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The purpose of this paper is to determine and discuss the factors that influence the learning outcomes of preservice teacher students in a blended learning environment. This quantitative study used a structured online questionnaire to collect responses from preservice teacher students (n=602) from five universities in Indonesia. Measurement analysis was used to validate the instrument, and the structural equation model was used to test the relationship between constructs. The model had four constructs: support system, learning strategy, digital literacy, and learning outcome. This study integrates three factors, namely support systems, learning strategies, and digital literacy, to identify the determinants of student-teacher learning outcomes in a blended learning environment. The research revealed that support systems and learning strategies have an effect on digital literacy and that digital literacy has a direct effect on learning outcomes. This research provides important insights regarding the contribution of support systems, learning strategies, and digital literacy to improve student learning outcomes in a blended learning environment.

This research aimed to examine the level of the implementation of authentic assessment by high school English teachers in a rural area of Siak district, Riau Province, Indonesia, and to explore their perception regarding authentic assessment. This research used a mixed method in which both quantitative and qualitative data were collected and analyzed. The research samples were 39 high school English teachers in the Siak region. The research instrument used is a questionnaire comprising 38 closed and three open questions, distributed online via Google Forms. The questionnaire was designed using Likert Scale with options ranging from 1-5 (very poor to very good) Data were also collected using semi-structured interviews to enrich data from the Google Form. This study found that the total average score of quantitative data is 4.1, classified as good. That means the implementation of authentic assessment by English teachers is at a good level. Then from the qualitative data analysis, it appeared that most teachers have a positive perception of authentic assessment as a tool for monitoring and evaluating student learning outcomes. However, there are still some problems faced by the teachers in implementing this assessment, such as the lack of time allotment for the English subject at school and the complexity of the assessment procedures. This implies that some policies are required to make the authentic assessment work well at school levels so teachers can benefit from the assessment for improving English learning at schools.

This study investigated student perceptions and preferences of Hybrid Flexible learning and equity. This research was conducted at fourteen universities with a research sample of 863 students. The cross-sectional survey design used online questionnaires and structured interviews for data collection. The collected data were then analyzed using the Jamovi program. The study examined students' positive perceptions of HyFlex learning modalities and equity. Students' positive perception of the face-to-face mode was the highest, followed by online asynchronous and synchronous modes. There was no gender relationship between face-to-face and equity modes, but there was a relationship between online synchronous and asynchronous modes. This study also found a positive perception of students toward equity, which explains the tendency of students to choose face-to-face and hybrid/blended modalities in the issue of equity or equity in HyFlex learning. This study also found that students' preferences for HyFlex learning modalities were mostly face-to-face and hybrid, followed by online synchronous and online asynchronous. This study also describes the qualitative reasons of students for choosing the HyFlex learning modality/mode.

All schools worldwide are rapidly entering the remote education process due to the COVID-19 outbreak. In this process, the math teacher becomes a remote math teaching partner. The teacher's experience in the remote teaching process of this mathematics subject, which is a compulsory subject in all senior secondary schools. This study aimed to see teachers' difficulties, such as problem-solving, class discussions, teaching aids, and appropriate learning methods. The participants of this study which was designed as a complex study were 15 experienced mathematics teachers in various schools in Banda Aceh. This research contributes to knowing the difficulties of mathematics teachers in teaching remotely to improve the quality of distance learning which the government is echoing in the present and future. The study results show that teachers have difficulties in remote math lessons. According to the findings of the research conducted by the participating teachers, mathematics classes should not be taught using applications for distance education; teachers have trouble interacting and communicating with students because there is limited interaction and a lack of direct feedback, and some students do not attend classes; there is a lack of information about the use of the internet and technological tools; there is a significant lack of sufficiency across the curriculum; there are some students who do not attend classes; there is a shortage of information about the use of technological tools.

