It is widely approved that emotions play a critical role in language education. This inspires EFL teachers to establish a classroom oriented toward students' emotions and senses involved in the ...teaching/learning processes. Such an emotioncy-based pedagogy can bring about various positive outcomes in second/foreign language education. In tune with this, the present study briefly reviews the definitions, models, roots, and potentials of emotioncy in stopping student' boredom and pessimism. Moreover, it makes some references to empirical inquiries in this line of research to strengthen its scientific basis. Finally, the study presents a number of implications for teachers, teacher educators, and researchers in language education urging them to focus on students' emotions and senses more than before.
•We extracted urban heat island (UHI) clusters using an innovative approach.•We examined the nonlinear relationships between the LST and urban biophysical composition in UHI clusters.•The spatial ...heterogeneity of the landscape within UHI results in the complexity of LST.•Both NDVI and NDBI are great indicators for predicting the variations of LST in UHI clusters.
The spatio-temporal pattern of biophysical composition significantly affects land surface temperature (LST). Previous studies, however, mostly characterized urban heat island (UHI) clusters being spatially homogeneous. The landscape spatial heterogeneity in urban across UHI clusters challenges us to more accurately characterize the relationships between LST and corresponding urban biophysical composition. In this study, we introduced an innovative integrated approach that combined object-oriented image segmentation with local indicators of spatial autocorrelations (LISA) to extract UHI clusters from an LST image. We used a regression tree model to examine the nonlinear relationships between LST and each of three satellite-based indices within the UHI clusters: normalized differential vegetation index (NDVI), normalized differential build-up index (NDBI), and normalized difference bareness index (NDBaI). We found that both NDVI and NDBI are strongly correlated with the variations of LST whereas NDBaI has a weaker correlation with LST. We also found that the regression tree model built in this study enabled us to effectively detect the nonlinear relationship between LST and biophysical composition. Furthermore, based on a set of rules derived from a regression tree analysis, we found that urban landscapes strongly affect LST and its spatial heterogeneity within a UHI. These rules were used to detect the nonlinear impacts of complex urban biophysical composition on LST. The results of this study provided insights into how LST within UHI varies with urban surface characteristics at fine spatial scale and also a new method for investigating effects of land surface composition on LST in urbanized areas.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In contrast to the predominant chronic UV exposure-induced cutaneous melanoma in Caucasians, acral and mucosal comprise the majority of melanomas in Asia and respond less effectively to established ...treatments. The clinical application of PD-1 blockade is yet to be explored in metastatic melanoma in China.
This phase II study was to evaluate safety and efficacy of toripalimab in advanced Chinese patients with melanoma who had failed in systemic treatments. Toripalimab was given at 3 mg/kg i.v. once every 2 weeks until disease progression or unacceptable toxicity. The primary objective was safety and objective response rate.
128 Patients with melanoma were enrolled, including 50 acral and 22 mucosal. As of August 15, 2019, 23 months after the last enrollment, 116 (90.6%) experienced treatment-related adverse events. ≥Grade 3 TRAEs occurred in 25 (19.5%) patients. Among 127 patients assessed, 1 complete response, 21 partial response, and 51 stable disease were observed for objective response rate of 17.3% and disease control rate of 57.5%. Median duration of response was not reached. Median progression-free survival was 3.6 months 95% confidence interval (CI) 2.7-5.3 and median overall survival was 22.2 months (95% CI, 15.3-NE). Patients with positive PD-L1 staining in tumor biopsies had significant better ORR (38.5% vs. 11.9%,
= 0.0065), PFS (7.7 months vs. 2.7 months,
= 0.013), and OS (not reached vs. 14.4 months,
= 0.0005) than PD-L1-negative patients.
This is the largest prospective anti-PD-1 clinical study in advanced melanoma with predominantly acral and mucosal subtypes. Toripalimab demonstrated a manageable safety profile and durable clinical response in Chinese patients with metastatic melanoma refractory to standard therapy.
