Search

Abstract Recent breakthroughs in cancer immunotherapies have emphasized the importance of harnessing the immune system for treating cancer. Vaccines, which have traditionally been used to promote protective immunity against pathogens, are now being explored as a method to target cancer neoantigens. Over the past few years, extensive preclinical research and more than a hundred clinical trials have been dedicated to investigating various approaches to neoantigen discovery and vaccine formulations, encouraging development of personalized medicine. Nucleic acids (DNA and mRNA) have become particularly promising platform for the development of these cancer immunotherapies. This shift towards nucleic acid-based personalized vaccines has been facilitated by advancements in molecular techniques for identifying neoantigens, antigen prediction methodologies, and the development of new vaccine platforms. Generating these personalized vaccines involves a comprehensive pipeline that includes sequencing of patient tumor samples, data analysis for antigen prediction, and tailored vaccine manufacturing. In this review, we will discuss the various shared and personalized antigens used for cancer vaccine development and introduce strategies for identifying neoantigens through the characterization of gene mutation, transcription, translation and post translational modifications associated with oncogenesis. In addition, we will focus on the most up-to-date nucleic acid vaccine platforms, discuss the limitations of cancer vaccines as well as provide potential solutions, and raise key clinical and technical considerations in vaccine development.

BackgroundFor cesarean delivery (CD), the 90% effective dosage (ED90) of oxytocin for a first bolus has been established. It is not yet known how much oxytocin to inject into obese women undergoing elective discectomy to keep their uterine tone (UT) appropriate. We hypothesized that patients who are overweight need a greater dose of oxytocin infusion; thus, we aimed to determine how the dose-response curve for oxytocin infusion changes following an initial 1 international unit (IU) bolus in obese women undergoing elective CD.MethodsOne hundred parturients with a body mass index (BMI) greater than 30 kg/m2 were randomly assigned to receive an infusion rate of 14, 18, 22, or 26 IU/h of oxytocin. When the uterine palpation is as hard as touching the forehead or tip of the nose, it is considered sufficient UT according to the criteria used by obstetricians. The median effective dose (ED50) and ED90 values were determined using probit analysis.ResultsWe found the ED50 and ED90 values for the infusion dose of oxytocin were around 11.0 IU/h and 19.1 IU/h, respectively. Each group had a different number of parturients who needed rescued oxytocin: 14 IU/h for six, 18 IU/h for three, one for 22 IU/h, and none for 26 IU/h. The correlation between the frequency of rescued oxytocin administration and the amount of oxytocin infusion needed to avoid uterine atony was statistically significant (p = 0.02).ConclusionThe present research showed that the most effective dosage of oxytocin infusion for obese parturients undergoing elective CD is 19.1 IU/h, following an initial loading dose of 1 IU. Patients with obesity should receive a greater dosage of prophylactic oxytocin, and further studies comparing patients with and without obesity (with higher BMI) are required.Clinical Trial Registrationhttps://www.chictr.org.cn/showproj.html?proj=159951, identifier ChiCTR2200059582.

Background: Ultrasound (US) can detect salivary gland abnormalities in primary Sjögren's syndrome (SS). This study aimed to compare the correlation among the semiquantitative US scores, texture features, and the quantitative salivary gland scintigraphy (SGS) results. Methods: This retrospective study included 11 patients who were diagnosed with primary SS and underwent US examinations of the parotid glands and SGS simultaneously. We evaluated SGS quantitatively based on the calculation of maximum accumulation ratio (MAR) and stimulated excretion fraction (EF). The US findings were accessed through the semiquantitative Outcome Measures in Rheumatology scoring system and by gray-level co-occurrence matrix (GLCM) texture analysis. Spearman's rank correlation tests were performed. Results: A significant moderate negative correlation was noted between the semiquantitative US score and MAR (rho = −0.57, P = 0.006), but not with EF (rho = −0.11, P = 0.613). The GLCM texture metrics, including contrast, dissimilarity, and homogeneity, were all determined to be significantly associated with both MAR and EF. The GLCM contrast correlated moderately to MAR (rho = −0.66, P = 0.001). The GLCM homogeneity highly correlated to EF (rho = 0.74, P < 0.001). The contrast and homogeneity can still discriminate the changes in MAR and EF in the subgroups with the same semiquantitative US scores. Conclusion: US findings on parotid gland can correlate with SGS results when analyzed based on GLCM texture features. With the GLCM texture metrics, US appears to be an excellent imaging tool for the assessment of the parotid glands in primary SS patients.

