249, F = 11.579, and p < 0.001. CONCLUSIONS: The level of pain catastrophizing in the principal caregivers was an important factor in postoperative kinesiophobia and pain perception in children with a malignant bone tumor. PRACTICE IMPLICATIONS: It is important to evaluate the patients' and their families' emotional changes and psychological needs during the perioperative period. Nurses play a crucial role in providing appropriate interventions for patients or families to reduce the negative pain experience and improve patients' prognosis.

Utility of overnight oximetry indices in the evaluation of children with snoring and suspected obstructive sleep apnea.

STUDY OBJECTIVES: Optimal cutoff values of oximetry indices that differentiate obstructive sleep apnea (OSA) from primary snoring (PS) is not well established. Our study aimed to assess the utility of overnight oximetry indices in differentiating PS from OSA and assessing OSA severity, compared to polysomnography (PSG), in children with suspected OSA. METHODS: This was a retrospective study of children (1-18 years) with snoring who underwent PSG. Patients with Down syndrome, craniofacial anomalies, known genetic syndromes, neuromuscular conditions and central apnea index ≥ 5 were excluded. Demographic data, PSG variables and oximetry indices (e.g. oxygen desaturation index [ODI3, defined as number of ≥ 3% desaturation episodes/hour of artifact free recording time and SpO2 nadir]) were collected. RESULTS: Of 1,203 children (mean age 9.1±3.9 years, 67.7% males), 91.8% (847/923) ≤ 12 years and 84.3% (236/280) > 12 years had OSA. Optimal cutoff of ODI3 for differentiating PS from OSA was 2.4 [Se: 78.8% (75.9%-81.6%), Sp: 80.5% (69.9%-88.7%)] in ≤ 12 years and 3.6 [Se: 71.1% (64.8%-76.8%), Sp: 91.1% (78.8%-97.5%)] in > 12 years. The optimal cutoff of ODI3 for differentiating PS from mild, moderate and severe OSA categories were 2.0 [Se: 70.1% (65.3%-74.5%), Sp: 70.1% (58.6%-80.0%)]; 3.7 [Se: 82.3% (76.6%-87.1%), Sp: 94.8% (87.2%-98.6%)] and 4.3 [Se: 99.1% (96.8%-99.9%), Sp: 98.7% (93.0%-100.0%)] in ≤ 12 years; and 1.9 [Se: 78.8% (75.9%-81.6%), Sp: 80.5% (69.9%-88.7%)]; 4.1 [Se: 85.4% (72.2%-93.9%), Sp: 91.1% (78.8%-97.5%)] and 6.9 [Se: 98.4% (91.2%-100.0%), Sp: 97.8% (88.2%-99.9%)] in > 12 years, respectively. CONCLUSIONS: This study provides optimal cutoff values for ODI3 in differentiating PS from OSA and assessing OSA severity in children. As oximetry is cheaper and widely available, ODI3 has the potential to be incorporated into cost-effective clinical decision-making algorithms, especially in resource limited settings.

Gibberellin 2-oxidase 1(CsGA2ox1) involved gibberellin biosynthesis regulates sprouting time in camellia sinensis.

BACKGROUND: Tea is an important cash crop and buds are its main product. To elucidate the molecular mechanism of the sprouting time of tea plants, 'Yuchunzao', which was an early sprouting tea cultivar, was studied. 'Echa 1', sprout one week later than 'Yuchunzao' in spring, was used as the control. RESULTS: A total of 26 hormonal compounds and its derivatives in tea plants were qualified by using Ultra Performance Liquid Chromatography-Tandem mass spectrometry (UPLC-MS/MS). The result showed that GA20, GA3 and ICA were significantly different in 'Yuchunzao' than in 'Echa 1', with GA20 and GA3 up-regulated and ICA down-regulated. Based on the Illumina platform, transcriptome analysis revealed a total of 5,395 differentially expressed genes (DEGs). A diterpenoid biosynthesis related gene, gibberellin 2-oxidase 1 (CsGA2ox1), was downregulated in 'Yuchunzao' compared to 'Echa 1'. CsGA2ox1 regulate the transformation of GA different forms in plants. The relative expression of CsGA2ox1 showed an adverse trend with the content of GA20 and GA3. Our results suggest that down regulation of CsGA2ox1 resulted in the accumulation of GA3 and GA20, and then promoted sprout of 'Yuchunzao'. CONCLUSION: This study provides theoretical basis of tea plants sprout and guides the tea breeding in practice.

