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This research presents an investigation on the utilization of Science, Technology, Engineering, and Mathematics (STEM) with Project-Based Learning as experiment class treatment and project-based learning as control class treatment to investigate students' critical thinking in optical instruments lessons, with a particular focus on the development of handmade projectors. In Indonesian schools, where there is a lack of integration of the STEM and learning activity itself, it is still in the form of a direct transfer of knowledge from teachers to students. This research used quantitative research with a quasi-experimental design. The method for data collection is purposive random sampling. The research participant consists of 60 eighth-grade middle high school students in Bandung chosen based on a purposive random sampling technique. The data is obtained through five open-ended essay questions about critical thinking skills. The result shows that the independent t-test for students' critical thinking is 0.081, which means there are no significant differences between the control and experiment classes. However, in the STEM Project-based learning model, The N-gain of students' critical thinking skills is 0.718, which is a high improvement. Moreover, on Project-Based Learning, the N-gain of students' critical thinking skills is 0.660, which is a medium improvement.

Hydrogen can be used to reduce the concentration of reactive oxygen species (ROS), but its delivery to diseased tissues is challenging due to its low solubility. Here the authors develop a photosynthesis-inspired FRET nanocomplex to detect and scavenge local excess of ROS in the tissue using photocatalytic hydrogen production.

Students' problem-solving strategies and the differences among strategy groups were explored by analyzing the process data collected during student interactions with computer-based science items. Data were gathered from 1516 eleventh-grade students from 4 schools in China. Analyses of the sequences of students' response actions revealed that the students were divided into four strategy groups when designing experiments to solve scientific problems: the scientific and rigorous strategy (18.5%), scientific and less rigorous strategy (25.4%), incomplete strategy (31.5%), and chaotic strategy (24.6%). The heatmaps of response actions for each strategy and the frequencies of the most representative response sequences were further explored to understand the students' detailed trajectories. The results showed that successful problem solvers were generally inclined to explore all possibilities of experimental combinations and design experiments scientifically and rigorously based on the relevant scientific principles. Moreover, the timestamps of response actions were explored to show that the students who adopted the scientific and rigorous strategy spent more time seeking solutions, suggesting that students may need sufficient time to solve complex and authentic scientific problems. The findings enrich the literature on using process data to address theoretical issues in educational assessment and provide students with individualized instructional needs for teachers to improve students' scientific problem-solving competency.

Abstract Homologous recombination during meiosis is critical for chromosome segregation and also gives rise to genetic diversity. Genetic exchange between homologous chromosomes during meiosis is mediated by the recombinase Dmc1, which is capable of recombining DNA sequences with mismatches. The Hop2-Mnd1 complex mediates Dmc1 activity. Here, we reveal a regulatory role for Hop2-Mnd1 in restricting substrate selection. Specifically, Hop2-Mnd1 upregulates Dmc1 activity with DNA substrates that are either fully homologous or contain DNA mismatches, and it also acts against DNA strand exchange between substrates solely harboring microhomology. By isolating and examining salient Hop2-Mnd1 separation-of-function variants, we show that suppressing illegitimate DNA recombination requires the Dmc1 filament interaction attributable to Hop2-Mnd1 but not its DNA binding activity. Our study provides mechanistic insights into how Hop2-Mnd1 helps maintain meiotic recombination fidelity.

This study examined the effects of a technology-enhanced intervention on the self-regulation of 262 eighth-grade students, employing information and communication technology (ICT) and web-based self-assessment tools set against science learning. The data were analyzed using Bayesian structural equation modeling to unravel the intricate relationships between self-regulation, self-efficacy, perceptions of ICT, and self-assessment tools. Our research findings underscored the direct and indirect impacts of self-efficacy, perceived ease of use, and perceived use of technology on self-regulation. The results revealed the predictive power of self-assessment tools in determining self-regulation outcomes, underlining the potential of technology-enhanced self-regulated learning environments. The study posited the necessity to transcend mere technology incorporation and to emphasize the inclusion of monitoring strategies explicitly designed to augment self-regulation. Interestingly, self-efficacy appeared to indirectly influence self-regulation outcomes through perceived the use of technology rather than direct influence. Analytically, this research indicated that Bayesian estimation could offer a more comprehensive insight into structural equation modeling by assessing the estimates' uncertainty. This research substantially contributes to comprehending the influence of technology-enhanced environments on students' self-regulated learning, stressing the importance of constructing practical tools explicitly designed to cultivate self-regulation.

