Too Much of a Good Thing: Attention Misallocation and Social Welfare in Coordination Games

This paper examines the welfare properties of “beauty contest” games with rationally inattentive agents. Agents allocate attention between private and public signals to reduce the uncertainty about observation noises. In this setting, social welfare may not necessarily increase with the capacity to process information, and can actually decrease as a result of attention misallocation. Strikingly, social welfare can be even higher when agents possess a finite amount of capacity than when they have an infinite amount of capacity. We derive sufficient and necessary conditions under which multiple equilibria emerge and study the implications of equilibrium multiplicity for macroeconomic policies

The metabolic repression effect of carbon-ion radiotherapy in synchronous hormone-sensitive oligometastatic prostate cancer

BackgroundMetastatic prostate cancer (PCa) poses a significant public health concern. While radiation therapy (RT) is commonly utilized in the treatment of synchronous oligometastatic hormone sensitive prostate cancer (OM-HSPC), the occurrence of biochemical recurrence still remains. To deepen our understanding and optimize the outcome of OM-HSPC, we conducted this study to investigate the characteristics of PCa progression and explore potential synergistic mechanisms involving carbon-ion radiotherapy (CIRT) and neoadjuvant androgen deprivation treatment (naADT) in OM-HSPC.MethodsMetabolomic analysis was conducted with 72 urinary samples (at different timepoints) from 33 Patients (T2-3N0M0-1b) and 18 healthy volunteers by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). MetaboAnalyst website and R software were employed for metabolomic analysis and visualization (using the criteria of p value < 0.05 and |FC|>1.5). The impact of CIRT on metabolism were further verified and explored through in vitro and in vivo experiments.ResultsWe found that most metabolites (223 out of 233) were upregulated in treatment-naïve PCa samples compared to healthy samples. After naADT, 60 core risk metabolites were still significantly related to PCa’s progression, and the glutamine level which was significantly higher in OM-HSPC compared to other groups. Remarkably, after CIRT treatment, the glutamine levels in OM-HSPC were significantly reduced to the level of healthy samples. Experiments further confirmed CIRT’s ability to suppress glutamine levels in PCa tumors and its potential enhancement with glutamine deprivation intervention.ConclusionCIRT with naADT might synergistically inhibit HS-OMPC development, progression and even the ADT resistance through glutamine metabolism repression, moreover, the glutamine metabolism might be a novel target to further improved the efficacy of CIRT

Carbon Ion Radiotherapy Induce Metabolic Inhibition After Functional Imaging-Guided Simultaneous Integrated Boost for Prostate Cancer

PurposeAs local recurrence remains a challenge and the advantages of the simultaneous integrated boost (SIB) technique have been validated in photon radiotherapy, we applied the SIB technique to CIRT. The aim was to investigate the metabolomic changes of the CIRT with concurrent androgen deprivation therapy (ADT) in localized prostate cancer (PCa) and the unique metabolic effect of the SIB technique.Material and MethodsThis study enrolled 24 pathologically confirmed PCa patients. All patients went through CIRT with concurrent ADT. The gross target volume (GTV) boost was defined as positive lesions on both 68Ga-PSMA PET/CT and mpMRI images. Urine samples collected before and after CIRT were analyzed by the Q-TOF UPLC-MS/MS system. R platform and MetDNA were used for peak detection and identification. Statistical analysis and metabolic pathway analysis were performed on Metaboanalyst.ResultsThe metabolite profiles were significantly altered after CIRT. The most significantly altered metabolic pathway is PSMA participated alanine, aspartate and glutamate metabolism. Metabolites in this pathway showed a trend to be better suppressed in the SIB group. A total of 11 identified metabolites were significantly discriminative between two groups and all of them were better down-regulated in the SIB group. Meanwhile, among these metabolites, three metabolites in DNA damage and repair related purine metabolism were down-regulated to a greater extent in the SIB group.ConclusionMetabolic dysfunction was one of the typical characteristics of PCa. CIRT with ADT showed a powerful inhibition of PCa metabolism, especially in PSMA participated metabolic pathway. The SIB CIRT showed even better performance on down-regulation of most metabolism than uniform-dose-distribution CIRT. Meanwhile, the SIB CIRT also showed its unique superiority to inhibit purine metabolism. PSMA PET/CT guided SIB CIRT showed its potentials to further benefit PCa patients

