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Using a video game platform, we examined how vision-based decision making was affected by a concurrent, potentially conflicting auditory stimulus. Electroencephalographic responses showed that by 150 milliseconds of stimulus onset, the brain had detected the conflict between visual and auditory stimuli. Systematically reducing the intertrial interval (ITI), which subjects described as stressful, undermined decision making. Subjects’ arterial pulse variance decreased along with ITI, signaling increased parasympathetic influence on the heart. When successive trials required a shift in processing mode, short ITIs significantly boosted one trial’s influence on the next, suggesting that stress reduces cognitive flexibility. Finally, our study demonstrates the heart’s and the brain’s important influence on decision making.

BackgroundAn open, observational, three-arm clinical study aimed at investigating the efficacy of different neoadjuvant therapies (neoadjuvant immunotherapy with(out) chemotherapy, neoadjuvant chemotherapy, and neoadjuvant targeted therapy) in operable locally advanced non-small cell lung cancer (NSCLC) was conducted (NCT04197076). We report an interim analysis of 49 of 53 evaluable patients.MethodsThis study was conducted at Shanghai Chest Hospital and included eligible NSCLC patients who were 18 years old and had clinical stage IIB–IIIB disease. All 49 patients had surgical resection within 4–6 weeks after 2–3 cycles of neoadjuvant treatment consisting of immunotherapy (24 patients), chemotherapy (16 patients), and a targeted therapy (9 patients) regimen starting on the first day of each 21-day cycle. Pathologic complete response (pCR) was evaluated as the primary endpoint. Major pathological response (MPR) and tumor regression rate (TRR) were also evaluated.ResultsAn improved pathologic complete response was achieved in the neoadjuvant immunotherapy arm compared with the neoadjuvant chemotherapy arm and neoadjuvant targeted therapy arm [20.8% (5/24) vs. 6.3% (1/16) vs. 0.0% (0/9); P = 0.089, 95% CI 0.138–0.151]. More importantly, we found that the curative effect of the neoadjuvant immunotherapy arm in pCR+MPR was better than that of the neoadjuvant chemotherapy arm and neoadjuvant targeted therapy arm [45.8% (11/24) vs. 18.8% (3/16) vs. 0.0% (0/9); P = 0.006, 95% confidence interval, 0.008–0.012]. Different neoadjuvant therapies had a statistically significant effect on postoperative pathological tumor downstaging (P = 0.017).ConclusionsNeoadjuvant immunotherapy was associated with a trend toward better pCR than the neoadjuvant chemotherapy arm and neoadjuvant targeted therapy. Curative effect (pCR + MPR) was significantly better with neoadjuvant immunotherapy (P = 0.006, 95% confidence interval, 0.008–0.012).Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04197076?recrs=a&cond=NCT04197076&draw=2&rank=1.

The honeybee is a major pollinating insect and plays a vital role in the ecological chain. Therefore, the correct prediction of honeybee population size and optimal beehive configuration is beneficial for developing long-term or phased management plans for bee colonies to obtain high yields of bee products. Through literature analysis, this paper chooses economic benefits and environmental effects as the multiple objectives of the model. The model is also constrained by the maximum number of bees pollinating and the minimum daily pollen consumption of bees to calculate the optimal number of beehives for a given area. In this paper, we adopt the multi-objective equal-weight processing and transform it into a single-objective approach, which is solved using the artificial bee colony algorithm. According to the final calculation, the optimal number of beehives for this area is 54.

Objectives This study is aimed to analyze the survival differences among patients with lung basaloid squamous cell carcinoma (BSCC), keratinizing squamous cell carcinoma (KSCC), and nonkeratinizing squamous cell carcinoma (NKSCC), and explore the prognostic factors of patients with lung BSCC. Materials and Methods We searched the information of 4743 patients with lung SCC between 2005 and 2014 from the SEER database. Propensity score matching (PSM) was used to adjust confounding factors. The overall survival (OS), cancer-specific survival (CSS), and cumulative incidence of cancer-specific mortality (CSM) were estimated with a comparative analysis. A competing risks regression model was conducted to identify the prognostic factors of lung BSCC. Results After PSM, patients with lung BSCC had a higher CSS rate than those with lung KSCC or NKSCC (5-year CSS rate: 50.4 % vs. 37.7 % vs. 38.5 %, p = 0.033 and p = 0.033). The cumulative incidence of CSM was lower for patients with lung BSCC than those with lung KSCC or NKSCC (5-year CSM rate: 46.4 % vs. 56.9 % vs. 56.4 %, p = 0.046 and p = 0.042), which were similar to the results before PSM. As for patients with lung KSCC and NKSCC, there was no survival differences between them (5-year CSS rate: 37.7 % vs. 38.5 %, p = 0.997). The competing risks regression analysis showed that T stage, N stage, M stage and surgery were independent prognostic factors for patients with lung BSCC (all p Conclusions Patients with lung BSCC had a better survival than those with lung KSCC or NKSCC, while no survival differences were found between lung KSCC and NKSCC. T stage, N stage, M stage and surgery were independent prognostic factors for patients with lung BSCC.