In this study, we aimed to characterize students' inquiry skill profiles and investigate whether students' gender, major, school location and type, and household registration are related to their inquiry skill profiles. By providing an animation-based activity, we engaged students in a scientific inquiry on the atmospheric chemistry of climate change. Students performed data analytics, control of variables, and scientific reasoning tasks, which represented essential skills in the inquiry process. After removing the invalid data and conducting the two-stage stratified sampling, we analyzed 724 11th-grade Chinese students' multiple-choice and open-ended responses. A latent profile analysis (LPA) was used to identify if there were subgroups of students' inquiry skills. ?2 tests were conducted to examine whether the profiles' distribution differed in gender, major, school location, school type, and household registration. We identified four types of inquiry skill profiles among students: sophisticated, experimental, moderate, and basic, based on their skills in data analytics, scientific reasoning, and control of variables. The findings showed that school location significantly affected students' inquiry profiles, while school type, student major, and hukou had a mildly favorable impact. To sum up, the marriage of the LPA approach and the animation-based activity has illuminated not just students' different inquiry skill profiles but also the relationships these profiles have with certain demographic factors. We discussed that it is imperative to recognize these varied inquiry skill profiles and work to bridge the disparities stemming from demographic differences for a more equitable science education environment.

Background: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). Methods: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-μg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1–3 months. Results: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-μg mRNA-1273, 467 (32.8%) 50-μg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count 200 copies/mL (aOR, 0.27; 95% CI, 0.09–0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68–5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10–0.41; reference, 100-μg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). Conclusions: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-μg mRNA-1273 could generate a higher antibody response than with 50-μg mRNA-1273 and BNT162b2 vaccine.

Abstract To unravel fault zone properties, high-resolution imaging and probing are pivotal. Here we present a comprehensive study utilizing Distributed Dynamic Strain Sensing of a 3D array of optical fiber with a surface-to-depth installation, traversing an active fault zone at depth, combined with a geological analysis of drilled cores. We identify an asymmetric fault zone with a narrow fault core, exhibiting a notable amplification in strain rate across a broad-band frequency range, which is attributed to the presence of weak gouge material within a much stronger host rock. This feature heightens responsiveness of the weak fault zone with low rigidity to ground motion, and intensifies strain from both nearby and remote seismic events. We demonstrate that optical fiber facilitates long-term monitoring of ground motion amplification with high spatial resolution, thus indicating where strain and deformation accumulate through repeating ruptures. This progress is pivotal to the understanding of the role of low rigidity and changes thereof within fault gouge material.

Background/Objectives: Relapsed B-cell acute lymphoblastic leukemia (B-ALL) remains an unresolved matter of concern regarding adverse outcomes. This case study aimed to evaluate the effectiveness of blinatumomab, with or without door lymphocyte infusion (DLI), in treating measurable residual disease (MRD)-positive B-ALL. Methods: All patients who received blinatumomab salvage therapy were included in this study. Eleven patients were included in the study. All patients were evaluated for MRD-negativity. Results: Before starting blinatumomab therapy, seven patients tested positive for MRD, three tested negative, and one had refractory disease. Hematopoietic cell transplantation (HCT) was reserved for five patients with persistent MRD. Six patients became MRD-negative and subsequent HCT was not performed. Only two patients relapsed; one patient died of relapse, and the other one received carfilzomib-based therapy and was MRD-negative thereafter. Nine patients were MRD-negative at a median follow-up of 28 months (15–52 months). Two of three MRD-positive post-transplant patients remained in complete molecular remission after preemptive DLI at the last follow-up date. In the first salvage, blinatumomab may achieve complete remission and bridging to HCT in pediatric patients with end-of-induction MRD-positive B-cell precursor ALL. Conclusions: The decision on how to treat post-transplant relapse continues to affect survival outcomes. Blinatumomab combined with DLI may extend the armamentarium of release options for high-risk pediatric patients. This approach is encouraging for high-risk ALL patients who are MRD-positive post-transplantation.

