Impact of Chemotherapy Regimens on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Rectal Cancer Patients Receiving Intensity Modulated Radiation Therapy With Concurrent Chemotherapy From a Prospective Phase III Clinical Trial

Purpose: To determine whether there are differences in bone marrow tolerance to chemoradiotherapy (CRT) between two chemotherapy regimens according to FOWARC protocol and how chemotherapy regimens affect radiation dose parameters and normal tissue complication probability (NTCP) modelings that correlate with acute hematologic toxicity (HT) in rectal cancer patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy.Materials and Methods: One hundred and twenty-eight rectal cancer patients who received IMRT from a single institution were recruited from Chinese FOWARC multicenter, open-label, randomized phase III trial. We assessed HT in these patients who were separated into two groups: Oxaliplatin (L-OHP) + 5- fluorouracil (5FU) (FOLFOX, 70 of 128) and 5FU (58 of 128). The pelvic bone marrow (PBM) was divided into three subsites: lumbosacral spine (LSS), ilium (I), and lower pelvic (LP). The endpoint for HT was grade ≥3 (HT3+) and grade ≥2 (HT2+) leukopenia, neutropenia, anemia and thrombocytopenia. Logistic regression was used to analyze the association between HT2+/HT3+ and dosimetric parameters. Lyman-Kutcher-Burman (LKB) model was used to calculate NTCP.Results: Sixty-eight patients experienced HT2+: 22 of 58 (37.9%) 5FU and 46 of 70 (65.7%) FOLFOX (p = 0.008), while twenty-six patients experienced HT3+: 4 of 58 (6.9%) 5FU and 22 of 70 (31.4%) FOLFOX (p = 0.016). PBM and LP dosimetric parameters were correlated with HT2+ in the 5FU group but not in the FOLFOX group. No PBM dosimetric parameters were correlated with HT3+ in both groups. For PBM, NTCP at HT3+ was 0.32 in FOLFOX group relative to 0.10 in 5FU subset (p < 0.05).Conclusion: Patients receiving FOLFOX have lower BM tolerance to CRT than those receiving 5FU. Low-dose radiation to the PBM is predictive for HT2+ in patients who received 5FU. NTCP modeling in FOLFOX group predicts much higher risk of HT3+ than 5FU group

Microglia and Microglia-Like Cell Differentiated from DC Inhibit CD4 T Cell Proliferation

The central nervous system (CNS) is generally regarded as a site of immune privilege, whether the antigen presenting cells (APCs) are involved in the immune homeostasis of the CNS is largely unknown. Microglia and DCs are major APCs in physiological and pathological conditions, respectively. In this work, primary microglia and microglia-like cells obtained by co-culturing mature dendritic cells with CNS endothelial cells in vitro were functional evaluated. We found that microglia not only cannot prime CD4 T cells but also inhibit mature DCs (maDCs) initiated CD4 T cells proliferation. More importantly, endothelia from the CNS can differentiate maDCs into microglia-like cells (MLCs), which possess similar phenotype and immune inhibitory function as microglia. Soluble factors including NO lie behind the suppression of CD4 T cell proliferation induced by both microglia and MLCs. All the data indicate that under physiological conditions, microglia play important roles in maintaining immune homeostasis of the CNS, whereas in a pathological situation, the infiltrated DCs can be educated by the local microenvironment and differentiate into MLCs with inhibitory function

Risk-preference–driven participate willingness provides alternative routes to solve social dilemma

Risk preference is the level of risk that a person is prepared to accept when pursuing his goals. In economic interaction, risk preference determines willingness to participate and affects the evolution of cooperation. In particular, most people may take a moderate attitude towards the risk and only choose to participate in part. Based on such reality, this work abstracts this behavior as a partial cooperation strategy and analyzes the evolution of cooperation. Essentially, partial cooperation is a balance between participation and non-participation by the cooperator. From the micro-dynamic characteristics of the simulation results, the partial cooperation players play different roles in the dynamic system. Specifically, when the willingness to participate is insufficient (sufficient), these partial cooperation players will replace the position of the loners (cooperators) in the evolutionary dynamics, which further leads to the special cyclic invasion. Moreover, as the willingness to participate increases, the percentage of free riding (cooperation) for the second time gradually decreases until it disappears

Cumulative advantage is a double-edge sword for cooperation

The Matthew effect emphasizes the influence of early advantage on shaping long-term development by amplifying it over time, and its implications for public cooperation are yet to be fully understood. In this letter, we propose and study a spatial public goods game driven by cumulative advantage, where players who achieve high payoffs in a given round receive greater allocations in the next. The simulation results show that the Matthew effect leads to an irreversible polarization of individual wealth on the network. Such polarization makes moderate cooperation levels more prevalent, which helps to explain the widespread coexistence of prosocial and antisocial behavior. Meanwhile, heterogeneous networks may restrict the polarization of wealth, but also inhibit the evolution of cooperation, requiring a reconsideration of the commonly held view that heterogeneous networks enhance cooperation

