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Tumour immunotherapy holds great promise as a treatment for cancer, which ranks as the second highest cause of mortality worldwide. This therapeutic approach can be broadly categorized into two main types: active immunotherapy and passive or adoptive immunotherapy. Active immunotherapy, such as cancer vaccines, stimulates the patients’ immune system to target tumour cells. On the other hand, adoptive immunotherapy involves supplying in vitro activated immune cells, such as T cells, natural killer cells and macrophages, to the patient to combat the tumour. Induced pluripotent stem cells are extensively utilized in both active and adoptive tumour immunotherapy due to their pluripotency and ease of gene editing. They can be differentiated into various types of immune cells for direct cancer treatment and can also function as tumour vaccines to elicit an immune response against the tumour. Importantly, iPSCs can be leveraged to develop off-the-shelf allogenic immunotherapy products.
Conclusion
This article provides a comprehensive review of the application of iPSCs in tumor immunotherapy, along with a discussion of the opportunities and challenges in this evolving field.
We in this paper employ a penalized moment selection procedure to identify valid and relevant moments for estimating and testing forecast rationality within the flexible loss framework proposed by Elliott et al. (2005). We motivate the selection of moments in a high-dimensional setting, outlining the fundamental mechanism of the penalized moment selection procedure and demonstrating its implementation in the context of forecast rationality, particularly in the presence of potentially invalid moment conditions. The selection consistency and asymptotic normality are established under conditions specifically tailored to economic forecasting. Through a series of Monte Carlo simulations, we evaluate the finite sample performance of penalized moment estimation in utilizing available instrument information effectively within both estimation and testing procedures. Additionally, we present an empirical analysis using data from the Survey of Professional Forecasters issued by the Federal Reserve Bank of Philadelphia to illustrate the practical utility of the suggested methodology. The results indicate that the proposed post-selection estimator for forecaster’s attitude performs comparably to the oracle estimator by efficiently incorporating available information. The power of rationality and symmetry tests leveraging penalized moment estimation is substantially enhanced by minimizing the impact of uninformative instruments. For practitioners assessing the rationality of externally generated forecasts, such as those in the Greenbook, the proposed penalized moment selection procedure could offer a robust approach to achieve more efficient estimation outcomes.
The heating effect of electromagnetic waves in ion cyclotron range of frequencies (ICRFs) in magnetic confinement fusion device is different in different plasma conditions. In order to evaluate the ICRF heating effect in different plasma conditions, we conducted a series of experiments and corresponding TRANSP simulations on the EAST tokamak. Both simulation and experimental results show that the effect of ICRF heating is poor at low core electron density. The decrease in electron density changes the left-handed electric field near the resonant layer, resulting in a significant decrease in the power absorbed by the hydrogen fundamental resonance. However, quite a few experiments must be performed in plasma conditions with low electron density. It is necessary to study how to make ICRF heating best in low electron density plasma. Through a series of simulation scans of the parallel refractive index (n//) of the ICRF antenna, it is concluded that the change of the ICRF antenna n// will lead to the change of the left-handed electric field, which will change the fundamental absorption of ICRF power by the hydrogen minority ions. Fully considering the coupling of ion cyclotron wave at the tokamak boundary and the absorption in the plasma core, optimizing the ICRF antenna structure and selecting appropriate parameters such as parallel refractive index, minority ion concentration, resonance layer position, plasma current and core electron temperature can ensure better heating effect in the ICRF heating experiments in the future EAST upgrade. These results have important implications for the enhancement of the auxiliary heating effect of EAST and other tokamaks.
The incorporation of trace metals into land snail shells may record the ambient environmental conditions, yet this potential remains largely unexplored. In this study, we analyzed modern snail shells (Cathaica sp.) collected from 16 sites across the Chinese Loess Plateau to investigate their trace metal compositions. Our results show that both the Sr/Ca and Ba/Ca ratios exhibit minimal intra-shell variability and small inter-shell variability at individual sites. A significant positive correlation is observed between the shell Sr/Ca and Ba/Ca ratios across the plateau, with higher values being recorded in the northwestern sites where less monsoonal rainfall is received. We propose that shell Sr/Ca and Ba/Ca ratios, which record the composition of soil solution, may be controlled by the Rayleigh distillation in response to prior calcite precipitation. Higher rainfall amounts may lead to a lower degree of Rayleigh distillation and thus lower shell Sr/Ca and Ba/Ca ratios. This is supported by the distinct negative correlation between summer precipitation and shell Sr/Ca and Ba/Ca ratios, enabling us to reconstruct summer precipitation amounts using the Sr/Ca and Ba/Ca ratios of Cathaica sp. shells. The potential application of these novel proxies may also be promising for other terrestrial mollusks living in the loess deposits globally.