Abstract The classical Cauchy surface area formula states that the surface area of the boundary ∂ K = Σ $\partial K=\Sigma $ of any n-dimensional convex body in the n-dimensional Euclidean space R n $\mathbb{R}^{n}$ can be obtained by the average of the projected areas of Σ along all directions in S n − 1 $\mathbb{S}^{n-1}$ . In this note, we generalize the formula to the boundary of arbitrary n-dimensional submanifold in R n $\mathbb{R}^{n}$ by introducing a natural notion of projected areas along any direction in S n − 1 $\mathbb{S}^{n-1}$ . This surface area formula derived from the new notion coincides with not only the result of the Crofton formula but also with that of De Jong (Math. Semesterber. 60(1):81–83, 2013) by using a tubular neighborhood. We also define the projected r-volumes of Σ onto any r-dimensional subspaces and obtain a recursive formula for mean projected r-volumes of Σ.

BackgroundThe endonasal endoscopic approach (EEA) is effective for pituitary adenoma resection. However, manual review of operative videos is time-consuming. The application of a computer vision (CV) algorithm could potentially reduce the time required for operative video review and facilitate the training of surgeons to overcome the learning curve of EEA. ObjectiveThis study aimed to evaluate the performance of a CV-based video analysis system, based on OpenCV algorithm, to detect surgical interruptions and analyze surgical fluency in EEA. The accuracy of the CV-based video analysis was investigated, and the time required for operative video review using CV-based analysis was compared to that of manual review. MethodsThe dominant color of each frame in the EEA video was determined using OpenCV. We developed an algorithm to identify events of surgical interruption if the alterations in the dominant color pixels reached certain thresholds. The thresholds were determined by training the current algorithm using EEA videos. The accuracy of the CV analysis was determined by manual review, and the time spent was reported. ResultsA total of 46 EEA operative videos were analyzed, with 93.6%, 95.1%, and 93.3% accuracies in the training, test 1, and test 2 data sets, respectively. Compared with manual review, CV-based analysis reduced the time required for operative video review by 86% (manual review: 166.8 and CV analysis: 22.6 minutes; P

Abstract Background Cancer susceptibility germline mutations are associated with pancreatic ductal adenocarcinoma (PDAC). However, the hereditary status of PDAC and its impact on survival is largely unknown in the Asian population. Methods Exome sequencing was performed on 527 blood samples from PDAC individuals and analyzed for mutations in 80 oncogenic genes. Pathogenic and likely pathogenic (P/LP) germline variants were diagnosed according to the ACMG variant classification categories. The association between germline homologous recombination gene mutations (gHR mut , including BAP1, BRCA1, BRCA2, PALB2, ATM, BLM, BRIP1, CHEK2, NBN, MUTYH, FANCA and FANCC) and the treatment outcomes was explored in patients with stage III/IV diseases treated with first-line (1L) platinum-based versus platinum-free chemotherapy. Results Overall, 104 of 527 (19.7%) patients carried germline P/LP variants. The most common mutated genes were BRCA2 (3.60%), followed by ATR (2.66%) and ATM (1.9%). After a median follow-up duration of 38.3-months (95% confidence interval, 95% CI 35.0–43.7), the median overall survival (OS) was not significantly different among patients with gHR mut , non-HR germline mutations, or no mutation (P = 0.43). Among the 320 patients with stage III/IV disease who received 1L combination chemotherapy, 32 (10%) had gHR mut . Of them, patients receiving 1L platinum-based chemotherapy exhibited a significantly longer median OS compared to those with platinum-free chemotherapy, 26.1 months (95% CI 12.7–33.7) versus 9.6 months (95% CI 5.9–17.6), P = 0.001. However, the median OS of patients without gHR mut was 14.5 months (95% CI 13.2–16.9) and 12.6 months (95% CI 10.8–14.7) for patients receiving 1L platinum-based and platinum-free chemotherapy, respectively (P = 0.22). These results were consistent after adjusting for potential confounding factors including age, tumor stage, performance status, and baseline CA 19.9 in the multivariate Cox regression analysis. Conclusions Our study showed that nearly 20% of Taiwanese PDAC patients carried germline P/LP variants. The longer survival observed in gHR mut patients treated with 1L platinum-based chemotherapy highlights the importance of germline testing for all patients with advanced PDAC at diagnosis.

