Search

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Mobile Edge Computing (MEC)-based computation offloading is a promising application paradigm for serving large numbers of users with various delay and energy requirements. In this paper, we propose a flexible MEC-based requirement-adaptive partial offloading model to accommodate each user's specific preference regarding delay and energy consumption. To address the dimensional differences between time and energy, we introduce two normalized parameters and then derive the computational overhead of processing tasks. Different from existing works, this paper considers practical variations in the user request patterns, and exploits a flexible partial offloading mode to minimize computation overheads subject to tolerable delay, task workload and power constraints. Since the resulting problem is non-convex, we decouple it into two convex subproblems and present an iterative algorithm to obtain a feasible offloading solution. Numerical experiments show that our proposed scheme achieves a significant improvement in computation overheads compared with existing schemes.

Abstract The coronavirus disease 2019 (COVID‐19) has developed into a global health crisis. Pulmonary fibrosis, as one of the complications of SARS‐CoV‐2 infection, deserves attention. As COVID‐19 is a new clinical entity that is constantly evolving, and many aspects of disease are remain unknown. The datasets of COVID‐19 and idiopathic pulmonary fibrosis were obtained from the Gene Expression Omnibus. The hub genes were screened out using the Random Forest (RF) algorithm depending on the severity of patients with COVID‐19. A risk prediction model was developed to assess the prognosis of patients infected with SARS‐CoV‐2, which was evaluated by another dataset. Six genes (named NELL2, GPR183, S100A8, ALPL, CD177, and IL1R2) may be associated with the development of PF in patients with severe SARS‐CoV‐2 infection. S100A8 is thought to be an important target gene that is closely associated with COVID‐19 and pulmonary fibrosis. Construction of a neural network model was successfully predicted the prognosis of patients with COVID‐19. With the increasing availability of COVID‐19 datasets, bioinformatic methods can provide possible predictive targets for the diagnosis, treatment, and prognosis of the disease and show intervention directions for the development of clinical drugs and vaccines.

AIM: To study retinal microvascular and microstructural alterations in meibomian gland dysfunction (MGD) in severely obese population using optical coherence tomography angiography (OCTA). METHODS: Twelve MGD patients with severely obese population (PAT group; 24 eyes) and 12 healthy controls (HC group; 24 eyes) were recruited. OCTA images were segmented into five [superior (S), nasal (N), inferior (I), temporal (T), and central foveal (C)] or nine [inner superior (IS), outer superior (OS), inner nasal (IN), outer nasal (ON), inner inferior (II), outer inferior (OI), inner temporal (IT), outer temporal (OT), and C] subregions. The superficial vessel density (SVD), retinal thickness (RT), foveal avascular zone (FAZ) parameters, and retinal volume were measured. RESULTS: Visual acuity was significantly different between two groups (0.8±0.17 in PAT group vs 0.2±0.06 in HC group). SVD was significantly lower in PATs in N, T, OS, IN, OT, and ON. The area under the receiver operating characteristic curve (AUC) for T was 0.961 [95% confidence interval (CI): 0.908 to 1.000], for OS was 0.962 (95%CI: 0.915 to 1.000). RT was significantly lower in PATs in IS, OS, OI, OT, ON, IT, IN, and II. AUC for OT was 0.935 (95%CI: 0.870 to 0.999), for IS was 0.915 (95% CI: 0.838 to 0.992). Angiography results showed significantly lower area and perimeter of FAZ, SVD of the inner retina and both retinal volume and the average volume thickness in the PAT group. CONCLUSION: Vision may be affected in patients with MGD due to changes in retinal microvessels and microstructures. These changes detected by OCTA may be a potential marker for diagnosing MGD in severe obesity.