Cardiac complications after haematopoietic cell transplantation in paediatric patients are significant yet under-recognised. Pericardial effusion has been associated with worse outcomes and transplant-related mortality.
Objectives:
We aimed to evaluate the incidence, risk factors, and clinical course of pericardial effusion after paediatric allogeneic haematopoietic cell transplantation. We identified transplantation recipients “at risk” for clinically significant pericardial effusion based on our definition, described our clinical experience and provided recommendations for screening and management.
Study Design:
Clinical data of children who underwent allogeneic haematopoietic cell transplantation at Texas Children’s Hospital from January 2010 to April 2021 were analyzed retrospectively. Factors potentially contributing to time to pericardial effusion, time to pericardial effusion resolution, and overall survival were evaluated.
Results:
We included 629 haematopoietic cell transplantation recipients with a median age at transplantation of 8.5 years (0.1–24.3). Seventy-three patients (11.6%) developed pericardial effusion within a median time of 102 days (1–403) post-haematopoietic cell transplantation, and 50 (68.5%) had resolution of pericardial effusion at the time of last evaluation. Older age at the time of haematopoietic cell transplantation, transplant-associated thrombotic microangiopathy, and cytomegalovirus diagnoses independently increased the risk of pericardial effusion development, while cytomegalovirus diagnosis decreased the likelihood of pericardial effusion resolution. Both non-significant pericardial effusion development and clinically significant effusion development were significantly associated with post-haematopoietic cell transplantation mortality, compared to no pericardial effusion development.
Conclusions:
Paediatric haematopoietic cell transplantation recipients with malignant diseases, older age at the time of transplantation, cytomegalovirus infection, or transplant-associated thrombotic microangiopathy are at higher risk for pericardial effusion development, which in turn predicts worse outcomes with increased risk of death. We propose a model for improved detection, evaluation, and management of pericardial effusion post-haematopoietic cell transplantation.
This study aimed to compare the clinical outcomes of using refrigerated versus pre-warmed media for preparing time-lapse dishes in in vitro fertilization (IVF). Patients undergoing their first IVF/ICSI cycle were divided into two groups. The control group used pre-warmed culture media, while the experimental group used refrigerated culture media. The osmotic pressure of the culture droplets in both groups was tested. No statistical differences were found between the two groups’ basic data. The proportion of air microbubbles affecting imaging significantly decreased (4.55% vs. 37.97%, P < 0.001) when using pre-warmed media. However, the blastocyst formation rate (56.62% vs. 49.70%, P = 0.046) and total high-quality embryo rate (22.26% vs. 17.06%, P = 0.047) were significantly higher in the refrigerated media group compared to the pre-warmed media group. The higher rate of high-quality embryos in the refrigerated media group might result in a higher single embryo transfer rate (45.10% vs. 18.52%, P = 0.020) and implantation rate (58.23% vs. 34.69%, P = 0.010). From day –1 to day 1, osmolality increased, with the P-3.5 group showing a significant elevation compared to the other three groups. After 5 days of incubation, the osmotic pressure of group R-4.0 was significantly lower than that of groups P-3.5, P-4.0 and P-3.5. In conclusion, refrigerated culture media dishes helped stabilize the osmotic pressure of the culture microenvironment and reduce water evaporation. The refrigerated group showed a higher rate of high-quality embryos and live births, although pre-warmed culture media effectively reduced the occurrence of air microbubbles that affect embryo imaging in the next day’s dishes.
A species of acanthocephalan collected from the hindgut of Larimichthys crocea was identified as Longicollum pagrosomi Yamaguti, 1935 based on morphological characteristics. The complete mitochondrial genome of this parasite was sequenced. The mitogenome exhibited a circular structure with a total length of 14 632 bp, containing 12 protein coding genes (PCGs), 2 ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs) and 2 major non-coding regions. The most frequently used start codon was GTG, and the most abundant amino acid was valine. The phylogenetic analyses of the mitogenome using Bayesian inference and maximum likelihood methods showed that the genus Longicollum formed a sister clade to the genus Pomphorhynchus, supporting the monophyly of Pomphorhynchus. This study reported a new host for L. pagrosomi and revealed the first complete mitogenome sequence of the genus Longicollum.