From June 2022 to April 2023, 1629 HIV-positive participants were assessed for the risk of atherosclerotic cardiovascular disease (ASCVD). The 10-year ASCVD risk of

Abstract Background CDGSH iron-sulfur domain-containing protein 2 (CISD2), a pro-longevity gene, mediates healthspan in mammals. CISD2 is down-regulated during aging. Furthermore, a persistently high level of CISD2 promotes longevity and ameliorates an age-related skin phenotype in transgenic mice. Here we translate the genetic evidence into a pharmaceutical application using a potent CISD2 activator, hesperetin, which enhances CISD2 expression in HEK001 human keratinocytes from an older person. We also treated naturally aged mice in order to study the activator’s anti-aging efficacy. Methods We studied the biological effects of hesperetin on aging skin using, firstly, a cell-based platform, namely a HEK001 human keratinocyte cell line established from an older person. Secondly, we used a mouse model, namely old mice at 21-month old. In the latter case, we investigate the anti-aging efficacy of hesperetin on ultraviolet B (UVB)-induced photoaging and naturally aged skin. Furthermore, to identify the underlying mechanisms and potential biological pathways involved in this process we carried out transcriptomic analysis. Finally, CISD2 knockdown HEK001 keratinocytes and Cisd2 knockout mice were used to study the Cisd2-dependent effects of hesperetin on skin aging. Results Four findings are pinpointed. Firstly, in human skin, CISD2 is mainly expressed in proliferating keratinocytes from the epidermal basal layer and, furthermore, CISD2 is down-regulated in the sun-exposed epidermis. Secondly, in HEK001 human keratinocytes from an older person, hesperetin enhances mitochondrial function and protects against reactive oxygen species-induced oxidative stress via increased CISD2 expression; this enhancement is CISD2-dependent. Additionally, hesperetin alleviates UVB-induced damage and suppresses matrix metalloproteinase-1 expression, the latter being a major indicator of UVB-induced damage in keratinocytes. Thirdly, transcriptomic analysis revealed that hesperetin modulates a panel of differentially expressed genes that are associated with mitochondrial function, redox homeostasis, keratinocyte function, and inflammation in order to attenuate senescence. Intriguingly, hesperetin activates two known longevity-associated regulators, namely FOXO3a and FOXM1, in order to suppress the senescence-associated secretory phenotype. Finally, in mouse skin, hesperetin enhances CISD2 expression to ameliorate UVB-induced photoaging and this occurs via a mechanism involving CISD2. Most strikingly, late-life treatment with hesperetin started at 21-month old and lasting for 5 months, is able to retard skin aging and rejuvenate naturally aged skin in mice. Conclusions Our results reveal that a pharmacological elevation of CISD2 expression at a late-life stage using hesperetin treatment is a feasible approach to effectively mitigating both intrinsic and extrinsic skin aging and that hesperetin could act as a functional food or as a skincare product for fighting skin aging.