Fast and Arbitrary Beam Pattern Design for RIS-Assisted Terahertz Wireless Communication

Reconfigurable intelligent surface (RIS) can assist terahertz wireless communication to restore the fragile line-of-sight links and facilitate beam steering. Arbitrary reflection beam patterns are desired to meet diverse requirements in different applications. This paper establishes relationship between RIS beam pattern design with two-dimensional finite impulse response filter design and proposes a fast non-iterative algorithm to solve the problem. Simulations show that the proposed method outperforms baseline method. Hence, it represents a promising solution for fast and arbitrary beam pattern design in RIS-assisted terahertz wireless communication.Comment: 5 pages, 5 figure

Tumor microenvironment-activated theranostic nanoreactor for NIR-II photoacoustic imaging-guided tumor-specific photothermal therapy

Theranostic agents that can be sensitively and specifically activated by the tumor microenvironment (TME) have recently attracted considerable attention. In this study, TME-activatable 3,3′,5,5′-tetramethylbenzidine (TMB)-copper peroxide (CuO2)@poly(lactic-co-glycolic acid) (PLGA)@red blood cell membrane (RBCM) (TCPR) nanoparticles (NPs) for second near-infrared photoacoustic imaging-guided tumor-specific photothermal therapy were developed by co-loading CuO2 NPs and TMB into PLGA camouflaged by RBCMs. As an efficient H2O2 supplier, once exposed to a proton-rich TME, CuO2 NPs can generate H2O2 and Cu2+, which are further reduced to Cu+ by endogenous glutathione. Subsequently, the Cu+-mediated Fenton-like reaction produces cytotoxic ·OH to kill the cancer cells and induce TMB-mediated photoacoustic and photothermal effects. Combined with the RBCM modification-prolonged blood circulation, TCPR NPs display excellent specificity and efficiency in suppressing tumor growth, paving the way for more accurate, safe, and efficient cancer theranostics.Published versionThis work was supported by the National Natural Science Foundation (NNSF) of China (Grant Nos.: 62120106002, 51803091, 61935004, 22175089), Jiangsu Province Policy Guidance Plan (BZ2019014), Jiangsu Provincial key research and development plan (BE2021711), NSF of Shandong Province (ZR2020KB018), Taishan scholars construction special fund of Shandong Province, Natural Science Foundation of Ningbo (202003N40448), and the Jiangsu postgraduate research innovation program (KYCX21_1103)

Driving anger and its relationships with type A behavior patterns and trait anger: Differences between professional and non-professional drivers

<div><p>The present study examined the types of situations that caused Chinese professional and non-professional drivers to become angry and investigated the differences in driving-elicited anger, considering the influences of type A behavior pattern and trait anger between the two groups. The 20-item revised Driving Anger Scale (DAS) was used to assess a sample of 232 drivers (57% professional, 43% non-professional). The non-professional drivers reported significantly higher levels of anger than the professional drivers on the overall Driving Anger Scale (DAS) and the traffic obstructions and discourtesy subscales. In both groups, the preferred driving speeds were positively related to driving anger. Furthermore, drivers with a type A personality exhibited higher overall driving anger scores and higher anger scores in response to traffic obstructions and slow driving than drivers with a type B personality. Trait anger was significantly related to driving anger in both groups. In the non-professional group, type A behavior patterns (TABPs) and time hurry (TH) were positively correlated with anger evoked by slow driving. In the professional group, TABPs, TH and competitive hostility (CH) were positively related to driving anger, and the TABPs exerted an indirect effect on driving anger by mediating the influence of trait anger. Overall, these findings provide a theoretical basis for implementing targeted interventions for driving anger in both professional and non-professional drivers.</p></div

A model of dynamic transformation of antigen presenting cells in CNS.

<p>Some special infection in the CNS can destroy neural tissues and endothelial cells of capillary, in this status, BBB was impaired followed by the entrance of monocytes and autoreactive T cells from peripheral blood. Monocytes will become mature DCs in the stimulation of inflammation factors secreted by the infected cells, after crossing the endothelia. New mature DCs derived from monocytes will capture the antigens of neural tissue, prime autoreactive T cells and lead to immunopathological injury. On the contrary, microglia activated by the inflammation factors can secrete high level of NO to inhibit T cell proliferation, even induce T cell apoptosis. The role of IL-10 secreted by microglia in the inhibitory function remains to be investigated. The infiltrated dendritic cells after priming might become inhibitory microglia like cells or microglia under the sustained influence of microenvironment. The cell-to-cell interaction played a key role in the differentiation of DC. The effects of TGF-β, M-CSF, VEGF secreted by activated endothelial cells remain to be investigated. Whether MLC will differentiate into microglia is unknown. Microglia and the transformation from priming dendritic cells to inhibitory microglia like cells and even microglia contribute to the remission of the autoimmune diseases of CNS.</p