Imaging body-mind crosstalk in young adults.

Objective: There is evidence that complex relationships exist between motor functions, brain structure, and cognitive functions, particularly in the aging population. However, whether such relationships observed in older adults could extend to other age groups (e.g., younger adults) remains to be elucidated. Thus, the current study addressed this gap in the literature by investigating potential associations between motor functions, brain structure, and cognitive functions in a large cohort of young adults. Methods: In the current study, data from 910 participants (22-35 yr) were retrieved from the Human Connectome Project. Interactions between motor functions (i.e., cardiorespiratory fitness, gait speed, hand dexterity, and handgrip strength), brain structure (i.e., cortical thickness, surface area, and subcortical volumes), and cognitive functions were examined using linear mixed-effects models and mediation analyses. The performance of different machine-learning classifiers to discriminate young adults at three different levels (related to each motor function) was compared. Results: Cardiorespiratory fitness and hand dexterity were positively associated with fluid and crystallized intelligence in young adults, whereas gait speed and handgrip strength were correlated with specific measures of fluid intelligence (e.g., inhibitory control, flexibility, sustained attention, and spatial orientation; false discovery rate [FDR] corrected, p < 0.05). The relationships between cardiorespiratory fitness and domains of cognitive function were mediated by surface area and cortical volume in regions involved in the default mode, sensorimotor, and limbic networks (FDR corrected, p < 0.05). Associations between handgrip strength and fluid intelligence were mediated by surface area and volume in regions involved in the salience and limbic networks (FDR corrected, p < 0.05). Four machine-learning classifiers with feature importance ranking were built to discriminate young adults with different levels of cardiorespiratory fitness (random forest), gait speed, hand dexterity (support vector machine with the radial kernel), and handgrip strength (artificial neural network). Conclusions: In summary, similar to observations in older adults, the current study provides empirical evidence (i) that motor functions in young adults are positively related to specific measures of cognitive functions, and (ii) that such relationships are at least partially mediated by distinct brain structures. Furthermore, our analyses suggest that machine-learning classifier has a promising potential to be used as a classification tool and decision support for identifying populations with below-average motor and cognitive functions.

Real-world large sample assessment of drug-related dry eye risk: Based on the FDA adverse event reporting system database.

PURPOSE AND DESIGN: This study aimed to evaluate the risk of drug-related dry eye using real-world data, underscoring the significance of tracing pharmacological etiology for distinct clinical types of dry eye. METHODS: Analyzing adverse event reports in the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to September 2023, we employed disproportionality analysis and the Bayesian confidence propagation neural network algorithm. The analysis involved categorizing drugs causing dry eye, assessing risk levels, and conducting segmental assessments based on the time of onset of drug-related dry eye adverse reactions. RESULTS: In the FAERS database, adverse reactions related to dry eye were linked to 1160 drugs. Disproportionality analysis identified 33 drugs with significant risk, notably in ophthalmic (brimonidine, bimatoprost), oncology (tisotumab vedotin, erdafitinib), and other medications (isotretinoin, oxymetazoline). The top three drugs with the highest risk of drug-related dry eye are isotretinoin (Bayesian confidence propagation neural network (BCPNN) = 6.88), tisotumab vedotin (BCPNN = 6.88), and brimonidine (BCPNN = 6.77). Among different categories of drugs, respiratory medications have the shortest mean onset time for drug-related dry eye, averaging 50.99 days. The prevalence skewed towards females (69.9 %), particularly in menopausal and elderly individuals (45-70 years old, mean age 54.7 ± 18.2). Reports of drug-related dry eye adverse reactions showed an annual increase. CONCLUSION: Informed clinical decision-making is crucial for preventing drug-related dry eye. Assessing the risk of dry eyes associated with both local and systemic medications helps optimize treatment and provide necessary cautionary information.

