The reliability and validity of triage tools in geriatric emergency departments: A scoping review.

BACKGROUND: The nurse's ability to accurately identify urgent conditions and triage this vulnerable population tends to be complex and challenging. Little is known about the reliability and validity of common triage tools in geriatric patients. AIM: To determine the reliability and validity of triage tools in geriatric emergency care and summarize the specific content of current triage tools for geriatric patients. METHODS: The eligible literature was searched from the MEDLINE, CINAHL, EMBASE, and Cochrane Database using targeted search strategies. We defined the objectives and questions, set standards for article inclusion criteria, and conducted literature searching and screening. The mixed methods assessment tool (MMAT) appraised the article's quality. Finally, we extracted and analyzed the data from the included articles, summarizing the results. Endnote X9 was used for data extraction and collation. RESULTS: Nine articles were eligible. These included six triage tools: CTAS, JTAS, KTAS, MTS, SETS, and ESI. The reliability of the CTAS was good when applied to triage geriatric patients. The SETS performed well in prehospital simulated triage. The ESI has moderate to excellent reliability. The CTAS has good to excellent validity, while the JTAS, KTAS, MTS, and ESI have fair to good results. CONCLUSION: Several triage tools are useful in geriatrics, but the reliability and validity of these tools have mixed results. Applying triage tools to triage geriatric patients still has limitations.

Preclinical Evaluation of a Radiolabeled Pan-RAF Inhibitor for RAF-Specific PET/CT Imaging.

Abnormalities in the RAS-RAF signaling pathway occur in many solid tumors, leading to aberrant tumor proliferation, invasion, and metastasis. Due to the elusive pharmacology of RAS, RAF inhibitors have become the main targeted therapeutic drugs. Naporafenib (LXH-254) is a high-affinity pan-RAF inhibitor with FDA Fast Track Qualification. We sought to develop an 18F-labeled molecular probe from LXH-254 for PET imaging of tumors overexpressing RAF to noninvasively screen patients for susceptibility to targeted RAF therapy. To reduce the lipid solubility, LXH-254 was designed with triethylene glycol di(p-toluenesulfonate) (TsO-PEG3-OTs) to obtain the precursor (LXH-254-OTs) and a nucleophilic substitution reaction with 18F to obtain the tracer ([18F]F-LXH-254). [18F]F-LXH-254 exhibited good molar activity (7.16 ± 0.81 GBq/µmol), radiochemical purity (>95%), and stability. Micro-PET imaging revealed distinct radioactivity accumulation of [18F]F-LXH-254 in tumors in the imaging groups, whereas in the blocked group, the tumor radioactivity level was consistent with the background tissue, illustrating the affinity and specificity of [18F]F-LXH-254 in targeting RAF. Overall, [18F]F-LXH-254 is a promising radiotracer for screening and diagnosing patients with RAF-related disease and monitoring their treatment. This is the first attempt at using an 18F-labeled RAF-specific radiotracer.

MA'AT analysis of the O-glycosidic linkages of oligosaccharides using nonconventional NMR J-couplings: MA'AT and MD models of phi.

MA'AT analysis (Meredith et al., J. Chem. Inf. Model. 2022, 62, 3135-3141) is a new NMR-based method to treat ensembles of redundant NMR spin-coupling constants (J-couplings) to obtain experiment-based probability distributions of molecular torsion angles in solution. Work reported to date on modeling the conformations of O-glycosidic linkages of oligosaccharides using three conventional J-coupling constraints (2 J COC, 3 J COCH, 3 J COCC) has shown that the method gives mean torsion angles and circular standard deviations (CSDs) for psi in very good agreement with those obtained by MD simulation. On the other hand, CSDs for phi determined by MA'AT analysis have consistently been much larger than those determined by MD, calling into question either the reliability of MA'AT analysis or MD to accurately predict this behavior. Prior work has shown that this discrepancy does not stem from the limitations of DFT-based J-coupling equation parameterization where secondary conformational dependencies can introduce uncertainties. The present work re-visits this problem by incorporating a new nonconventional J-coupling constraint into MA'AT analyses of phi, namely, a geminal (two-bond) 2 J CCH J-value that exhibits a strong primary dependence on phi. The latter property pertains explicitly to linkages contributed by GlcNAc pyranosyl rings and pyranosyl rings devoid of substituents at C2 (i.e., deoxy residues) where known secondary contributions to 2 J CCH magnitude caused by C-O bond rotation involving the coupled carbon are negligible or absent. The results show that when 2 J CCH values are added to the analysis, phi CSDs reduce considerably, bringing them into better alignment with those obtained by MD simulation. The cause of the discrepancy when only three conventional J-couplings are used to treat phi appears to be associated with the two-bond 2 J COC, which has properties that make it less effective than the non-conventional 2 J CCH as a discriminator of different conformational models of phi.