Optical microscopy is an essential tool for exploring the structures and activities of cells and tissues. To break the limit of resolution caused by diffraction, researchers have made continuous advances and innovations to improve the resolution of optical microscopy since the 1990s. These contributions, however, still make sub-10[Formula: see text]nm imaging an obstacle. Here, we name a series of technologies as modulated illumination localization microscopy (MILM), which makes ultra-high-resolution imaging practical. Besides, we review the recent progress since 2017 when MINFLUX was proposed and became the inspiration and foundation for the follow-up development of MILM. This review divides MILM into two types: point-scanning and wide-field. The schematics, principles and future research directions of MILM are discussed elaborately.

Patient-derived xenograft (PDX) assay has been widely used in preclinical research in patients with multidrug-resistant lung cancer. One hundred patients with non-small cell lung cancer (NSCLC) were divided into MiniPDX group and conventional group, with 50 cases in each group. The MiniPDX assay was established by enriching high-purity tumor cells using microfluidic technology to detect the drug sensitivity of NSCLC cells. All patients underwent conventional computed tomography (CT) scans of lung and mediastinum at baseline and during follow-up. Kaplan-Meier method was used to compare the overall survival and progression-free survival of two groups. The sensitivity of the same drug in different tumor xenograft varied greatly. The overall survival, progression-free survival, and clinical benefit rate of patients in the MiniPDX-guided chemotherapy group were significantly longer than those in the conventional chemotherapy group. MiniPDX assay may be an effective tool for screening chemotherapy regimens in NSCLC patients.

There is a lack of direct cross-comparison studies in clinical trials between immunotherapy alone and combination treatment, especially in Non-Small Cell Lung Cancer (NSCLC) patients with high PD-L1 expression. To determine if anti-PD-(L)1 antibody combined with chemotherapy is more efficient than immune checkpoint inhibitor (ICI) monotherapy for advanced NSCLC patients in the real-world data. We retrospectively collected 325 patients with advanced NSCLC treated with ICI alone with or without chemotherapy from 11th July 2016 to 26th May 2020 to investigate which treatment scenario is the most efficient, and how clinical factors impact response. Patients with advanced NSCLC were treated with ICI monotherapy (178/325, 54.8%) or in combination with chemotherapy (147/325, 45.2%). The objective response rate and disease control rate were higher in the combination group than the monotherapy group. Patients (including those with distant metastasis) treated with chemo-immunotherapy were associated with a significantly longer median PFS and OS compared with the monotherapy group, irrespective of the PD-L1 expression level and previous treatment lines. No significant increase in the risk of immune-related adverse events (irAEs) was found after combination with chemotherapy (50.6 vs. 57.8%). IrAEs predicted better PFS of immunotherapy in the monotherapy group, especially for patients with late irAEs (after ≥4 cycles). Collectively, we demonstrated that ICI monotherapy plus chemotherapy might have better anti-tumor activity and an acceptable side-effect profile regardless of PD-L1 level or previous treatment lines. Both regimens were well-tolerated and cost-effective, the more efficient is usually recommended.

The E3 ubiquitin ligase RING finger protein 6 (RNF6) is elevated in several cancers, including prostate and colorectal cancers. Here, we extended the finding of elevated RNF6 expression levels and its association with poor prognosis in patients with lung adenocarcinoma (LUAD). Genome-wide RNA sequencing in H3255 cells with RNF6 knockdown, followed by analysis of differentially expressed genes using Clusters of Orthologous Groups and gene set enrichment analysis revealed aberrations in genes related to DNA repair, especially double-strand break (DSB) repair. RNF6 knockdown increased γH2AX foci, a biomarker for DSBs in H3255 and A549 LUAD cells, and enhanced DNA damage induced by chemotherapy in cisplatin-resistant A549/CDDP cells. In a series of experiments in cultured cells, as well as in nude mice carrying xenografts, RNF6 knockdown restored the sensitivity of A549/CDDP cells to cisplatin treatment. Mechanistically, RNA sequencing in RNF6-knockdown cells revealed the significant downregulation of proliferating cell nuclear antigen (PCNA), an oncogene that promotes DNA repair. Re-chromatin immunoprecipitation assay results suggested the formation of a RNF6-TCF4 complex that binds to the PCNA promoter to activate its transcription. Downregulation of RNF6 reduced TCF4 recruitment to PCNA promoters in H3255 and A549 cells, indicating that RNF6 regulates PCNA transcription to a certain extent by regulating TCF4 binding to PCNA promoters. The collective results implicate RNF6 overexpression as a molecular target in the management of cisplatin-resistant LUAD.