Steel-tube-confined concrete (STCC) targets are provided with excellent anti-penetration performance over semi-infinite concrete (SIC) targets since the steel tube imposes passive restraint on the in-filled concrete during the penetration process. Grid STCC system with square steel tubes is a potential solution to protective structures. In this paper, experiments of 9-cell grid STCC targets penetrated by 12.7 mm Armor Piercing Projectile (APP) were performed. The influence of side length and thickness of steel tube, steel ratio and impact velocity on anti-penetration performance were taken into account. Additionally, single-cell square STCC targets were also designed and tested for comparison with the 9-cell grid STCC targets. Damage modes and parameters of the tested targets were measured and discussed. Moreover, the stiffness of radial confinement of grid STCC targets is achieved according to the elastic solution of infinite cylindrical shell in Winkler medium. Furthermore, the penetration resistance and depth of penetration (DOP) for grid STCC targets are obtained on the basis of the dynamic finite spherical cavity-expansion (FSCE) models including radial confinement effect. It is shown that the 9-cell grid STCC targets with optimal dimension match of thickness and side length of steel tube can reduce the DOP by about 17 % and 23 % in comparison with the SIC targets and single-cell square STCC targets, respectively, due to both the confinement of square steel tube to concrete in the impacted cell and the additional confinement of the surrounding cells to the impacted cell; the penetration resistance and DOP of the grid and cellular STCC targets with similar steel ratio is close, and thus the grid STCC targets with simpler manufacturing process and excellent in-plane expandability are preferred in engineering practice; moreover, the predicted results of DOP model based on the FSCE models agree well with the tested results with the maximum disparity less than 12 % and the proposed model is more applicable to the grid and cellular STCC targets with high radial confinement.

ABSTRACT: Objectives: To investigate the clinical outcomes and risk factors of mortality in patients with rheumatic diseases complicated by Pneumocystis pneumonia (PCP). Methods: Between November 2015 and April 2021, patients with rheumatic diseases with PCP in a tertiary referral hospital were retrospectively enrolled. The diagnosis of PCP requires the fulfillment of clinical, radiographic, and microbiological criteria. Factors associated with in-hospital, 30-day, and 90-day mortality were evaluated. Results: A total of 128 patients with rheumatic diseases who had a positive quantitative polymerase chain reaction assay for Pneumocystis jirovecii were screened, and 72 patients were included in the final analysis. The median (interquartile range [IQR]) pneumonia severity index (PSI) was 101.5 (77.0-132.0). The median (IQR) adjunctive corticosteroid dosage was 0.6 (0.4-0.9) mg/kg/day prednisolone equivalent. The receiver operating characteristic curve analysis showed that the optimal cutoff point of median adjunctive corticosteroid dosage was 0.6 mg/kg/day to predict in-hospital, 30-day, and 90-day mortality. In the multivariable logistic regression analysis, median adjunctive corticosteroid dosage ≥0.6 mg/kg/day and PSI >90 were independent factors of in-hospital, 30-day, and 90-day mortality. Conclusion: A median adjunctive corticosteroid dosage of ≥0.6 mg/kg/day might be associated with mortality in patients with rheumatic diseases complicated by PCP.