BACKGROUND: Cutaneous melanoma (CM) can be molecularly classified into four groups: BRAF mutant, NRAS mutant, NF1 mutant and triple wild-type (TWT) tumors lacking any of these three alterations. In the era of immune checkpoint inhibition (ICI) and targeted molecular therapy, the clinical significance of these groups remains unclear. Here, we integrate targeted DNA sequencing with comprehensive clinical follow-up in CM patients. METHODS: This was a retrospective cohort study that assessed clinical and molecular features from patients with localized or metastatic CM who underwent targeted next-generation sequencing as part of routine clinical care. A total of 254 patients with CM who had a CLIA-certified targeted sequencing assay performed on their tumor tissue were included. RESULTS: Of the 254 patients with cutaneous melanoma, 77 were BRAF mutant (30.3%), 77 were NRAS mutant (30.3%), 47 were NF1 mutant (18.5%), 33 were TWT (13.0%) and the remaining 20 (7.9%) carried mutations in multiple driver genes (BRAF/NRAS/NF1 co-mutated). The majority of this co-mutation group carried mutations in NF1 (n = 19 or 90%) with co-occurring mutations in BRAF or NRAS, often with a weaker oncogenic variant. Consistently, NF1 mutant tumors harbored numerous significantly co-altered genes compared to BRAF or NRAS mutant tumors. The majority of TWT tumors (n = 29, 87.9%) harbor a pathogenic mutation within a known Ras/MAPK signaling pathway component. Of the 154 cases with available TMB data, the median TMB was 20 (range 0.7-266 mutations/Mb). A total of 14 cases (9.1%) were classified as having a low TMB (≤5 mutations/Mb), 64 of 154 (41.6%) had an intermediate TMB (>5 and ≤20 mutations/Mb), 40 of 154 (26.0%) had a high TMB (>20 and ≤50 mutations/Mb) and 36 of 154 (23.4%) were classified as having a very high TMB (>50 mutations/Mb). NRAS mutant melanoma demonstrated significantly decreased overall survival on multivariable analysis (HR for death 2.95, 95% CI 1.13-7.69, p = 0.027, log-rank test) compared with other TCGA molecular subgroups. Of the 116 patients in our cohort with available treatment data, 36 received a combination of dual ICI with anti-CTLA4 and anti-PD1 inhibition as first-line therapy. Elevated TMB was associated with significantly longer progression-free survival following dual-agent ICI (HR 0.26, 95% CI 0.07-0.90, p = 0.033, log-rank test). CONCLUSIONS: NRAS mutation in CMs correlated with significantly worse overall survival. Elevated TMB was associated with increased progression-free survival for patients treated with a combination of dual ICI, supporting the potential utility of TMB as a predictive biomarker for ICI response in melanoma.

BACKGROUND: Metastatic melanoma to the small bowel is an aggressive disease often accompanied by obstruction, abdominal pain, and gastrointestinal bleeding. With advancements in melanoma treatment, the role for metastasectomy continues to evolve. Inclusion of novel immunotherapeutic agents, such as checkpoint inhibitors, into standard treatment regimens presents potential survival benefits for patients receiving metastasectomy. CASE PRESENTATION: We report an institutional experience of 15 patients (12 male, 3 female) between 2014-2022 that underwent small bowel metastasectomy for metastatic melanoma and received perioperative systemic treatment. Median age of patients was 64 years (range: 35-83 years). No patients died within 30 days of their surgery, and the median hospital length of stay was 5 days. Median overall survival in these patients was 30.1 months (range: 2-115 months). Five patients died from disease (67 days, 252 days, 426 days, 572 days, 692 days postoperatively), one patient died of non-disease related causes (1312 days postoperatively), six patients are alive with disease, and three remain disease free. CONCLUSIONS: This case series presents an updated perspective of the utility of metastasectomy for small bowel metastasis in the age of novel immunotherapeutic agents as standard systemic treatment. Small bowel metastasectomy for advanced melanoma performed in conjunction with perioperative systemic therapy is safe and appears to promote long-term survival and enhanced quality of life.

Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using a discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified a nuclear-enriched lncRNA (AC004540.4) that is upregulated in NRAS/MAPK-dependent melanoma, and that we named T-RECS. Considering potential innovative treatment strategies, we designed antisense oligonucleotides (ASOs) to target T-RECS. T-RECS ASOs reduced the growth of melanoma cells and induced apoptotic cell death, while having minimal impact on normal primary melanocytes. Mechanistically, treatment with T-RECS ASOs downregulated the activity of pro-survival kinases and reduced the protein stability of hnRNPA2/B1, a pro-oncogenic regulator of MAPK signaling. Using patient- and cell line- derived tumor xenograft mouse models, we demonstrated that systemic treatment with T-RECS ASOs significantly suppressed the growth of melanoma tumors, with no noticeable toxicity. ASO-mediated T-RECS inhibition represents a promising RNA-targeting approach to improve the outcome of MAPK pathway-activated melanoma.