Encapsulated lactiplantibacillus plantarum improves Alzheimer's symptoms in APP/PS1 mice.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder that can result in neurotoxicity and an imbalance in gut microbiota. Probiotics have been shown to play an important role in regulating the gut microbiota, but their viability and bioactivity are often compromised as they traverse the gastrointestinal tract, thereby reducing their efficacy and limiting their clinical utility. RESULTS: In this work, layer-by-layer (LbL) encapsulation technology was used to encapsulate Lactiplantibacillus plantarum (LP) to improve the above shortcomings. Studies in APPswe/PS1dE9 (APP/PS1) transgenic mice show that LbL-encapsulated LP ((CS/SP)2-LP) protects LP from gastrointestinal damage while (CS/SP)2-LP treatment It improves brain neuroinflammation and neuronal damage in AD mice, reduces Aß deposition, improves tau protein phosphorylation levels, and restores intestinal barrier damage in AD mice. In addition, post-synaptic density protein 95 (PSD-95) expression increased in AD mice after treatment, indicating enhanced synaptic plasticity. Fecal metabolomic and microbiological analyzes showed that the disordered intestinal microbiota composition of AD mice was restored and short-chain fatty acids (SCFAs) levels were significantly increased after (CS/SP)2-LP treatment. CONCLUSION: Overall, the above evidence suggests that (CS/SP)2-LP can improve AD symptoms by restoring the balance of intestinal microbiota, and (CS/SP)2-LP treatment will provide a new method to improve the symptoms of AD patients.

Photoinduced Radical Annulations of Tetrahydroisoquinoline Derivatives with 2-Benzothiazolimines: Highly Diastereoselective Synthesis of Fused Hexahydroimidazo[2,1-a]isoquinolines.

We report herein a photoinduced radical 1,3-dipolar cycloaddition between the 2-benzothiazolimines and tetrahydroisoquinoline derivatives with an organo-photocatalyst. A variety of benzothiazole-based hexahydroimidazo[2,1-a]isoquinoline architectures with great synthetic value were conveniently and efficiently constructed in moderate to good yields and excellent diastereoselectivities with highly tolerant functional groups. Moreover, the practicality and utility of this protocol were demonstrated by scale-up synthesis and facile elaboration. Preliminary mechanistic investigations indicated that the reaction proceeded via a visible-light-induced radical 1,3-dipolar cycloaddition pathway. This finding is expected to stimulate a more extensive exploration of the green and concise synthesis of structurally diverse heterocyclic molecules in the synthetic community.

[Comparison and application of obesity screening indicators in children and adolescents aged 6-18 years in Hangzhou in 2023].