The effect of predictive nursing on the mental state, compliance and sleep quality of senile cervicitis: An observational study.

To explore the effect of predictive nursing on the mental state, compliance and sleep quality of elderly patients with cervicitis. The clinical data of 96 elderly patients with cervicitis who were admitted to our hospital from June 2019 to June 2021 were selected as the research objects. According to the different treatments, they were divided into a control group and an observation group with 48 cases each. Among them, the control group was given routine care, and the observation group was given predictive care on the basis of the control group. The effects of the quality of life, mental state, compliance and sleep quality of the 2 groups of patients before and after nursing were compared. Comparing the nursing compliance of the 2 groups of elderly patients with cervicitis, statistics showed that the difference was statistically significant (P < .05). After nursing, the sleep quality, increased arousal, unstable sleep, and night terrors of the 2 groups of elderly patients with cervicitis were significantly improved, and the negative emotion score of the observation group was significantly lower than that of the control group. Statistics show that this difference is statistically significant (P < .05). The comparison of the quality of life scores of the 2 groups of patients before nursing was not statistically significant (P > .05). After nursing, the mental vitality score, social interaction score, emotional restriction score, and mental status of the observation group were significantly higher than those of the control group. Statistics showed that the difference was statistically significant (P < .05). After nursing, the psychological pressure of the 2 groups of elderly patients with cervicitis was significantly improved, and the observation group fear, anxiety, desire for knowledge, fear of discrimination, despair, and low self-esteem were significantly lower than those of the control group. The difference was statistically significant (P < .05). Predictive nursing can effectively improve the quality of life and sleep of elderly patients with cervicitis, reduce psychological pressure, improve compliance and sleep quality, and benefit the prognosis and clinical treatment of patients. It has a certain reference value for the nursing of elderly patients with cervicitis.

Drug-Related Keratitis: A Real-World FDA Adverse Event Reporting System Database Study.

Purpose: This study aimed to assess the drug risk of drug-related keratitis and track the epidemiological characteristics of drug-related keratitis. Methods: This study analyzed data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from January 2004 to December 2023. A disproportionality analysis was conducted to assess drug-related keratitis with positive signals, and drugs were classified and assessed with regard to their drug-induced timing and risk of drug-related keratitis. Results: A total of 1606 drugs were reported to pose a risk of drug-related keratitis in the FAERS database, and, after disproportionality analysis and screening, 17 drugs were found to significantly increase the risk of drug-related keratitis. Among them, seven were ophthalmic medications, including dorzolamide (reporting odds ratio [ROR] = 3695.82), travoprost (ROR = 2287.27), and brimonidine (ROR = 2118.52), and 10 were non-ophthalmic medications, including tralokinumab (ROR = 2609.12), trazodone (ROR = 2377.07), and belantamab mafodotin (ROR = 680.28). The top three drugs having the highest risk of drug-related keratitis were dorzolamide (Bayesian confidence propagation neural network [BCPNN] = 11.71), trazodone (BCPNN = 11.11), and tralokinumab (BCPNN = 11.08). The drug-induced times for non-ophthalmic medications were significantly shorter than those for ophthalmic medications (mean days, 141.02 vs. 321.96, respectively; P < 0.001). The incidence of drug-related keratitis reached its peak in 2023. Conclusions: Prevention of drug-related keratitis is more important than treatment. Identifying the specific risks and timing of drug-induced keratitis can support the development of preventive measures. Translational Relevance: Identifying the specific drugs related to medication-related keratitis is of significant importance for drug vigilance in the occurrence of drug-related keratitis.

Relieving effect of jiao-tune of 5-element music on negative emotions in patients with decompensated hepatitis B virus cirrhosis: A randomized and controlled experiment study.