Purpose: This paper aims to investigate the effect of learning styles on HyFlex learning towards equity of learning in higher education. Design/methodology/approach: A quantitative approach was used, with data collection through a structured online questionnaire. The study participants were undergraduate students (n = 451) studying at various public and private universities in Indonesia. Measurement analysis is used to test the validity of the instrument used. Analysis of structural equations is used to test the relationships between the constructs under study. Findings: Survey instruments have satisfactory internal validity and consistency. The learning style of students in higher education positively influences the use of HyFlex's three learning modalities. All three modalities of HyFlex learning positively affect learning equity, especially the asynchronous online modality. However, the synchronous online effect is insignificant. Active/reflective learning styles only affect face-to-face mode but do not significantly affect the two online modalities, synchronous and asynchronous. Some of the learning style dimensions have an indirect effect on equity through three HyFlex learning modalities. Face-to-face and online asynchronous mediate well the indirect relationship between learning style and equity. The impact of gender and higher education status was not shown to strengthen the relationship between learning styles, HyFlex learning modalities and equity. Research limitations/implications: This study will provide valuable understanding for lecturers, educators and developers to adapt and develop HyFlex learning strategies based on the positive dimensions of the Felder-Silverman learning style that can support equitable and inclusive learning. The study forms a foundation for researchers to investigate more constructs that could improve HyFlex learning in future studies. Originality/value: This research is a pioneer in using learning styles to investigate trends in using three HyFlex learning modalities, particularly emphasising modalities that can provide equitable learning.

In this paper, a quick convergence adaptive structure is proposed for trajectory tracking of an articulated type robotic manipulator using the Hardware in the Loop (HIL) simulation technique. A novel Nonlinear Quick Convergence Adaptive Sliding Backstepping Control (QCASBC) algorithm is implemented on a C2000 real-time controller board. The performance of the proposed control algorithm is inspected concerning the sliding mode PID (SM-PID) control technique to estimate its correlation with the proposed algorithm. The experimental part of the HIL simulation tests has been carried out on a simulated model of a three-link serial robot manipulator. A dynamic model of the robotic manipulator has been developed using Matlab Simulink software and its performance is analyzed using the HIL technique via a C2000 real-time controller for tracking the desired trajectory. Results show that the speed of convergence while tracking the desired trajectory of the manipulator is better in the proposed algorithm. It is also estimated that the positional error of the QCASBC algorithm is superior to the SM-PID control algorithm. The observed average angle error is improved by 14% and the average response time error is improved by 11% by using the proposed QCASBC algorithm compared to the SM-PID approach.

Clustering is essential in data analysis, with K-means clustering being widely used for its simplicity and efficiency. However, several challenges can affect its performance, including the handling of outliers, the transformation of non-spherical data into a spherical form, and the selection of the optimal number of clusters. This paper addressed these challenges by developing and enhancing specific models. The primary objective was to improve the robustness and accuracy of K-means clustering in the presence of these issues. To handle outliers, this research employed the winsorization method, which uses threshold values to minimize the influence of extreme data points. For the transformation of non-spherical data into a spherical form, the KROMD method was introduced, which combines Manhattan distance with a Gaussian kernel. This approach ensured a more accurate representation of the data, facilitating better clustering performance. The third objective focused on enhancing the gap statistic for selecting the optimal number of clusters. This was achieved by standardizing the expected value of reference data using an exponential distribution, providing a more reliable criterion for determining the appropriate number of clusters. Experimental results demonstrated that the winsorization method effectively handles outliers, leading to improved clustering stability. The KROMD method significantly enhanced the accuracy of converting non-spherical data into spherical form, achieving an accuracy level of 0.83 percent and an execution time of 0.14 per second. Furthermore, the enhanced gap statistic method outperformed other techniques in selecting the optimal number of clusters, achieving an accuracy of 93.35 percent and an execution time of 0.1433 per second. These advancements collectively enhance the performance of K-means clustering, making it more robust and effective for complex data analysis tasks.