OBJECTIVE: To determine the percentile reference values and reference curves of total body fat percentage in children and adolescents by sex and age, and to evaluate the reliability of different anthropometric indicators in screening for obesity in children and adolescents in order to explore the validity and practicality of a large-scale screening tool for childhood obesity and its desirable thresholds. METHODS: A total of 5983 children and adolescents aged 6-18 years from six primary and secondary schools were selected by stratified randomised cluster sampling in Hangzhou City in 2023, and their weight, height, waist and hip circumferences were measured, and the children's total body fat content was measured using the bioelectrical resistance-antibody composition analyser. A generalised additive model(GAMLSS) was used to construct a percentile reference curve for children's body fat percentage, and the performance of each anthropometric measure in correctly classifying children and adolescents as obese was assessed using receiver operating characteristic(ROC) curves. RESULTS: Over the period 6-18 years, body fat percentage in girls tended to increase with age from year to year, whereas in boys it tended to increase and then decrease. Fat mass index was the main factor contributing to the difference in BMI at the same age and sex(the optimal cutoff values were 26.82 and 24.52, with AUC values of 0.988 and 0.992, respectively), and the contribution of fat mass index was greater in those with a higher BMI. BMI, which had the largest area under the curve for both boys and girls, was the best indicator for assessing obesity in children and adolescents; the waist-to-height ratio(WHtR), with small variability and equally large area under curve values(0.980 for boys and 0.970 for girls), could simultaneously meet the requirements of accuracy and practicality for obesity assessment in mass screening of children and adolescents. CONCLUSION: This study establish the percentile reference value and reference curve of body fat percentage of children and adolescents aged 6-18 years in Hangzhou based on bioelectrical impedance method, and found that WHtR is a simple, effective and practical screening tool for childhood obesity with low variability, which can provide a reference basis for evaluating growth and development and identifying obesity in children aged 6-18 years in this region.

Capture of Iodine in Vapor and Solution Phases by a Th-Based Metal-Organic Framework.

The efficient capture of radioactive iodine is of paramount importance due to its harmfulness. In this work, a new Th-based metal-organic framework (ECUT-Th-11) for iodine capture was reported. ECUT-Th-11 exhibited a relatively high capacity of capturing vapor iodine (2.03 g/g). Besides, the maximal adsorption capacity of iodine in a cyclohexane solution reaches 258.03 mg/g. All of the results demonstrated that ECUT-Th-11 could be a candidate material for the effective removal of waste iodine.

Diagnostic Value of SAA Levels and Perianal Symptoms in the Complicated Perianal Abscesses Among Mpox-Infected Patients.

Objective: Precise prediction of the occurrence of complicated perianal abscesses (PAs) in monkeypox (mpox)-infected patients is important for therapeutic optimization. This study sought to identify risk factors of complicated PA. Methods: A total of 48 patients with mpox infection (PA group, n = 10; non-PA (NPA) group, n = 38) were enrolled in our study, who were hospitalized in Hangzhou Xixi Hospital, China from 29 June to 3 September 2023. The data of demographic characteristics, and clinical symptoms, serum SAA, PCT, CRP, and IL-6 levels were collected by the Electronic Medical Record. The diagnostic values of these biomarkers were assessed using multivariate logistic regression and ROC curve analyses. Results: A decrease in serum IL-6, SAA, and CRP levels (all p-value < 0.05), but not PCT, was observed in all mpox-infected patients. A significant positive correlation was also noted between IL-6, SAA, CRP, and PCT levels (all p-value < 0.05). There was a significant increase in IL-6 and SAA levels and the SAA/CRP ratio in serum samples from patients in the PA group. Multivariate logistic regression and ROC curve analyses identified that the combined use of perianal symptoms and SAA was more sensitive than perianal symptoms or SAA alone as predictors of complicated PA. This combination had the highest predictive value for disease progression, with an AUC of 0.920 (p-value < 0.001). Conclusion: The combination of perianal symptoms and SAA levels was strongly linked to the occurrence of complicated PA in mpox-infected patients. These findings may inform the early diagnosis of this patient population.

Toward establishing a rapid constant temperature detection method for canine parvovirus based on endonuclease activities.