Objective To study the buccolingual inclination of posterior premolars and molars and the curve of Wilson in patients with different sagittal skeletal patterns, to explore the compensation mechanism of horizontal inclination of posterior teeth in patients with different sagittal skeletal patterns and to provide a reference for the control of posterior tooth inclination in the treatment of bone malocclusion. Methods This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Ninety CBCT scans of adults and ninety scans of adolescents before orthodontic treatment were evaluated in this cross-sectional study. There were 30 skeletal Class I, Class Ⅱ, and Class Ⅲ patients in the adult group and adolescent group. The inclination angles of posterior teeth and the curve of Wilson of first and second molars were measured, and data were analyzed between adolescents and adults with different sagittal skeletal patterns. Results Compared with skeletal Class Ⅰ adult patients, the upper posterior molar inclination of skeletal Class Ⅱ patients was significantly lower, and the lower posterior molar inclination was significantly higher. Compared with skeletal ClassⅠ adult patients, the upper posterior molar inclination of skeletal Class Ⅲ adult patients was higher, and the lower posterior molar inclination was significantly lower. The Wilson curve of the second molar in skeletal Class Ⅱ adult patients was significantly higher than that in the other groups. Compared with skeletal ClassⅠ adolescent patients, skeletal Class Ⅲ adolescent patients had a significantly higher upper posterior molar inclination; however, no difference was found between the inclination of the posterior teeth between skeletal Class Ⅰ, Class Ⅱ and Class Ⅲ adolescent patients. Comparing adolescent and adult samples, in skeletal Class Ⅱ patients, adults showed more lingual inclination than adolescents in the upper posterior teeth and less lingual inclination in the lower posterior teeth except for the mandibular first molar. Comparing adolescent and adult samples, in skeletal Class Ⅲ patients, adults showed more lingual inclination than adolescents in the lower posterior teeth except for the mandibular second molars and showed no difference in the upper posterior teeth. Conclusions The inclination of the posterior teeth and the curve of Wilson show significant differences between the three sagittal skeletal patterns. Compared with those of skeletal Class Ⅰ patients, the posterior teeth of skeletal Class Ⅱ patients show more lingual inclination in the upper arch and less lingual inclination in the lower arch. Meanwhile, posterior teeth of skeletal Class Ⅲ patients show more lingual inclination in the lower arch and maintain the inclination in the upper arch.

Abstract Background The addition of coronary artery calcium score (CACS) to prediction models has been verified to improve performance. Machine learning (ML) algorithms become important medical tools in an era of precision medicine, However, combined utility by CACS and ML algorithms in hypertensive patients to forecast obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CCTA) is rare. Methods This retrospective study was composed of 1,273 individuals with hypertension and without a history of CAD, who underwent dual-source computed tomography evaluation. We applied five ML algorithms, coupled with clinical factors, imaging parameters, and CACS to construct predictive models. Moreover, 80% individuals were randomly taken as a training set on which 5-fold cross-validation was done and the remaining 20% were regarded as a validation set. Results 16.7% (212 out of 1,273) of hypertensive patients had obstructive CAD. Extreme Gradient Boosting (XGBoost) posted the biggest area under the receiver operator characteristic curve (AUC) of 0.83 in five ML algorithms. Continuous net reclassification improvement (NRI) was 0.55 (95% CI (0.39–0.71), p

Abstract Objective To describe a novel method of medial fixation of titanium mesh with a right‐angled screwdriver for orbital floor and maxillary reconstruction and to compare the reconstruction outcome of orbital floor reconstruction with modified and traditional methods. Methods The data of 23 patients who underwent maxillectomy and orbital floor defect reconstruction by individualized titanium mesh in Peking University School and Hospital of Stomatology between 2018 and 2021 were retrospectively reviewed. While eight patients received modified orbital floor reconstruction with titanium mesh and angled screwdriver (group A), 15 patients received traditional orbital floor reconstruction (group B). The contact area with buccal flap for titanium mesh in groups A and B was calculated. Titanium mesh deformation, fracture or exposure was recorded. Postoperative ophthalmic function and success of esthetic restoration were assessed. Results Mean follow‐up was for 15.7 months (range, 9–22 months). The contact area with buccal flap for the modified titanium mesh in group A (13.11 ± 1.41 cm2) was significantly less than that of the traditional titanium mesh in group B (21.83 ± 1.23 cm2; p .05). No specific complications were reported. Conclusion We propose a novel method of zygomatic medial fixation of titanium mesh with a right‐angled screwdriver for orbital floor and maxillary reconstruction, which has the potential to prevent the postoperative exposure of titanium mesh. Level of Evidence Level III (Retrospective comparative study).

Reef islands are composed of unconsolidated carbonate sediment from the reef that has been organized and deposited on an atoll and platform reef by ocean hydrodynamics. They are frequently found in remote mid-ocean locations within tropical and subtropical waters and are the sole source for habitable land of some island nations. It is anticipated that sea level rise and more frequent and intense storms resulting from global climate change will destabilize these low-lying reef islands, thus there is increasing concern about the persistence and habitability of these islands during future extreme wave events. The reef island morphodynamic response to the action of regular waves has not been reported in the literature. Therefore, this study performed laboratory experiments based on a horizontally one-dimensional reef island physical model in a wave flume. The temporal variation of the island profile under regular waves was measured to analyze the effects of island morphological factors (initial island height and width) and initial island location on its topographic evolution. The results showed that the reef island lost crest elevation and migrated and extended toward its lagoon side under the action of regular waves. Accretion also occurred on the lagoon side beach and random ripples appeared. The time required for the island to reach its equilibrium profile decreased with increasing of initial island height, initial island width, and initial island distance from reef edge. The island crest lowering due to scouring increased with increase of initial island height, but it decreased with increasing of initial island width and initial island distance from the reef edge. Among the three factors, initial island height had the greatest impact on the crest lowering. The island lagoonward migration decreased with increasing of both initial island height and initial island distance from reef edge, but it increased with the increase of initial island width. Among the three factors, initial island location was the most influential factor to lagoonward migration, but no island lagoonward migration was detected when the initial island distance D≥2 m. Regression analysis was used to obtain empirical formulae to predict the island crest lowering and island lagoonward migration, respectively. The outcomes of this study provide a habitability assessment for such low-lying island nations in the context of global climate change.