Aberrations in epigenetic modulation dysregulate transcription, playing a critical role in the developmental process of tumors, including lung cancer. Aberrant levels of the histone 3 lysine-27 demethylase KDM6A have been found in cancer and are either positively or negatively associated with tumorigenesis and prognosis. However, the clinical relevance and functional role of KDM6A in lung cancer is largely unknown. We found that KDM6A protein expression was higher in NSCLC tissues than in the corresponding paracancer tissues and that high KDM6A expression was associated with poor patient prognosis. Furthermore, KDM6A knockdown in NSCLC cell lines markedly inhibited the tumorigenic phenotype both in vitro and in vivo. Mechanistically, KDM6A colocalized and cooperated with KMT2B to reprogram the transcriptional network via regulating the cancer pathway, in which abnormal activation of the Wnt pathway is the dominant factor. Interestingly, in NSCLC cell lines, H3K4me3 but not H3K27me2/3 or H3K4me1/2 was markedly altered upon KDM6A or KMT2B knockdown, indicating that KDM6A may act independently of H3K27 demethylases in NSCLC. Taken together, these results indicated that KDM6A or KMT2B may be a prognostic biomarker and promising therapeutic target in NSCLC.

Three-dimensional structured illumination microscopy (3D-SIM) plays an essential role in biological volumetric imaging with the capabilities of improving lateral and axial resolution. However, the traditional linear 3D algorithm is sensitive to noise and generates artifacts, while the low temporal resolution hinders live-cell imaging. In this paper, we propose a novel 3D-SIM algorithm based on total variation (TV) and fast iterative shrinkage threshold algorithm (FISTA), termed TV-FISTA-SIM. Compared to conventional algorithms, TV-FISTA-SIM achieves higher reconstruction fidelity with the least artifacts, even when the signal-to-noise ratio (SNR) is as low as 5 dB, and a faster reconstruction rate. Through simulation, we have verified that TV-FISTA-SIM can effectively reduce the amount of required data with less deterioration. Moreover, we demonstrate TV-FISTA-SIM for high-quality multi-color 3D super-resolution imaging, which can be potentially applied to live-cell imaging applications.

Three-dimensional structured illumination microscopy (3D-SIM) is an essential tool for volumetric fluorescence imaging, which improves both axial and lateral resolution by down-modulating high-frequency information of the sample into the passband of optical transfer function (OTF). And when combining with the 4Pi structure, the performance of 3D-SIM can be further improved. The reconstruction results of generally used linear 3D algorithm, however, are lack of high-fidelity and proneess to generate artifacts. In this paper, we proposed a novel iterative algorithm based on gradient descent combined with a nonlinear optimizer, which can be applied to all 3D-SIM setups (including I5S setup). We verified through simulation that the proposed solution, termed as nonlinear gradient descent structured illumination microscopy (NGD-SIM), achieves more fidelity results which can reach the limitation of theoretical resolution improvement of SIM. Moreover, it can be firmly validated on simulation that this algorithm can effectively reduce the amount of raw data in the case of sinusoidal-pattern illumination, i.e., the algorithm doesn’t need five-step phase shifting; data with any number of phases can theoretically be reconstructed. Our method also provides the possibility to extend the application of sinusoidal-pattern illumination to any kind of interference fringe, which is generated by diversified types of illumination mode.

Cross-modal interactions of auditory and visual temporal modulation were examined in a game-like experimental framework. Participants observed an audiovisual stimulus (an animated, sound-emitting fish) whose sound intensity and/or visual size oscillated sinusoidally at either 6 or 7 Hz. Participants made speeded judgments about the modulation rate in either the auditory or visual modality while doing their best to ignore information from the other modality. Modulation rate in the task-irrelevant modality matched the modulation rate in the task-relevant modality (congruent conditions), was at the other rate (incongruent conditions), or had no modulation (unmodulated conditions). Both performance accuracy and parameter estimates from drift-diffusion decision modeling indicated that (1) the presence of temporal modulation in both modalities, regardless of whether modulations were matched or mismatched in rate, resulted in audiovisual interactions; (2) congruence in audiovisual temporal modulation resulted in more reliable information processing; and (3) the effects of congruence appeared to be stronger when judging visual modulation rates (i.e., audition influencing vision), than when judging auditory modulation rates (i.e., vision influencing audition). The results demonstrate that audiovisual interactions from temporal modulations are bi-directional in nature, but with potential asymmetries in the size of the effect in each direction.