Erythritol attenuates postprandial blood glucose by inhibiting α-glucosidase

This work was supported by grants from Natural Science Foundation of Qinghai (No. 2016-ZJ-942Q), West Light Foundation of the Chinese Academy of Sciences (No. Y629071211), National Natural Science Foundation of China (No. 31701243), International Cooperative Projects of Qinghai province (No. 2017-HZ-811), Project of Discovery, Evaluation and Transformation of Active Natural Compounds, Strategic Biological Resources Service Network Program of Chinese Academy of Sciences (No. ZSTH-027), Major Special Science and Technology Projects in Qinghai Province (2014-GX-A3A-01).Diabetes mellitus (DM) is a serious metabolic disorder where impaired postprandial blood glucose regulation often leads to severe health complications. The natural chemical, erythritol is a C4 polyol approved by FDA for use as a sweetener. Here we examined a potential role for erythritol in the control of postprandial blood glucose levels in DM. An anti-postprandial hyperglycemia effect upon erythritol administration (500 mg kg-1) was demonstrated in alloxan-induced DM model mice by monitoring changes in blood glucose after intragastric administration of drugs and starch. We also found that erythritol most likely exerts its anti-postprandial hyperglycemic activities by inhibiting α-glucosidase in a competitive manner. This was supported by enzyme activity assays and molecular modelling experiments. In the latter experiments it was possible to successful dock erythritol into the catalytic pocket of α-glucosidase, with the resultant interaction likely to be driven by electrostatic interactions involving Asp 215, Asp69 and Arg446 residues. This study suggests that erythritol may not only serve as a glucose substitute but may also be a useful agent in the treatment of diabetes mellitus to help manage postprandial blood glucose levels.PostprintPeer reviewe

Multi-site, Multi-domain Airway Tree Modeling (ATM'22): A Public Benchmark for Pulmonary Airway Segmentation

Open international challenges are becoming the de facto standard for assessing computer vision and image analysis algorithms. In recent years, new methods have extended the reach of pulmonary airway segmentation that is closer to the limit of image resolution. Since EXACT'09 pulmonary airway segmentation, limited effort has been directed to quantitative comparison of newly emerged algorithms driven by the maturity of deep learning based approaches and clinical drive for resolving finer details of distal airways for early intervention of pulmonary diseases. Thus far, public annotated datasets are extremely limited, hindering the development of data-driven methods and detailed performance evaluation of new algorithms. To provide a benchmark for the medical imaging community, we organized the Multi-site, Multi-domain Airway Tree Modeling (ATM'22), which was held as an official challenge event during the MICCAI 2022 conference. ATM'22 provides large-scale CT scans with detailed pulmonary airway annotation, including 500 CT scans (300 for training, 50 for validation, and 150 for testing). The dataset was collected from different sites and it further included a portion of noisy COVID-19 CTs with ground-glass opacity and consolidation. Twenty-three teams participated in the entire phase of the challenge and the algorithms for the top ten teams are reviewed in this paper. Quantitative and qualitative results revealed that deep learning models embedded with the topological continuity enhancement achieved superior performance in general. ATM'22 challenge holds as an open-call design, the training data and the gold standard evaluation are available upon successful registration via its homepage.Comment: 32 pages, 16 figures. Homepage: https://atm22.grand-challenge.org/. Submitte

Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters

Transcription of long noncoding RNAs (lncRNAs) within gene regulatory elements can modulate gene activity in response to external stimuli, but the scope and functions of such activity are not known. Here we use an ultrahigh-density array that tiles the promoters of 56 cell-cycle genes to interrogate 108 samples representing diverse perturbations. We identify 216 transcribed regions that encode putative lncRNAs, many with RT-PCR–validated periodic expression during the cell cycle, show altered expression in human cancers and are regulated in expression by specific oncogenic stimuli, stem cell differentiation or DNA damage. DNA damage induces five lncRNAs from the CDKN1A promoter, and one such lncRNA, named PANDA, is induced in a p53-dependent manner. PANDA interacts with the transcription factor NF-YA to limit expression of pro-apoptotic genes; PANDA depletion markedly sensitized human fibroblasts to apoptosis by doxorubicin. These findings suggest potentially widespread roles for promoter lncRNAs in cell-growth control.National Institutes of Health (U.S.)National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (NIAMS) (K08-AR054615))National Cancer Institute (U.S.) (NIH/(NCI) (R01-CA118750))National Cancer Institute (U.S.) (NIH/(NCI) R01-CA130795))Juvenile Diabetes Research Foundation InternationalAmerican Cancer SocietyHoward Hughes Medical Institute (Early career scientist)Stanford University (Graduate Fellowship)National Science Foundation (U.S.) (Graduate Research Fellowship)United States. Dept. of Defense (National Defense Science and Engineering Graduate Fellowship

Attention misallocation, social welfare and policy implications

We examine how agents allocate attention between private and public signals to reduce the uncertainty about observation noises when coordination is an important concern. In this setting, the attention allocation may not be monotone in endowed attention capacity. Agents may decrease their attention on or even ignore the more accurate signal when capacity increases. As a result, social welfare may decrease when they have more attention to process information. And it can be even higher when agents possess a finite amount of capacity than when they have an infinite amount of capacity. We derive sufficient and necessary conditions under which multiple equilibria emerge and study the implications of equilibrium multiplicity for macroeconomic policies

Biological and clinical significance of radiomics features obtained from magnetic resonance imaging preceding pre-carbon ion radiotherapy in prostate cancer based on radiometabolomics