Canine parvovirus (CPV) can cause high morbidity and mortality rates in puppies, posing a significant threat to both pet dogs and the breeding industry. Rapid, accurate, and convenient detection methods are important for the early intervention and treatment of canine parvovirus. In this study, we propose a visual CPV detection system called nucleic acid mismatch enzyme digestion (NMED). This system combines loop-mediated isothermal amplification (LAMP), endonuclease for gene mismatch detection, and colloidal gold lateral chromatography. We demonstrated that NMED can induce the binding of the amplicon from the sample to the specific labeling probe, which in turn triggers digestion by the endonuclease. The sensitivity and visual visibility of LAMP were increased by combining endonuclease and colloidal gold lateral chromatography assisted by a simple temperature-controlled device. The sensitivity of the NMED assay was 1 copy/µL, which was consistent with quantitative PCR (qPCR). The method was validated with 20 clinical samples that potentially had CPV infection; 15 positive samples and 5 negative samples were evaluated; and the detection accuracy was consistent with that of qPCR. As a rapid, accurate, and convenient molecular diagnostic method, NMED has great potential for application in the field of pathogenic microorganism detection. IMPORTANCE: The NMED method has been established in the laboratory and used for CPV detection. The method has several advantages, including simple sampling, high sensitivity, intuitive results, and no requirement for expensive equipment. The establishment of this method has commercial potential and offers a novel approach and concept for the future development of clinical detection of pathogenic microorganisms.

Pancreatic agenesis and altered m6A methylation in the pancreas of PDX1-mutant cynomolgus macaques.

As an essential transcriptional activator, PDX1 plays a crucial role in pancreatic development and ß-cell function. Mutations in the PDX1 gene may lead to type 4 maturity-onset diabetes of the young (MODY4) and neonatal diabetes mellitus. However, the precise mechanisms underlying MODY4 remain elusive due to the paucity of clinical samples and pronounced differences in pancreatic architecture and genomic composition between humans and existing animal models. In this study, three PDX1-mutant cynomolgus macaques were generated using CRISPR/Cas9 technology, all of which succumbed shortly postpartum, exhibiting pancreatic agenesis. Notably, one tri-allelic PDX1-mutant cynomolgus macaque (designated as M4) developed a pancreas, whereas the two mono-allelic PDX1-mutant cynomolgus macaques displayed no anatomical evidence of pancreatic formation. RNA sequencing of the M4 pancreas revealed substantial molecular changes in both endocrine and exocrine functions, indicating developmental delay and PDX1 haploinsufficiency. A marked change in m6A methylation was identified in the M4 pancreas, confirmed through cultured PDX1-mutant islet organoids. Notably, overexpression of the m6A modulator METTL3 restored function in heterozygous PDX1-mutant islet organoids. This study highlights a novel role of m6A methylation modification in the progression of MODY4 and provides valuable molecular insights for preclinical research.

Impact of the nail insertion angle on the wedge effect in intramedullary nail fixation of intertrochanteric hip fractures.