Dietary guidelines recommend removing visible fat from meat, choosing low-fat options and cooking with oil instead of butter. This study examined cross-sectional associations between fat-related eating behaviors and a continuous metabolic syndrome (cMetSyn) score among young adults. During 2004–2006, 2071 participants aged 26–36 years reported how often they trimmed fat from meat, consumed low-fat dairy products and used different types of fat for cooking. A fasting blood sample was collected. Blood pressure, weight and height were measured. To create the cMetSyn score, sex-specific principal component analysis was applied to normalized risk factors of the harmonized definition of metabolic syndrome. Higher score indicates higher risk. For each behavior, differences in mean cMetSyn score were calculated using linear regression adjusted for confounders. Analyses were stratified by weight status (Body mass index (BMI) &lt, 25 kg/m2 or ≥25 kg/m2). Mean cMetSyn score was positively associated with consumption of low-fat oily dressing (PTrend = 0.013) among participants who were healthy weight and frequency of using canola/sunflower oil for cooking (PTrend = 0.008) among participants who were overweight/obese. Trimming fat from meat, cooking with olive oil, cooking with butter, and consuming low-fat dairy products were not associated with cMetSyn score. Among young adults, following fat-related dietary recommendations tended to not be associated with metabolic risk.

When predicting where a target or reward will be, participants tend to choose each location commensurate with the true underlying probability (i.e., probability match). The strategy of probability matching involves independent sampling of high and low probability locations on separate trials. In contrast, models of probabilistic spatial attention hypothesize that on any given trial attention will either be weighted toward the high probability location or be distributed equally across all locations. Thus, the strategies of probabilistic sampling by choice decisions and spatial attention appear to differ with regard to low-probability events. This distinction is somewhat surprising because similar brain mechanisms (e.g., pFC-mediated cognitive control) are thought to be important in both functions. Thus, the goal of the current study was to examine the relationship between choice decisions and attentional selection within single trials to test for any strategic differences, then to determine whether that relationship is malleable to manipulations of catecholamine-modulated cognitive control with the drug modafinil. Our results demonstrate that spatial attention and choice decisions followed different strategies of probabilistic information selection on placebo, but that modafinil brought the pattern of spatial attention into alignment with that of predictive choices. Modafinil also produced earlier learning of the probability distribution. Together, these results suggest that enhancing cognitive control mechanisms (e.g., through prefrontal cortical function) leads spatial attention to follow choice decisions in selecting information according to rule-based expectations.

Boston's Museum of Science supports researchers whose projects advance science and provide educational opportunities to the Museum's visitors. For our project, 60 visitors to the Museum played “Fish Police!!,” a video game that examines audiovisual integration, including the ability to ignore irrelevant sensory information. Players, who ranged in age from 6 to 82 years, made speeded responses to computer-generated fish that swam rapidly across a tablet display. Responses were to be based solely on the rate (6 or 8 Hz) at which a fish's size modulated, sinusoidally growing and shrinking. Accompanying each fish was a task-irrelevant broadband sound, amplitude modulated at either 6 or 8 Hz. The rates of visual and auditory modulation were either Congruent (both 6 Hz or 8 Hz) or Incongruent (6 and 8 or 8 and 6 Hz). Despite being instructed to ignore the sound, players of all ages responded more accurately and faster when a fish's auditory and visual signatures were Congruent. In a controlled laboratory setting, a related task produced comparable results, demonstrating the robustness of the audiovisual interaction reported here. Some suggestions are made for conducting research in public settings.

RSA public-key cryptography and some other algorithms require various modular arithmetic operations. This paper presents an area efficient modular arithmetic processor. The operands can vary in size from 256 to 2048 bits. Optimized CIOS algorithm is introduced to speed up modular multiplication. At a maximum clock rate of 60 MHz, it takes 57 ms to complete a 1024-bit modular exponentiation. The core circuit without RAM contains 16000 gates and the whole area measures only 3.31 mm2 in a 0.35 mm CMOS technology. As a coprocessor, it is suitable for embedded systems, especially in area-constrained environments such as smart cards.

We used a specially designed computer game to examine behavioral consequences of audiovisual integration. Target stimuli (animated fish swimming across the computer screen) were modulated in size and/or emitted an amplitude-modulated sound. Modulations, visual or auditory, were at 6 or 7 Hz (corresponding to “slow” and “fast”). In one game, subjects were instructed to categorize successive fish as “slow” or “fast” based on the auditory modulations; in another game, they categorized fish based on visual modulation rate. In each game, subjects were instructed to ignore input from the task-irrelevant modality. In each game, modulations could be (1) present only in the modality of interest, (2) present and matching in both modalities, or (3) present but mismatched between modalities. While reaction times were similar across games, accuracy was highest when auditory modulation was the basis for categorizing fish. Accuracy and reaction times improved when cross-modal modulation rates matched, and worsened when modulation rates conflicted. Additionally, accuracy was more strongly affected by between-modality congruence/incongruence when subjects attended to visual modulations than when they attended to auditory ones. Results indicate that audiovisual integration is not entirely under volitional control, and that competition between sensory modalities adversely impacts perception in dynamic environments.