Upon migrating into the tissues, hematopoietic stem cell (HSC)-derived monocytes differentiate into macrophages, playing a crucial role in determining innate immune responses towards external pathogens and internal stimuli. However, the regulatory mechanisms underlying monocyte-to-macrophage differentiation remain largely unexplored. Here we divulge a previously uncharacterized but essential role for an axon guidance molecule, fibronectin leucine-rich transmembrane protein 2 (FLRT2), in monocyte-to-macrophage maturation. FLRT2 is almost undetectable in human monocytic cell lines, human peripheral blood mononuclear cells (PBMCs), and mouse primary monocytes but significantly increases in fully differentiated macrophages. Myeloid-specific deletion of FLRT2 (Flrt2ΔMyel) contributes to decreased peritoneal monocyte-to-macrophage generation in mice in vivo, accompanied by impaired macrophage functions. Gain- and loss-of-function studies support the promoting effect of FLRT2 on THP-1 cell and human PBMC differentiation into macrophages. Mechanistically, FLRT2 directly interacts with Unc-5 netrin receptor B (UNC5B) via its extracellular domain (ECD) and activates Akt/mTOR signaling. In vivo administration of mTOR agonist MYH1485 reverses the impaired phenotypes observed in Flrt2ΔMyel mice. Together, these results identify FLRT2 as a novel pivotal endogenous regulator of monocyte differentiation into macrophages. Targeting the FLRT2/UNC5B-Akt/mTOR axis may provide potential therapeutic strategies directly relevant to human diseases associated with aberrant monocyte/macrophage differentiation.

Objective: Although the negative impact of immunosuppression on survival in patients with acute respiratory distress syndrome (ARDS) treated by extracorporeal membrane oxygenation (ECMO) is well known, short-term outcomes such as successful weaning rate from ECMO and subgroups benefit most from ECMO remain to be determined. The aims of this study were (1) to identify the association between immunocompromised status and weaning from ECMO in patients of ARDS, and (2) to identify subgroups of immunocompromised patients who may benefit from ECMO.Methods: This retrospective cohort study enrolled patients who received ECMO for ARDS from 2010 to 2020. Immunocompromised status was defined as having a hematological malignancy, active solid tumor, solid organ transplant, or autoimmune disease.Results: This study enrolled 256 ARDS patients who received ECMO, of whom 68 were immunocompromised. The multivariable analysis showed that immunocompromised status was not independently associated with failure to wean from ECMO. In addition, the patients with an autoimmune disease (14/24, 58.3%) and organ transplantation (3/3, 100%) had a numerically higher weaning rate from ECMO than other immunocompromised patients. For causes of ARDS, most patients with pulmonary hemorrhage (6/8, 75%) and aspiration (5/9, 55.6%) could be weaned from ECMO, compared to only a few of the patients with interstitial lung disease (2/9, 22.2%) and sepsis (1/4, 25%).Conclusions: Immunocompromised status was not an independent risk factor of failure to wean from ECMO in patients with ARDS. For patients with pulmonary hemorrhage and aspiration-related ARDS, ECMO may be beneficial as bridge therapy.

In recent years, due to the frequent occurrence of extreme weather due to climate change, the Taiwan region has often suffered from landslides and debris flows in the past 20 years. This study used the ground surface vibration signals collected by the geophone from seven debris flow events in the Shenmu area. Data were processed to represent the time series of velocity and accumulated energy per second. Datasets were established for model training and validation. In this study, Support Vector Machine (SVM) and Random Forest (RF) algorithms were used for comparison. After analyzing the data through balance processing (Synthetic Minority Oversampling Technique, SMOTE), a signal model of debris flow was established. The research results showed that the models using SVM and RF training had good accuracy, recall, and AUC values when choosing input data average of every 6 s and the 10-s time interval within which the data were marked as the occurrence of debris flow. The performance of SVM was better than that of RF after validation. Through the aforementioned research, the vibration signals of debris flow can be regarded as a reference factor, and the model established by the SVM method had acceptable performance and can be used for early-warning of debris flow.