IntroductionWe aimed to investigate the feasibility of metabolomics to explain the underlying biological implications of radiomics features obtained from magnetic resonance imaging (MRI) preceding carbon ion radiotherapy (CIRT) in patients with prostate cancer and to further explore the clinical significance of radiomics features on the prognosis of patients, based on their biochemical recurrence (BCR) status.MethodsMetabolomic results obtained using high-performance liquid chromatography coupled with tandem mass spectrometry of urine samples, combined with pre-RT radiomic features extracted from MRI images, were evaluated to investigate their biological significance. Receiver operating characteristic (ROC) curve analysis was subsequently conducted to examine the correlation between these biological implications and clinical BCR status. Statistical and metabolic pathway analyses were performed using MetaboAnalyst and R software.ResultsCorrelation analysis revealed that methionine alteration extent was significantly related to four radiomic features (Contrast, Difference Variance, Small Dependence High Gray Level Emphasis, and Mean Absolute Deviation), which were significantly correlated with BCR status. The area under the curve (AUC) for BCR prediction of these four radiomic features ranged from 0.704 to 0.769, suggesting that the higher the value of these four radiomic features, the greater the decrease in methionine levels after CIRT and the lower the probability of BCR. Pre-CIRT MRI radiomic features were associated with CIRT-suppressed metabolites.DiscussionThese radiomic features can be used to predict the alteration in the amplitude of methionine after CIRT and the BCR status, which may contribute to the optimization of the CIRT strategy and deepen the understanding of PCa

Evaluating the Roles of sCD14 and sCD14-ST in Diagnosing COPD and Predicting an Acute Exacerbation of COPD

Abstract Aim To evaluate the roles of plasma soluble cluster of differentiation 14 (sCD14) and sCD14 subtype (sCD14-ST) in the diagnosis of chronic obstructive pulmonary disease (COPD) and in the prediction of an acute exacerbation of COPD (AECOPD). Methods We quantified the levels of white blood cell count (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin (IL)-6, IL-8, sCD14, and sCD14-ST in patients with COPD and healthy controls. The relationships between sCD14 or sCD14-ST and inflammatory markers were analyzed in each group. We used receiver operating characteristics (ROC) curves to evaluate the potential roles of sCD14 and sCD14-ST in the diagnosis of COPD and in predicting AECOPD. Results A total of 62 subjects were recruited, including 15 controls and 47 COPD patients, with the latter including 32 stable COPD and 15 AECOPD. WBC, IL-8, sCD14, and sCD14-ST were significantly higher in COPD than in the controls (all P < 0.05). WBC, CRP, ESR, IL-6, IL-8, sCD14, and sCD14-ST were higher in AECOPD than in the controls (all P < 0.05). In the COPD group, sCD14 levels were positively correlated with WBC, IL-8, and sCD14-ST (P < 0.05), and sCD14-ST levels were positively correlated with WBC and IL-8 (P < 0.05). In the AECOPD group, sCD14 was positively correlated with WBC, CRP, IL-8, and sCD14-ST (P < 0.05); sCD14-ST was positively correlated with WBC, IL-6, and IL-8 (P < 0.05). Discrimination between COPD and controls was tested by calculating areas under the ROC curve (AUCs) for sCD14 and sCD14-ST showing scores of 0.765 (95% CI 0.648–0.883) and 0.735 (95% CI 0.537–0.933) respectively. Similarly, discrimination between AECOPD and controls using sCD14 and sCD14-ST showed scores of 0.862 (95% CI 0.714–1.000) and 0.773 (95% CI 0.587–0.960), respectively. Conclusion Our study suggests that the inflammatory markers sCD14 and sCD14-ST might play an important diagnostic role in COPD and help predict AECOPD

“Three birds with one stone” nanoplatform: Efficient near‐infrared‐triggered type‑I AIE photosensitizer for mitochondria‐targeted photodynamic therapy against hypoxic tumors

Currently three major problems seriously limit the practical application of cancer photodynamic therapy (PDT): (i) the hypoxic tumor microenvironment (TME); (ii) low generation efficiency of toxic reactive oxygen species (ROS) in aggregates and (iii) shallow tissue penetration depth of excitation light. Very limited approaches are available for addressing all the above three problems with a single design. Herein, a rational “three birds with one stone” molecular and nanoengineering strategy is demonstrated: a photodynamic nanoplatform U‐Ir@PAA‐ABS based on the covalent combination of lanthanide‐doped upconversion nanoparticles (UCNPs) and an AIE‐active dinuclear Ir(III) complex provides a low oxygen concentration‐dependent type‐I photochemical process upon 980 nm irradiation by Föster resonance energy transfer (FRET). U‐Ir@PAA‐ABS targets mitochondria and has excellent phototoxicity even in severe hypoxia environments upon 980 nm irradiation, inducing a dual‐mode cell death mechanism by apoptosis and ferroptosis. Taken together, the in vitro and in vivo results demonstrate a successful strategy for improving the efficacy of PDT against hypoxic tumors