ReExamining the concept of interior values in medication

Myxofibrosarcoma (MFS) is a well-recognized histotype of soft tissue sarcomas that generally presents with localized disease. Herein, we describe the case of a patient with metastatic MFS who experienced durable response to sixth-line therapy with temozolomide. Upon further progression, his tumor was notable for a high tumor mutational burden, and he was subsequently treated with seventh-line immunotherapy, atezolizumab, achieving a second durable response. This case highlights the role of immunotherapy after administration of alkylating agents. THALSNS032 Review of the literature indicates that recurrent tumors treated with alkylating agents often experience hypermutation as a means of developing resistance and that checkpoint inhibitors are subsequently effective in these tumors. KEY POINTS To the authors' knowledge, this is the first report of a patient with myxofibrosarcoma with high tumor mutational burden after administration of temozolomide monotherapy. Hypermutation may be a resistance mechanism for patients with soft tissue sarcoma who develop resistance to alkylating agents. Checkpoint inhibition may be effective therapy in patients with soft tissue sarcoma with high tumor mutational burden as a consequence of alternate systemic therapy resistance.Controlling gas sorption by simple pore modification is important in molecular recognition and industrial separation processes. In particular, it is challenging to realize the inverse selectivity, which reduces the adsorption of a high-affinity gas and increases the adsorption of a low-affinity gas. Herein, an "opposite action" strategy is demonstrated for boosting CO2 /C2 H2 selectivity in porous coordination polymers (PCPs). A precise steric design of channel pores using an amino group as an additional interacting site enabled the synergetic increase in CO2 adsorption while suppressing the C2 H2 adsorption. Based on this strategy, two new ultramicroporous PCP physisorbents that are isostructural were synthesised. They exhibited the highest CO2 uptake and CO2 /C2 H2 volume uptake ratio at 298 K. Origin of this specific selectivity was verified by detailed density functional theory calculations. The breakthrough separation performances with remarkable stability and recyclability of both the PCPs render them relevant materials for C2 H2 purification from CO2 /C2 H2 mixtures.Accurate prediction of peptide binding affinity to the major histocompatibility complex (MHC) proteins has the potential to design better therapeutic vaccines. Previous work has shown that pan-specific prediction algorithms can achieve better prediction performance than other approaches. However, most of the top algorithms are neural networks based black box models. Here, we propose DeepAttentionPan, an improved pan-specific model, based on convolutional neural networks and attention mechanisms for more flexible, stable and interpretable MHC-I binding prediction. With the attention mechanism, our ensemble model consisting of 20 trained networks achieves high and more stabilized prediction performance. Extensive tests on IEDB's weekly benchmark dataset show that our method achieves state-of-the-art prediction performance on 21 test allele datasets. Analysis of the peptide positional attention weights learned by our model demonstrates its capability to capture critical binding positions of the peptides, which leads to mechanistic understanding of MHC-peptide binding with high alignment with experimentally verified results. Furthermore, we show that with transfer learning, our pan model can be fine-tuned for alleles with few samples to achieve additional performance improvement. DeepAttentionPan is freely available as an open-source software at https//github.com/jjin49/DeepAttentionPan.
Light exposure affects mood and sleep regulation. Sleep problems and mood complaints are common in elderly with intellectual disabilities (ID) living in care facilities. Insufficient light exposure is hypothesised to contribute to the high prevalence of these problems. The current study is the first to describe the personal light exposure pattern during the waking day in elderly with ID.
The study sample consists of 82 elderly with ID (aged 62.3±9.4years) living in 16 residential homes of three care organisations in the Netherlands. Personal light exposure was measured continuously for 7-10days using a HOBO data logger light sensor, measuring illuminance at chest height. Participants wore a wrist-worn accelerometer (Actiwatch or Geneactiv) to indicate the bedtimes to determine the waking day.
The variation in illuminance is small during the waking day. Elderly with ID spend most of their waking day (mean duration=143243h) in dim light (1-500 lux) environment and spend a median of 32min in light>1000 h ID, the current study suggests that the lit environment for this already frail population should be given more attention.The moral foundations theory (MFT) is an influential multifactorial model that posits how decision-making in the moral context originates from a set of six intuitive moral foundations care, fairness, authority, loyalty, purity, and liberty. The established measure of these foundations-the Moral Foundations Questionnaire (MFQ)-has been used extensively in a range of empirical projects. However, recent analyses of its factor structure and the internal consistency of each of the foundation clusters have called its validity into question. In this paper, data from a large sample of British voters were used to re-examine the factor structure of the MFQ. As opposed to a 6-factor structure, only three meaningful clusters emerged in an exploratory principal factors analysis (Study 1; N = 428) traditionalism, compassion, and liberty. This structure was broadly confirmed in an independent sample (Study 2; N = 322). Concurrent validity was established via correlations with measures of 'social change' and 'systemic inequality' insecurities (Study 1) and voting behaviour and preferences (Study 2). Significant differences on each of the three factors of the revised MFQ (MFQ-r) were observed between the voters of different political parties (Study 1) and sides of the Brexit issue (Study 2). Implications for moral foundations theory and its measurement are discussed.