Progressive multifocal leukoencephalopathy (PML) is a rare viral demyelinating disease of central nervous system. Immunosuppression is a significant risk factor for the disease. Previously, PML developed more commonly in patients of hematological malignancy and acquired immune deficiency syndrome (AIDS). In the era of biological disease modifying anti-rheumatic drugs, PML is more frequently reported in patients of autoimmune diseases. However, for its rarity and unspecific clinical presentations, accurate diagnosis and immediate immune restoration might be difficult in clinical practice, and the outcome might thus be miserable. Herein we present a 27-year-old lady of systemic lupus erythematosus (SLE) – rheumatoid arthritis overlap syndrome with suspected involvement of central nervous system. Neuropsychiatric SLE was suspected first. However, after intensive immunosuppressive treatment, the condition kept deteriorating. An alternative diagnosis was thus considered. PML was suspected for her immunosuppressive status and suggestive radiological findings, and the diagnosis was confirmed by a polymerase chain reaction of JC virus from cerebrospinal fluid. After restoring the immune status by decreasing the dose of immunosuppressants, the condition of the patient improved significantly. We report this case to raise the importance of clinical alertness for the rare but possibly underdiagnosed disease. Keywords: Antirheumatic agents, Rheumatoid arthritis, Immunosuppressive agents, Progressive multifocal leukoencephalopathy, Systemic lupus erythematosus

This paper considers a Cournot–Bertrand game model based on the relative profit maximization with bounded rational players. The existence and stability of the Nash equilibrium of the dynamic model are investigated. The influence of product differentiation degree and the adjustment speed on the stability of the dynamic system is discussed. Furthermore, some complex properties and global stability of the dynamic system are explored. The results find that the higher degree of product differentiation enlarges the stable range of the dynamic system, while the higher unit product cost decreases the stable range of price adjustment and increases the one of output adjustment; period cycles and aperiodic oscillation (quasi-period and chaos) occur via period-doubling or Neimark–Sacker bifurcation, and the attraction domain shrinks with the increase of adjustment speed values. By selecting appropriate control parameters, the chaotic system can return to the stable state. The research of this paper is of great significance to the decision-makers’ price decision and quantity decision.

With the unique rainfall patterns of typhoons, plum rains, and short-term heavy rainfalls, the frequent landslide and debris flow disasters have caused severe loss to people in Taiwan. In the studies of landslide susceptibility, the information of factors used for analysis was usually annual-based content, and it was assumed that the same elements from different years were independent between each year. However, the occurrence of landslides was usually not simply due to the changes within a year. Instead, landslides were triggered because the factors that affected the potential of landslides reached critical conditions after a cumulative change with time. Therefore, this study had well evaluated the influence of temporal characteristics and the ratios of antecedent landslide areas in the past five years in the landslide potential evaluation model. The analysis was conducted through the random forest (RF) algorithm. Additional rainfall events of 2017 were used to test the proposed model’s performance to understand its practicality. The analysis results show that in the study area, the RF model had considerably acceptable performance. The results have also demonstrated that the antecedent landslide ratios in the past five years were essential to describe the significance of cumulative change with time when conducting potential landslide evaluation.

A liquid–liquid extraction and ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) method was developed for simultaneous analysis of the residues of seven neonicotinoid insecticides (NEOs), namely acetamiprid, clothianidin, dinotefuran, imidacloprid, thiacloprid, thiamethoxam, and nitenpyram, in commercial milk samples. The method had a good linearity (R2 > 0.992) and a limit of detection range of 0.004–0.15 μg/kg. The average recovery range was 89–119% with an intraday precision of 1.4–10.3% at spiking levels of 8, 12, and 16 μg/kg. The validated method was employed for routine analysis of the aforementioned seven NEOs in commercial milk samples obtained randomly from a supermarket in Miaoli (Taiwan). The detected thiamethoxam and clothianidin levels were 3.4 and 80 μg/kg, respectively.