Clinical high risk for psychosis (CHR) is often managed with antipsychotic medications, but their effects on neurocognitive performance and clinical outcomes remain insufficiently explored. This study investigates the association between aripiprazole and olanzapine use and cognitive and clinical outcomes in CHR individuals, compared to those receiving no antipsychotic treatment.
Methods
A retrospective analysis was conducted on 127 participants from the Shanghai At Risk for Psychosis (SHARP) cohort, categorized into three groups: aripiprazole, olanzapine, and no antipsychotic treatment. Neurocognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB), while clinical symptoms were assessed through the Structured Interview for Prodromal Syndromes (SIPS) at baseline, 8 weeks, and one year.
Results
The non-medicated group demonstrated greater improvements in cognitive performance, clinical symptoms, and functional outcomes compared to the medicated groups. Among the antipsychotic groups, aripiprazole was associated with better visual learning outcomes than olanzapine. Improvements in neurocognition correlated significantly with clinical symptom relief and overall functional gains at follow-up assessments.
Conclusions
These findings suggest potential associations between antipsychotic use and cognitive outcomes in CHR populations while recognizing that observed differences may reflect baseline illness severity rather than medication effects alone. Aripiprazole may offer specific advantages over olanzapine, underscoring the importance of individualized risk-benefit evaluations in treatment planning. Randomized controlled trials are needed to establish causality.
This paper presents an investigation of the secondary saturation characteristics of a HfTe2 saturable absorber. Pulse energies of 5.85 and 7.4 mJ were demonstrated with a high-order Hermite–Gaussian (HG) laser and a vortex laser, respectively, using alexandrite as the gain medium. To the best of our knowledge, these are the highest pulse energies directly generated with HG and vortex lasers. To broaden the applications of high-energy pulsed HG and vortex lasers, wavelength tuning in the region of 40 nm was achieved using an etalon.
We document numerous occurrences of pump-and-dump schemes (P&Ds) targeting cryptocurrencies, which tend to trigger short-term episodes that feature dramatic increases in prices, volume, and volatility, followed by quick reversals. The evidence we document, including price run-ups before P&Ds start, suggests wealth transfers from outsiders to insiders. Our findings based on wallet-level data are consistent with the reasoning that gambling preferences, overconfidence, and naïve reinforcement learning help explain P&D participation. Finally, exploiting two natural experiments in which exchanges altered P&D policies, we find evidence consistent with the idea that P&Ds contribute to reduced cryptocurrency liquidity and lower prices.
Myocardial bridge contributes to chest pain, often accompanied by non-specific complaints.
Aims
Our study aims to determine somatic symptom disorder (SSD) prevalence in patients with myocardial bridge, investigating associated clinical and psychological features.
Method
In this prospective cross-sectional study, we enrolled 1357 participants (337 with and 1020 without myocardial bridge) from Shanghai Renji Hospital. The Somatic Symptom Scale-China questionnaire was used to assess SSD. Depressive and anxiety disorders were assessed by the Patient Health Questionnaire-9 (PHQ-9) and Generalised Anxiety Disorder-7 (GAD-7).
Results
The prevalence of SSD in the myocardial bridge group was 63.2%, higher than the group without myocardial bridge (53.8%). Patients with myocardial bridge were at an increased risk of SSD (odds ratio 1.362, 95% CI 1.026–1.809; P = 0.033). There were no differences in the mean PHQ-9 scores (3.2 ± 3.4 v. 3.2 ± 4.1; P = 0.751) or GAD-7 scores (2.5 ± 3.0 v. 2.3 ± 3.7; P = 0.143) between the two groups. Among patients with myocardial bridge, gender was the only independent risk factor for SSD. Women were 3.119 times more likely to experience SSD compared with men (95% CI 1.537–6.329; P = 0.002).
Conclusions
Our findings emphasise the high prevalence and severity of SSD among patients with myocardial bridge. The screening for SSD should be of particular concern, especially among female patients.
Machine learning has already shown promising potential in tiled-aperture coherent beam combining (CBC) to achieve versatile advanced applications. By sampling the spatially separated laser array before the combiner and detuning the optical path delays, deep learning techniques are incorporated into filled-aperture CBC to achieve single-step phase control. The neural network is trained with far-field diffractive patterns at the defocus plane to establish one-to-one phase-intensity mapping, and the phase prediction accuracy is significantly enhanced thanks to the strategies of sin-cos loss function and two-layer output of the phase vector that are adopted to resolve the phase discontinuity issue. The results indicate that the trained network can predict phases with improved accuracy, and phase-locking of nine-channel filled-aperture CBC has been numerically demonstrated in a single step with a residual phase of λ/70. To the best of our knowledge, this is the first time that machine learning has been made feasible in filled-aperture CBC laser systems.