BACKGROUND: The wedge effect is known to be influenced by the insertion of the proximal femoral intramedullary nail through the fracture line and the large proximal diameter of the nail. However, the impact of the nail insertion angle (NIA) on the wedge effect remains unclear. This study aimed to investigate: (1) how to evaluate the NIA intraoperatively, (2) whether the NIA is associated with the wedge effect, (3) whether the NIA can serve as a reliable predictor of the wedge effect, (4) which factors affect the NIA, and (5) which surgical techniques can prevent the occurrence of the wedge effect associated with the NIA. HYPOTHESIS: We hypothesized that an excessive NIA is related to the wedge effect and that lateral deviation of the entry point is associated with an excessive NIA. PATIENTS AND METHODS: Intraoperative fluoroscopy images of patients who underwent intramedullary nail fixation for intertrochanteric hip fractures between 2013 and 2023 were analyzed. NIA and insertion point distance (IPD) were measured on hip anteroposterior radiographs with the guidewire inserted. Femoral shaft lateralization (FSL) and neck-shaft angle (NSA) were measured on hip anteroposterior radiographs before and after nail insertion; differences in FSL and NSA were calculated. A negative difference in FSL combined with a positive difference in NSA indicated the occurrence of the wedge effect. Pearson's correlation test was used to determine relationships between continuous variables (NIA, FSL, NSA, and IPD). Binary logistic regression analyzed the association between NIA and the wedge effect. Receiver operating characteristic (ROC) curve analysis was used to determine the threshold value of NIA, with predictive performance assessed using the area under the ROC curve (AUC). Other potential factors influencing the wedge effect were also examined. RESULTS: A total of 408 patients were included. The mean NIA was 15.61 ± 4.49 °. Post-nail insertion, the average increase in FSL was 3.20 mm, and the average decrease in NSA was 1.90 °. Pearson's correlation test revealed that NIA was negatively correlated with the difference in FSL (R = 0.565, P < 0.001) and positively correlated with the difference in NSA (R = 0.509, P < 0.001). Binary logistic regression showed a significant correlation between NIA and the wedge effect (P < 0.001). ROC analysis indicated that the AUC for NIA was 0.813, with an optimal cutoff point of 14.85 °. IPD was positively correlated with NIA (R = 0.519, P < 0.001). Unstable fractures were associated with increased lateralization of the femoral shaft after nail insertion (P = 0.003). DISCUSSION: The NIA is positively correlated with the wedge effect in intramedullary nail fixation of intertrochanteric hip fractures. The wedge effect tends to occur when the NIA is >14.85 °, particularly in unstable fractures. Lateral deviation of the entry point is associated with an excessive NIA. Adducting the affected limb, moving the entry point slightly medial and using a medial pusher may help control the NIA to less than 14.85 ° to reduce the wedge effect. LEVEL OF EVIDENCE: III.

Effects of the teach-back method on the health status of patients with chronic obstructive pulmonary disease: a real-world community-based cluster-randomized controlled trial.

Background: The teach-back method (TBM), also known as the "show-me" method, is a technique for verifying patients' understanding of health-related information that has been recommended for improving health literacy. However, the research on TBM effect on the outcomes of chronic obstructive pulmonary disease (COPD) patients is limited. Therefore, the aim of this study was to examine the effect of a TBM intervention on the health status of COPD patients. Methods: This real-world community-based cluster-randomized controlled trial enrolled 1,688 patients with COPD from 18 communities in China. Participants received either TBM plus usual care (UC) or UC only. General practitioners were trained in TBM before the intervention. The primary outcomes were depression and anxiety symptoms, as measured by the Hospital Anxiety and Depression Scale (HADS). The secondary outcomes were health-related quality of life and dyspnea, as measured by the COPD Assessment Test (CAT). Dyspnea was assessed using the modified Medical Research Council (mMRC) dyspnea scale. Data on acute exacerbations and deaths were extracted from medical records. Lung function was expressed as the forced expiratory volume in 1 second as a percentage of the predicted value [FEV1 (% pred)]. Results: In total, 336 of the 853 COPD patients in the intervention group (TBM plus UC) had comorbid depression, compared with 329 of the 835 in the control group (UC only). The TBM group showed a significantly greater improvement in HADS depression and anxiety subscale scores (HADS-D and HADS-A, respectively) than the UC group at12 months (t =8.34, P<0.001; t=12.18, P<0.001). The CAT and mMRC scores were significantly lower in the TBM than UC group at 12 months (t=8.43, P<0.001; t=7.23, P<0.001). The numbers of acute exacerbations and deaths were significantly lower in the TBM than UC group at 12 months (mean MCF values were 0.35 and 0.56, respectively [difference of 0.22; 95% confidence interval (CI): -0.41, -0.02; χ2=9.63, P<0.001]. The FEV1 (% pred) was significantly higher in the TBM than UC group at 12 months (t=7.45, P<0.001). Conclusions: General practitioners can use TBM interventions to effectively reduce anxiety, depression, and dyspnea symptoms, decrease the frequency of exacerbations and likelihood of death, and improve health-related quality of life and pulmonary function in patients with COPD. Trial Registration: The trial was registered on the Chinese Clinical Trials Registry (reference: ChiCTR-TRC-12001958).

Clinical Value of ABCB1 and PAI-1 Gene Polymorphisms in Predicting Glucocorticoid-induced Adverse Reactions in Nephrotic Syndrome Patients.