In this paper, we study a dual-channel closed-loop supply chain in which a manufacturer considers the market waste products recovery and remanufacture, and a retailer considers provide services to customers. We build a Stackelberg game model and a centralized game model in a static and dynamic state, respectively, and analyze the two dynamic models by mathematical analysis and explore the stability and entropy of the two models using bifurcation, the basin of attraction, chaotic attractors, and so on. The influences of service level and profit distribution rate on the system’s profit are discussed. The theoretical results show that higher price adjustment speed will lead to the system lose stability with a larger entropy value. In the Stackelberg game model, the stability of the system increases as the service value and the recovery rate increases; in the centralized model, the stability of the system decreases with the increase of the service value and increases with the recovery rate increases. When the Stackelberg game model is in a stable state, the manufacturer’s profit increases first and then decreases, and the retailer’s profit first decreases and then increases as the service value of the retailer increases. The research will serve as good guidance for both the manufacturer and retailer in dual-channel closed-loop supply chains to improve decision making.

A submicron pixel’s light and dark performance were studied by experiment and simulation. An advanced node technology incorporated with a stacked CMOS image sensor (CIS) is promising in that it may enhance performance. In this work, we demonstrated a low dark current of 3.2 e−/s at 60 °C, an ultra-low read noise of 0.90 e−·rms, a high full well capacity (FWC) of 4100 e−, and blooming of 0.5% in 0.9 μm pixels with a pixel supply voltage of 2.8 V. In addition, the simulation study result of 0.8 μm pixels is discussed.

BACKGROUND: Previous studies observed the high prevalence of venous thromboembolism in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study analyzed the coagulation and fibrinolysis index profile in AAV patients. METHODS: The current study recruited 321 AAV patients in active stage and 78 AAV patients in quiescent stage. Coagulation and fibrinolysis index profiles in these AAV patients were analysed, and their associations with various clinical and pathological parameters were further investigated. RESULTS: The circulating levels of D-dimer, fibrin degradation products and platelet count were significantly higher in AAV patients in active stage compared with those in remission [0.8 (0.4, 1.5) mg/L vs. 0.28 (0.2, 0.55) mg/L, P

Despite the prevalence of multiple choice items in educational testing, there is a dearth of empirical evidence for multiple choice item writing rules. The purpose of this study was to expand the base of empirical evidence by examining the use of the “all-of-the-above” option in a multiple choice examination in order to assess how different student ability groups would respond to this particular alternative. Ten experimentally manipulated items were generated with “all-of-the-above” as one of the options and were incorporated into three different test formats. Test formats were randomly distributed to university students in the study. The test scores in these test formats were compared as well as the experimentally manipulated items. Results showed that when “all-of-the-above” is used as the correct answer, the item is more difficult for all students, despite the literature assumption that it provides a cueing effect to students. Research findings corroborate literature assumptions that high ability students score significantly higher than other ability students in this type of option.

The data of debris-flow events between 2004 and 2001 in the Shebmu area Taiwan were presented and discussed in this paper. Total of 20 debris flows were observed in this time interval. The monitored data include rainfall, flow velocity, soil moisture, and ground surface vibrations. Debris flows in the Shenmu area usually occurred in the Aiyuzi Stream during the rainy season, May to September, and about once per year after 2009. The measured rainfalls from separate monitoring stations were compared and the rainfall thresholds of the Shenmu area were analysed using the rainfall intensity (I), the accumulated rainfall (R), and durations (D). The dataset and the rainfall thresholds of the Shenmu area permits the comparison with other monitored catchments. [ABSTRACT FROM AUTHOR]

In this paper, we give the method to calculate the generalized Gao's constant under the absolute normalized norms in R². Using this method, we can compute the exact values of the generalized Gao's constant of some concrete Banach spaces easily, such as Banach lattice, Lorentz sequence spaces etc. [ABSTRACT FROM AUTHOR]

In this paper, we calculate the precise values of the Heinz means constant under the absolute normalized norms in R² . The conclusions do not only contain some previous results, but also give the exact values of the Heinz means constant for some new concrete Banach spaces. [ABSTRACT FROM AUTHOR]