Abstract Cartilage oligomeric matrix protein (COMP) interacts with various extracellular matrix proteins in tissues. Elevated COMP levels recently linked to worse overall survival in multiple cancer types. COMP's significance in intrahepatic cholangiocarcinoma (iCCA) remains uncertain. Here we report a retrospective study to explore COMP's impact on iCCA outcomes. We collected 182 patients' iCCA tumor tissues. COMP overexpression was associated with adverse factors like R1 resection (p = 0.008), advanced T stage (p

Prostate cancer (PCa) is initially sensitive to androgen deprivation therapy (ADT) but ultimately develops resistance and progresses to castration-resistant prostate cancer (CRPC) with a poor prognosis. This study indicated that some PCa patients and mice were more sensitive to ADT and entered CRPC later, which was related to the gut microbiota, especially the enrichment of Akkermansia muciniphila (AKK). Untargeted metabolomics analysis found that serum inosine level was upregulated in the treatment-sensitive group and significantly correlated with AKK. Furthermore, we revealed that intestinal permeability and serum lipopolysaccharide (LPS) levels increased in treatment-resistant mice. LPS stimulated the upregulation of p-NF-κB p65 and AR in tumors. Supplementing AKK metabolite inosine could alleviate intestinal barrier damage and reduce serum LPS level, ultimately inhibiting castration resistance via the LPS/NF-κB/AR axis. Finally, we constructed a predictive model for CRPC combining gut microbiota and clinical information (AUC = 0.729). This study revealed the potential mechanism of gut microbiota on CRPC and provided potential therapeutic targets and prognostic indicators.

This research compared how different levels of dietary crude protein (CP) and apparent metabolizable energy (AME) affect the growth performance, nitrogen utilization, serum parameters, protein synthesis, and amino acid (AA) metabolism in broilers aged 1 to 10 days. In a 4 × 3 factorial experimental design, the broilers were fed four levels of dietary CP (20%, 21%, 22%, and 23%) and three levels of dietary AME (2800 kcal/kg, 2900 kcal/kg, and 3000 kcal/kg). A total of 936 one-day-old male Arbor Acres broilers were randomly allocated to 12 treatments with 6 replications each. Growth performance, nitrogen utilization, serum parameter, gene expression of protein synthesis, and AA metabolism were evaluated at 10 d. The results revealed no interaction between dietary CP and AME levels on growth performance (p > 0.05). However, 22% and 23% CP enhanced body weight gain (BWG), the feed conversion ratio (FCR), total CP intake, and body protein deposition but had a detrimental effect on the protein efficiency ratio (PER) compared to 20% or 21% CP (p < 0.05). Broilers fed diets with 2800 kcal/kg AME showed increased feed intake (FI) and inferior PER (p < 0.05). Broilers fed diets with 3000 kcal/kg AME showed decreased muscle mRNA expression of mammalian target of the rapamycin (mTOR) and Atrogin-1 compared to those fed diets with 2800 kcal/kg and 2900 kcal/kg AME (p < 0.05). Increasing dietary CP level from 20% to 23% decreased muscle mTOR and increased S6K1 mRNA expression, respectively (p < 0.05). The muscle mRNA expression of Atrogin-1 was highest for broilers fed 23% CP diets (p < 0.05). The mRNA expression of betaine homocysteine methyltransferase (BHMT) and Liver alanine aminotransferase of the 22% and 23% CP groups were higher than those of 20% CP (p < 0.05). Significant interactions between dietary CP and AME levels were observed for muscle AMPK and liver lysine-ketoglutarate reductase (LKR) and branched-chain alpha-keto acid dehydrogenase (BCKDH) mRNA expression (p < 0.05). Dietary AME level had no effect on muscle AMPK mRNA expression for broilers fed 21% and 22% CP diets (p > 0.05), whereas increasing dietary AME levels decreased AMPK mRNA expression for broilers fed 23% CP diets (p < 0.05). The mRNA expression of LKR and BCKDH was highest for broilers fed the diet with 2800 kcal/kg AME and 22% CP, while it was lowest for broilers fed the diet with 3000 kcal/kg AME and 20% CP. The findings suggest that inadequate energy density hindered AA utilization for protein synthesis, leading to increased AA catabolism for broilers aged 1 to 10 days, and a dietary CP level of 22% and an AME level of 2900 to 3000 kcal/kg may be recommended based on performance and dietary protein utilization.