BACKGROUND: Depression and anxiety are common in patients with decompensated hepatitis B virus (HBV) cirrhosis. This study aimed to evaluate the relieving effects of the jiao-tune of 5-element music on negative emotions in patients with decompensated HBV cirrhosis. METHODS: The patients were randomly allocated into the control group (standard nursing care) and the jiao-tune group (standard nursing care plus a 2-month course of music therapy with the jiao-tune of 5-element music). The negative emotions of patients were assessed before intervention treatment and at the end of the 2-month follow-up using the Zung Self-Rating Depression Scale (SDS) and Zung Self-Rating Anxiety Scale (SAS). RESULTS: The analysis included 209 patients, with 102 in the control group and 107 in the jiao-tune group, all of whom returned their completed questionnaires. Baseline clinical characteristics and length of hospital stay were comparable between 2 groups. Before intervention treatment, there were no significant differences in SAS score (55.78 ±â€…5.64 vs 56.47 ±â€…3.28) and SDS score (65.13 ±â€…3.12 vs 64.48 ±â€…4.47) between the jiao-tune group and control group. After 2-month follow-up, the jiao-tune group had a significantly lower SAS score (53.17 ±â€…5.61) and SDS score (61.28 ±â€…1.52) compared with the control group (55.49 ±â€…3.37 and 63.08 ±â€…2.76), there were significant differences between 2 groups (P < .001). CONCLUSIONS: The jiao-tune of 5-element music can relieve the negative emotions in patients with decompensated HBV cirrhosis.

Genicular Artery Embolization, Radiofrequency Ablation, and Corticosteroid Therapy for Knee Osteoarthritis: A Cost-Effectiveness Analysis Using Randomized Clinical Trial Data.

Background: Many patients with symptomatic knee osteoarthritis (KOA) are refractory to traditional nonsurgical treatments such as intraarticular corticosteroid (CS) injection but are not yet eligible for or decline surgery. Genicular artery embolization (GAE) and radiofrequency ablation (RFA) are emerging adjunctive or alternative minimally invasive treatments. Objective: To perform a cost-effectiveness analysis (CEA) comparing CS, GAE, and RFA, for treatment of symptomatic KOA using a Markov model based on a de novo network meta-analysis (NMA) of randomized control trials. Methods: CEA was conducted to compare GAE and RFA to CS using a Markov cohort state-transition model from a U.S. Medicare payer's perspective over a 4-year time horizon. The model incorporated each treatment's success and attrition rates, costs, and utility benefit. Utility benefit values were derived at short-term (0.5-3 months) and long-term (6-12 months) posttreatment follow-up from NMA of published RCTs using an outcome of improved knee pain and/or function. Analyses were conducted at a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY). Sensitivity analyses were performed, including when simulating various cost setting scenarios (i.e., office vs hospital outpatient treatment). Results: RFA demonstrated larger treatment effect than GAE, more pronounced at short-term [standardized mean difference (SMD), -1.6688, 95% CI [-2.7806; -0.5571], p=.003] than long-term (SMD -0.3822, 95% CI [-1.9743; 1.2100], p=.64) follow-up. Across cost setting scenarios, incremental cost-effectiveness ratios relative to CS were $561-1563/QALY for GAE versus $76-429/QALY for RFA (not counting scenarios in which RFA was dominated by CS). GAE demonstrated higher cost-effectiveness probability compared to RFA (41.6-54.8% vs. 18.4-29.2%, respectively). GAE was more cost-effective than RFA when the GAE clinical success rate and post-GAE utility value exceeded 32.1-51.0% and 0.562-0.617, respectively, and when the GAE quarterly attrition rate was less than 8.8-17.4%. RFA was more cost-effective when baseline pre-treatment utility values exceeded 0.695-0.713. Neither GAE costs nor RFA costs were sensitive parameters. Conclusion: Across scenarios, GAE was consistently the most likely cost-effective treatment option compared to RFA and CS, although clinical success rates, attrition rates, and utility values impact its cost-effectiveness. Clinical Impact: GAE is likely to be more cost-effective than RFA or CS for treatment of symptomatic KOA.