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BackgroundHepatitis B virus (HBV) reactivation is a serious complication in patients with cancers and HBV infection undergoing immunosuppressant treatment or chemotherapy. However, the safety of ...anti-programmed cell death (PD) -1 and anti-programmed cell death-ligand 1 (PD-L1) therapy in these patients is unknown because they were excluded from clinical trials of immunotherapy.MethodsThis retrospective cohort study involved consecutive hepatitis B surface antigen (HBsAg) -positive cancer patients who were referred to Sun Yat-sen University Cancer Center and received an anti-PD-1/PD-L1 antibody between January 1, 2015 and July 31, 2018. The primary end point was the rate of the occurrence of HBV reactivation.ResultsIn total, 114 eligible patients were included, among whom 90 (79%) were male, and the median (range) age was 46 (16–76) years. Six patients (5.3%) developed HBV reactivation, occurring at a median of 18 weeks (range, 3–35 weeks) from the commencement of immunotherapy. Among these patients, all of them had undetectable baseline HBV DNA; one had prophylactic antiviral therapy while five did not; four were positive for Hepatitis B e antigen while the other two were negative. At reactivation, the median HBV DNA level was 3.89 × 104 IU/mL (range, 1.80 × 103–6.00 × 107 IU/mL); five had HBV-related hepatitis and one exhibited increasing HBV DNA level without alanine transaminase elevation. No HBV-related fatal events occurred. The lack of antiviral prophylaxis was the only significant risk factor for HBV reactivation (odds ratio, 17.50 95% CI, 1.95–157.07, P = .004).ConclusionsHBV reactivation occurs in a subset of HBsAg-positive cancer patients undergoing anti-PD-1 or anti-PD-L1 immunotherapy. Regular monitoring of HBV DNA and antiviral prophylaxis are advised to prevent this potentially fatal complication.
Melanomas harbor aberrations in the c-Kit gene. We tested the efficiency of the tyrosine kinase inhibitor imatinib in selected patients with metastatic melanoma harboring c-Kit mutations or ...amplifications.
Forty-three patients with metastatic melanoma harboring c-Kit aberrations were enrolled on this phase II trial. Each patient received a continuous dose of imatinib 400 mg/d unless intolerable toxicities or disease progression occurred. Fifteen patients who experienced progression of disease were allowed to escalate the dose to 800 mg/d.
Forty-three patients were eligible for evaluation, and the median follow-up time was 12.0 months. The median progression-free survival (PFS) was 3.5 months, and the 6-month PFS rate was 36.6%. Rate of total disease control was 53.5%: 10 patients (23.3%; 95% CI, 10.2% to 36.4%) and 13 patients (30.2%; 95% CI, 16.0% to 44.4%) achieved partial response (PR) and stable disease (SD), respectively. Eighteen patients (41.9%) demonstrated regression of tumor mass. Notably, nine of the 10 PRs were observed in patients with mutations in exons 11 or 13. The 1-year overall survival (OS) rate was 51.0%. The median PFS and OS times for patients who had PR or SD versus disease progression were 9.0 months versus 1.5 months (P < .001) and 15.0 months versus 9.0 months (P = .036), respectively. Imatinib 400 mg/d was well tolerated, and only one of the 15 patients who received dose escalation to 800 mg/d achieved SD.
Imatinib demonstrated significant activity in patients with metastatic melanoma harboring genetic c-Kit aberrations, with an overall response rate of 23.3%. Escalation to 800 mg/d could not restore disease control.
Coherent diffractive imaging is unique, being the only route for achieving high spatial resolution in the extreme ultraviolet and X-ray regions, limited only by the wavelength of the light. Recently, ...advances in coherent short-wavelength light sources, coupled with progress in algorithm development, have significantly enhanced the power of X-ray imaging. However, so far, high-fidelity diffraction imaging of periodic objects has been a challenge because the scattered light is concentrated in isolated peaks. Here, we use tabletop 13.5 nm high-harmonic beams to make two significant advances. First, we demonstrate high-quality imaging of an extended, nearly periodic sample for the first time. Second, we achieve subwavelength spatial resolution (12.6 nm) imaging at short wavelengths, also for the first time. The key to both advances is a novel technique called 'modulus enforced probe', which enables robust and quantitative reconstructions of periodic objects. This work is important for imaging next-generation nano-engineered devices.
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IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UL, UM, UPUK
Programmed cell death ligand 1 (PD-L1) is an immune checkpoint protein frequently expressed in human cancers that contributes to immune evasion through its binding to PD-1 on activated T cells. ...Unveiling the mechanisms underlying PD-L1 expression is essential for understanding the impact of the immunosuppressive microenvironment and is also crucial for the purpose of reboosting antitumor immunity. However, how PD-L1 is regulated, particularly at translational levels, remains largely unknown. Here, we discovered that a long noncoding RNA (lncRNA), HIF-1α inhibitor at translation level (HITT), was transactivated by E2F transcription factor 1 (E2F1) under IFN-γ stimulation. It coordinated with regulator of G protein signaling 2 (RGS2) in binding to the 5' UTR of PD-L1, resulting in reduced PD-L1 translation. HITT expression enhanced T cell-mediated cytotoxicity both in vitro and in vivo in a PD-L1-dependent manner. The clinical correlation between HITT/PD-L1 and RGS2/PD-L1 expression was also detected in breast cancer tissues. Together, these findings demonstrate the role of HITT in antitumor T cell immunity, highlighting activation of HITT as a potential therapeutic strategy for enhancing cancer immunotherapy.