Cleavers, an annual or winter annual broadleaf weed in the Rubiaceae family, has become troublesome in the wheat fields of the Huang-Huai-Hai region in China due to its herbicide resistance. In North America the common name of the plant is stickwilly; in China it known as cleavers. Four populations of cleavers (JS-15, SD-10, JS-22, and AH-20) were collected from wheat fields in Jiangsu, Shandong, and Anhui provinces, where the plant was not being controlled with applications of florasulam. The aims of this study were to identify the herbicide resistance patterns and investigate the mechanism underlying florasulam resistance. Whole-plant dose-response experiments revealed a notable variation in the degree of resistance exhibited by three specific populations toward florasulam, in comparison to the most sensitive population (S and AH-9), with the highest resistance index reaching 841.4. A gene-sequencing assay for acetolactate synthase (ALS) found that plants that were resistant to ALS from the JS-15, JS-22, and AH-20 populations had a Trp-574-Leu mutation, while no known ALS resistance mutations were discovered in SD-10 plants. In vitro ALS enzyme activity assays also indicated that the extractable ALS from JS-15, JS-22, and AH-20 plants was greatly resistant to florasulam relative to plants that are susceptible. Additionally, according to the resistance rating system, all resistant populations were susceptible to carfentrazone-ethyl + MCPA-sodium and bipyrazone + fluroxypyr-methyl. AH-20, JS-15, and JS-22 exhibited resistance to selected ALS, 4-hydroxyphenylpyruvate dioxygenase (HPPD), and photosystem II (PS II) complex inhibitors, demonstrating RR and RRR resistance profiles, whereas AH-9 displayed sensitivity to virtually all tested agents. The SD-10 population, on the other hand, exhibited RR and RRR resistance to HPPD and PS II inhibitors, and sensitivity to tribenuron-methyl. These findings indicate that a target site–based mechanism drives resistance to the ALS inhibitor florasulam in populations of cleavers, but nontarget site resistance may also have contributed to resistance, but this was not investigated. Other herbicides with different sites of action were tested and were active against cleavers.
This chapter reviews alternative methods for estimating the integrated covariance matrix (ICM) using high-frequency data and their properties. The high-frequency data are assumed to come from a continuous-time model. The alternative estimators are justified by their asymptotic properties under the infill asymptotic scheme, which requires that the time interval Δ between any two consecutive observations go to zero. When reviewing the methods, we separate the methods that assume the dimension of the ICM is fixed and those that assume the dimension of the ICM goes to infinity with the sample size. Comparisons of the performances of alternative ICM estimators in portfolio choice are discussed.
In the presence of bubbles, asset prices consist of a fundamental and a component, with the bubble component following an explosive dynamic. The general idea for bubble identification is to apply explosive root tests to a proxy of the unobservable bubble. This chapter provides a theoretical framework that incorporates several definitions of bubbles (and fundamentals) and offers guidance for selecting proxies. For explosive root tests, we introduce the recursive evolving test of Phillips, Shi, and Yu (2015a,b) along with its asymptotic properties. This procedure can serve as a real-time monitoring device and has been shown to outperform several other tests. Like all other recursive testing procedures, the PSY algorithm faces the issue of multiplicity in testing. We propose a multiple-testing algorithm to determine appropriate test critical values and show its satisfactory performance in finite samples by simulations. To illustrate, we conduct a pseudo real-time bubble monitoring exercise in the S&P 500 stock market from January 1990 to June 2020. The empirical results reveal the importance of using a good proxy for bubbles and addressing the multiplicity issue.
This chapter provides an overview of posterior-based specification testing methods and model selection criteria that have been developed in recent years. For the specification testing methods, the first method is the posterior-based version of IOSA test. The second method is motivated by the power enhancement technique. For the model selection criteria, we first review the deviance information criterion (DIC). We discuss its asymptotic justification and shed light on the circumstances in which DIC fails to work. One practically relevant circumstance is when there are latent variables that are treated as parameters. Another important circumstance is when the candidate model is misspecified. We then review DICL for latent variable models and DICM for misspecified models.