OBJECTIVE: Glucocorticoid (GC)-induced adverse reactions (ARs) have been extensively studied due to their potential impact on patients' health. This study aimed to examine the potential correlation between two polymorphisms [adenosine triphosphate-binding cassette B1 (ABCB1) C3435T and plasminogen activator inhibitor-1 (PAI-1) 4G/5G] and various GC-induced ARs in nephrotic syndrome (NS) patients. METHODS: In this study, 513 NS patients who underwent GC treatment were enrolled. Then, the patients were divided into two groups based on ABCB1 C3435T and PAI-1 4G/5G genotyping, and intergroup comparisons of clinicopathological data and GC-induced ARs were performed. Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs, and a nomogram was subsequently established and validated via the area under the ROC curve (AUC), calibration curve and decision curve analysis (DCA). RESULTS: We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head (SANFH) (OR: 2.191, 95% CI: 1.258-3.813, P=0.006) but not as a risk factor for the occurrence of steroid diabetes mellitus (S-DM). On the other hand, PAI-1 4G/5G was identified as an independent risk factor for the development of both SANFH (OR: 2.198, 95% CI: 1.267-3.812, P=0.005) and S-DM (OR: 2.080, 95% CI: 1.166-3.711, P=0.013). Notably, no significant correlation was found between the two gene polymorphisms and other GC-induced ARs. In addition, two nomograms were established and validated to demonstrate strong calibration capability and clinical utility. CONCLUSION: Assessing ABCB1 C3435T and PAI-1 4G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.

Proteomic landscape profiling of primary prostate cancer reveals a 16-protein panel for prognosis prediction.

Prostate cancer (PCa) is the most common malignant tumor in men. Currently, there are few prognosis indicators for predicting PCa outcomes and guiding treatments. Here, we perform comprehensive proteomic profiling of 918 tissue specimens from 306 Chinese patients with PCa using data-independent acquisition mass spectrometry (DIA-MS). We identify over 10,000 proteins and define three molecular subtypes of PCa with significant clinical and proteomic differences. We develop a 16-protein panel that effectively predicts biochemical recurrence (BCR) for patients with PCa, which is validated in six published datasets and one additional 99-biopsy-sample cohort by targeted proteomics. Interestingly, this 16-protein panel effectively predicts BCR across different International Society of Urological Pathology (ISUP) grades and pathological stages and outperforms the D'Amico risk classification system in BCR prediction. Furthermore, double knockout of NUDT5 and SEPTIN8, two components from the 16-protein panel, significantly suppresses the PCa cells to proliferate, invade, and migrate, suggesting the combination of NUDT5 and SEPTIN8 may provide new approaches for PCa treatment.

A prognostic biomarker of disulfidptosis constructed by machine learning framework model as potential reporters of pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAAD), known for its high lethality, has not been thoroughly explored in terms of its mechanisms and patterns of immune infiltration. Disulfidptosis, a newly identified mode of cell death, is likely associated with tumorigenesis and progression but remains poorly understood in PAAD at the genetic and mechanistic levels. METHODS: Sixteen PAAD samples from the GSE154778 scRNA-seq dataset were subjected to single-cell analysis. Disulfidptosis grouping and scores were established across various immune cell populations. Using the TCGA-PAAD database, LASSO regression was employed to construct prognostic markers linked to disulfidptosis. The performance of this model was assessed in both training and independent validation cohorts. Subsequent analyses explored the correlations between disulfidptosis scores, immune infiltration, and drug sensitivity. Cellular experiments further confirmed the significant positive relationship of the gene MET with disulfidptosis and its role in influencing the invasion and metastasis of PAAD. RESULTS: WGCNA identified Disulf-High and Disulf-Low as modules strongly correlated with disulfidptosis. Five prognostically significant genes were selected to construct prognostic models. Survival analysis demonstrated that the disulfidptosis-related biological model successfully achieved prognostic stratification in PAAD patients. Additionally, the disulfidptosis score was significantly correlated with both immune infiltration and drug sensitivity. Knockdown of the MET gene substantially inhibited cell multiplication and cell cycle progression in two PAAD cell lines, effects potentially induced by the activation of the PI3K/AKT signalling pathway in the tumour. CONCLUSION: Key genes associated with disulfidptosis significantly correlate with immune infiltration and the development of PAAD. Biomarkers based on disulfidptosis present potential avenues for novel therapies and clinical treatments in PAAD.