Orbital cellulitis and severe preseptal cellulitis are critical periocular infections with potential vision- and life-threatening implications. The COVID-19 pandemic is hypothesized to have had an influence on their presentation and pathogenesis; however, the real impact remains unclear. In this retrospective multicenter cohort study from January 2017 to December 2022, we analyzed 1285 cases with preseptal or orbital cellulitis in pre-pandemic (2017–2019) and pandemic (2020–2022) cohorts. A notable decrease in hospitalized cases during the pandemic period was observed (97 patients in the pre-pandemic group vs. 54 in the pandemic group, p = 0.004), particularly among individuals aged 30–39 (p = 0.028). Sinusitis remained the leading cause, but odontogenic cases increased (p = 0.025). In addition, microbial diversity decreased during the pandemic, with the effective number of species decreasing from 17.07 to 8.87, accompanied by a rise in antibiotic resistance, notably against erythromycin, oxacillin, penicillin, and metronidazole. While visual outcomes appeared worse in the pandemic group, statistical significance was not reached. These findings suggest that the characteristics, etiology, microbial profiles, resistance patterns, and visual outcomes of orbital and preseptal cellulitis have undergone alterations post-COVID-19 pandemic. Vigilance in clinical management and public health measures is crucial, with further research needed to optimize treatment strategies.

The most commonly occurring cancer in the world is breast cancer with more than 500,000 cases across the world. The detection mechanism for breast cancer is endoscopist-dependent and necessitates a skilled pathologist. However, in recent years many computer-aided diagnoses (CADs) have been used to diagnose and classify breast cancer using traditional RGB images that analyze the images only in three-color channels. Nevertheless, hyperspectral imaging (HSI) is a pioneering non-destructive testing (NDT) image-processing technique that can overcome the disadvantages of traditional image processing which analyzes the images in a wide-spectrum band. Eight studies were selected for systematic diagnostic test accuracy (DTA) analysis based on the results of the Quadas-2 tool. Each of these studies’ techniques is categorized according to the ethnicity of the data, the methodology employed, the wavelength that was used, the type of cancer diagnosed, and the year of publication. A Deeks’ funnel chart, forest charts, and accuracy plots were created. The results were statistically insignificant, and there was no heterogeneity among these studies. The methods and wavelength bands that were used with HSI technology to detect breast cancer provided high sensitivity, specificity, and accuracy. The meta-analysis of eight studies on breast cancer diagnosis using HSI methods reported average sensitivity, specificity, and accuracy of 78%, 89%, and 87%, respectively. The highest sensitivity and accuracy were achieved with SVM (95%), while CNN methods were the most commonly used but had lower sensitivity (65.43%). Statistical analyses, including meta-regression and Deeks’ funnel plots, showed no heterogeneity among the studies and highlighted the evolving performance of HSI techniques, especially after 2019.

The involvement of stress ethylene in early chilling injury (CI) symptom development of mature-green (MG) banana fruit was examined using the ethylene action inhibitor, 1-methyclopropene (1-MCP). MG banana fruit pretreated with 0 or 50 μg L−1 1-MCP were stored at two chilling temperatures, 5 °C or 10 °C, for 0, 1, 12, or 72 h (different CI stresses), then transferred to 20 °C (rewarming) for 2 d. Irreversible CI symptoms that developed during 72 h storage at 5 or 10 °C included vascular browning and epidermal color parameters (L*, chroma, and hue angle). Some CI symptoms drastically intensified during exposure to 5 or 10 °C for 72 h, even being exacerbated after rewarming. Fruit in the other treatments suffered milder CI, and the recovery response progressed from slight and reversible to severe and irreversible with longer durations of exposure to lower temperatures. The effect of 1-MCP pretreatment was to attenuate the effect of chilling in terms of the CI symptom development (i.e., the browning of sub-epidermal tissues and the increasing of electrolyte efflux) and to promote recovery after rewarming, especially for the fruit stored at 5 °C, indicating the potential involvement of ethylene in membrane structural alterations under CI stress.