Psychometric validation of the Chinese version of the dry eye-related quality-of-life score questionnaire.

AIM: To psychometrically validate the Chinese version of the dry eye-related quality-of-life score questionnaire (DEQS-CHN) among Chinese patients with dry eye. METHODS: This study involved 231 participants, including 191 with dry eye disease (DED) comprising the dry eye disease group, and 40 healthy participants forming the control group. Participants were required to complete the DEQS-CHN, and Chinese dry eye questionnaire and undergo clinical tests including the fluorescein breakup time (FBUT), corneal fluorescein staining (CFS), and Schirmer I test. To assess the internal consistency and retest reliability, Cronbach's α and the intraclass correlation coefficient (ICC) were employed. Content validity was assessed by item-level content validity index (ICV) and an average scale-level content validity index (S-CVI/Ave). Construct validity was assessed by confirmatory factor analysis. The concurrent validity was assessed by calculating correlations between DEQS-CHN and Chinese dry eye questionnaire. Discriminative validity was evaluated through non-parametric tests, with receiver operating characteristic (ROC) curve serving as conclusive indicators of the questionnaire's distinguishing capability. RESULTS: The Cronbach's α coefficients for frequency and degree of ocular symptoms, impact on daily life, and summary score were 0.736, 0.704, 0.811, 0.818, 0.861, and 0.860, respectively, and the ICC were 0.611, 0.677, 0.715, 0.769, 0.711, and 0.779, respectively. All I-CVI scores ranged from 0.833 to 1.000, with an S-CVI/Ave of 0.956. Confirmatory factor analysis results exhibited a well-fitting model consistent with the original questionnaire [χ 2/df=2.653, incremental fit index (IFI)=0.924, comparative fit index (CFI)=0.924, Tucker-Lewis index (TLI)=0.909, and root mean square error of approximation (RMSEA)=0.065]. There was a moderate positive correlation between the DEQS-CHN and the Chinese dry eye questionnaire (r 2=0.588). The dry eye group demonstrated significantly higher scores compared to the control group, and the area under the curve (AUC) value was 0.8092. CONCLUSION: The DEQS-CHN has been demonstrated as a valid and reliable instrument for assessing the impact of dry eye disease on the quality of life among Chinese individuals with DED.

Epidemiology, survival and new treatment modalities for intrahepatic cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (iCCA) is a rare biliary tract cancer with increasing incidence and poor survival rates. This study aims to evaluate the incidence and survival trends of iCCA patients over 20 years using a national cancer database, and assess the temporal association between survival and landmark clinical trials. Methods: Data was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Age-adjusted incidence rates (AAIRs) were calculated from 2000 to 2020. Overall survival was analyzed based on diagnosis time and disease stage. Subgroup analysis was performed for patients diagnosed between 2015 and 2020. Landmark clinical trials were reviewed to determine temporal changes in survival. Results: In this analysis of 28,918 iCCA patients, the AAIR increased from 0.49 per 100,000 in 2000 to 1.38 in 2020 [annual percent change (APC) 6.94, 95% confidence interval (CI): 6.32 to 7.56], with a notable decline from 2019 to 2020. Incidence rates overall displayed an uptrend course across subgroups divided by sex, race, age, and disease stage. The age-adjusted median overall survival (mOS) improved from 5.28 months in 2000 to 9.3 months in 2013, then stabilized between 8.0-9.0 months after 2013. Using 2010 as a cutoff, when the ABC-02 trial was published, the decade-based mOS increased from 6.55 months in 2000-2010 to 9.06 months in 2010-2020. During 2015-2020, the overall mOS was 8.8 months, with mOS of 24.3, 12.1, and 5.4 months for local, regional, and distant stages, respectively. Conclusions: The study indicates a steady rise in iCCA incidence since 2000 across all subgroups. Survival rates improved since 2000 but stabilized after 2013, following the ABC-02 trial publication in 2010. The impact of more recent clinical trials on survival rates requires further analysis in the coming years.