Opioid-Induced Constipation and Associated Symptoms After Orthopedic Trauma.

PURPOSE: Opioid-induced constipation is an adverse effect often experienced among patients taking prescription opioid medication. Despite frequent opioid prescribing after orthopedic injury, there is a dearth of research examining opioid-induced constipation presentations in this population. This analysis examines the frequency of opioid-induced constipation manifestations and association with patient-reported outcomes among participants prescribed opioid medication following orthopedic injury. DESIGN: Secondary analysis of 86 clinical trial participants following orthopedic trauma. METHODS: Participants were assessed 2-weeks postoperatively with the following measures: Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference, PROMIS Physical Function, past 24-hour average pain intensity captured on the numeric pain rating scale, and the Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire. Linear regressions examined the association between PAC-SYM scores and both pain intensity and PROMIS T-scores while accounting for injury severity and opioid medication dosage. RESULTS: Most participants (69%) reported experiencing opioid-induced constipation symptoms and 7% reported moderate to severe symptoms. Compared to those without symptoms, participants reporting opioid-induced constipation symptoms were found to have a 3-point increase in PROMIS Pain Interference (95% Confidence Interval [CI]: 0.28-5.90; p = .032), a 3-point decline in PROMIS Physical Function (95% CI: -6.57 to -0.02; p = .049), and a 1.7-point increase in average pain scores (95% CI: 0.50-3.01; p = .007) at 2-weeks following surgery. CONCLUSIONS: Opioid-induced constipation symptoms are common after orthopedic trauma and linked to increased pain interference and pain intensity as well as reduced physical function. CLINICAL IMPLICATIONS: Nurse-led assessments of opioid-induced constipation can support the timely delivery of interventions to alleviate symptoms and potentially improve patient-reported outcomes after injury.

Diagnostic Value of Serum KL-6 in Interstitial Lung Diseases.

Objective: To explore serum KL-6 level and investigate its diagnostic value in interstitial lung diseases (ILDs). Methods: Serum KL-6 level was measured using the chemiluminescent enzyme immunoassay. Statistical analysis was performed for determining the KL-6 concentration of each group. Results: KL-6 level (U/mL) in the ILD group was 1388.321 ±1943.116, which was higher than that in the control group, showing a significant statistical difference. ROC curve analysis based on the receiver operating characteristic curve showed the optimal cut-off value of 402.5U/mL, sensitivity of 77.4%, specificity of 93.4%, and accuracy of 89.4%; through Chi-square test with the two groups, the positive rate of KL-6 in patients with ILD was proved to be significantly higher than that in the control group. KL-6 level was 1063.00±504.757 in the idiopathic pulmonary fibrosis (IPF) group, 1346.892 ±1827.252 in the connective tissue disease-associated interstitial lung disease (CTD-ILD) group, 467.889±288.859 in the organizing pneumonia (OP) group, 8252.333±6050.625 in the pulmonary alveolar proteinosis (PAP) group, and 359.200±392.707 in the sarcoidosis group. The rank sum test showed that the differences were statistically significant. KL-6 level was the lowest in the sarcoidosis group, followed by that in the OP group. Conclusion: Serum KL-6 level was confirmed to be highly sensitive, specific, and accurate in the diagnosis of ILD. Subgroup analysis showed that the KL-6 level was the lowest in the sarcoidosis group, followed by that in the OP group.

Step feature line extraction from large-scale point clouds of open-pit mine based on structural characteristics.