The current staging method is inadequate to identify high-risk recurrence patients with stage II colon cancer (CC). Using a systematic and comprehensive-biomarker discovery and validation method, we ...aimed to construct a lncRNA-based signature to improve the prognostic prediction of stage II CC. We identified 1,377 differently expressed lncRNAs by analyzing 16 paired stage II CC tumor tissue and adjacent normal mucosal tissue from the TCGA dataset. Subsequently, using a univariable and step multivariable Cox regression model, we trained an 11-lncRNA signature in the training cohort (n = 141), which could divide patients into high-risk and low-risk groups (AUC at 3 years = 0.801, 95% CI: 0.724-0.877; AUC at 5 years = 0.801, 95% CI: 0.718-0.885). Significantly, patients in the high-risk group had poorer recurrence-free survival (RFS) compared with the low-risk group (log-rank test, P < 0.001 in the training cohort). This lncRNA-based signature was further confirmed in the validation cohort (P < 0.001). Multivariate Cox regression and stratified survival analyses showed that the prognostic value of this signature was independent of other clinicopathological risk factors (CEA, T stage, and chemotherapy). Time-dependent receiver operating characteristic (ROC) analysis demonstrated that this signature had better prognostic ability than any other clinical risk factors or single lncRNAs (all P < 0.05). A nomogram was constructed for clinical use, which integrated both the lncRNA-based signature and clinical risk factors (CEA and T stage) and performed well in the calibration plots. Altogether, our lncRNA-based signature was an independent prognostic factor and possessed a stronger predictive power compared with the currently used clinicopathological risk factors when predicting the recurrence of patients with stage II CC. Collectively, this lncRNA-based signature might facilitate individualized treatment decisions and postoperative counseling, ultimately contributing to improved survival.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Limited studies have interrogated the genomic landscape of Chinese melanoma in which acral and mucosal melanoma are the mainstay. In this study, we carried out a retrospective analysis on 81 Chinese ...melanoma patients (15 acral, 25 mucosal and 41 cutaneous melanoma). With the identification of 1114 mutations spanning 248 genes, we summarized that the mutation spectrum varied significantly by subtypes. Acral melanoma and mucosal melanoma had significantly more CNVs. MYC amplification was one of the most commonly detected CNVs, other frequent CNVs in mucosal melanoma included NBN and KDR, which were associated with the poor survival of melanoma patients. A generally low TMB, with a median of only 5.1 mut/Mb, was observed in three groups including cutaneous melanoma. Additionally, over 50% variants in DNA damage repair pathway were detected in all three subtypes, most of which were HRD related genes. Patients with alterations of HRD related genes had a longer survival time after immunotherapy. This study revealed a molecular profiling of Chinese patients with advanced melanoma, and proposed the high variant rate in DDR pathway as a biomarker of immunotherapy, which might provide therapeutic targets and guidance in making clinical decision for different Chinese melanoma.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Pembrolizumab shows robust antitumor activity and favorable safety in metastatic melanoma. KEYNOTE-151 evaluated pembrolizumab in Chinese patients, who have more aggressive melanoma subtypes than ...other populations.
Chinese patients aged ≥18years with advanced melanoma previously treated with one line of therapy received pembrolizumab 2 mg/kg every 3 weeks for 35 cycles or until confirmed disease progression, intolerable toxicity, or study withdrawal. Primary end points were objective response rate (ORR) per RECIST v1.1 by blinded independent central review and safety. Key secondary end points included duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 and overall survival (OS).
Median age was 52 years (N=103); 37.9% had acral and 14.6% had mucosal melanoma. Median follow-up was 7.9months at data cutoff (December 27, 2017). ORR was 16.7% (95% CI, 10.0–25.3%) (1 complete, 16 partial responses). Disease control rate was 38.2%. ORR was 15.8% for acral, 13.3% for mucosal melanoma. Median DOR was 8.4months; 65.6% of patients had response duration ≥6months. Median PFS was 2.8months (95% CI, 2.7–3.5months); 6-month rate was 20.4%. Median OS was 12.1months (95% CI, 9.6months–not reached); 6-month rate, 75.7%; 12-month rate, 50.6%. Treatment-related AEs (TRAEs) occurred in 87 (84.5%) patients; 9 (8.7%) experienced grade 3/4 TRAE and 2 (1.9%) discontinued because of TRAE; none died. Two deaths occurred that were unrelated to treatment.
Pembrolizumab was well tolerated and provided clinically meaningful antitumor activity as second-line therapy in Chinese patients with advanced melanoma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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