High-precision step feature lines play a crucial role in open-pit mine design, production scheduling, mining volume calculations, road network planning, and slope maintenance. Compared with the feature lines of the geometric model, step feature lines are more irregular, complex, higher in density, and richer in detail. In this study, a novel technique for extracting step feature line from large-scale point clouds of open-pit mine by leveraging structural attributes, that is, SFLE_OPM (Step Feature Line Extraction for Open-Pit Mine), is proposed. First, we adopt the k-dimensional tree (KD-tree) resampling method to reduce the point-cloud density while retaining point-cloud features and utilize bilateral filtering for denoising. Second, we use Point Cloud Properties Network (PCPNET) to estimate the normal, calculate the slope and aspect, and then filter them. We then apply morphological operations to the step surface and obtain more continuous and smoother slope lines. In addition, we construct an Open-Pit Mine Step Feature Line (OPMSFL) dataset and benchmarked SFLE_OPM, achieving an accuracy score of 89.31% and true positive rate score of 80.18%. The results demonstrate that our method yields a higher extraction accuracy and precision than most of the existing methods. Our dataset is available at https://github.com/OPMDataSets/OPMSFL .

Influenza A virus infection activates caspase-8 to enhance innate antiviral immunity by cleaving CYLD and blocking TAK1 and RIG-I deubiquitination.

Caspase-8, an aspartate-specific cysteine protease that primarily functions as an initiator caspase to induce apoptosis, can downregulate innate immunity in part by cleaving RIPK1 and IRF3. However, patients with caspase-8 mutations or deficiency develop immunodeficiency and are prone to viral infections. The molecular mechanism underlying this controversy remains unknown. Whether caspase-8 enhances or suppresses antiviral responses against influenza A virus (IAV) infection remains to be determined. Here, we report that caspase-8 is readily activated in A549 and NL20 cells infected with the H5N1, H5N6, and H1N1 subtypes of IAV. Surprisingly, caspase-8 deficiency and two caspase-8 inhibitors, Z-VAD and Z-IETD, do not enhance but rather downregulate antiviral innate immunity, as evidenced by decreased TBK1, IRF3, IκBα, and p65 phosphorylation, decreased IL-6, IFN-ß, MX1, and ISG15 gene expression; and decreased IFN-ß production but increased virus replication. Mechanistically, caspase-8 cleaves and inactivates CYLD, a tumor suppressor that functions as a deubiquitinase. Caspase-8 inhibition suppresses CYLD cleavage, RIG-I and TAK1 ubiquitination, and innate immune signaling. In contrast, CYLD deficiency enhances IAV-induced RIG-I and TAK1 ubiquitination and innate antiviral immunity. Neither caspase-3 deficiency nor treatment with its inhibitor Z-DEVD affects CYLD cleavage or antiviral innate immunity. Our study provides evidence that caspase-8 activation in two human airway epithelial cell lines does not silence but rather enhances innate immunity by inactivating CYLD.

Yu-Shiba-Rusinov States in s-Wave Kagome Superconductors: Self-Consistent Bogoliubov-de Gennes Calculations.

Significant research has recently been conducted into the Yu-Shiba-Rusinov (YSR) states in kagome superconductors through theoretical modeling and experimental investigations. However, additional efforts are still needed to further understand the local superconductivity near magnetic impurities in the kagome lattice and clarify how relevant quantities depend on the interaction strength, J, between such impurities and electrons. In this study, we explore a self-consistent numerical solution of the Bogoliubov-de Gennes equations for an s-wave superconducting Kagome model with a single classical magnetic impurity. Our study reveals that with increasing J, the local pair potential is systematically depressed in the vicinity of the impurity, similar to previous results obtained for the square and triangular lattices. Moreover, when J is further increased, the system undergoes a first-order phase transition with the appearance of stable and metastable states, reflecting the presence of the hysteresis loop in the pertinent quantities. As a consequence of this transition, the minimal energy of the stable YSR state is nonzero at any J, contrary to the expectations based on the assumption of a constant pair potential. A distinctive feature of the kagome lattice is that characteristics of the first-order transition are very sensitive to the position of the chemical potential within the kagome energy spectrum.