Miracle-dz/UniFAR-FTUs huggingface dataset:
A study of students’ learning perceptions and behaviors in remote STEM programming education

In recent years, STEM education has developed students’ fundamental subject knowledge, and has allowed students to integrate STEM cross-domain knowledge. Universities emphasize innovative thinking, practice and application, problem-solving, and teamwork to nurture students while learning STEM cross-domain knowledge development in remote STEM program education. When students take online STEM programs, they may encounter unanswered questions and may give up on trying to solve them. Therefore, this study proposed a problem-based learning approach with an online programming system integrated into an online STEM programming course. To help students solve the past programming assignments, the assignments were simplified, decomposed, and reorganized. The teacher guided the students to understand the STEM programming problems and taught them to use appropriate problem-solving skills to motivate them to complete the STEM programming assignments. The experiment was conducted with students in an online STEM programming course at a university in northern Taiwan. In the experimental activities, we used a problem-based learning approach for the online STEM programming activity. The problem-based learning method can be divided into four steps, namely stating the problem, understanding the problem, developing a solution plan, and executing the plan, reflecting, and debugging. This study used a problem-based learning approach and an online programming system integrated into a STEM programming curriculum to explore the differences in students’ perceptions of STEM learning, learning outcomes, and learning behaviors. The experimental results found a significant difference between students’ prior knowledge and learning outcomes. Students showed significant gains in learning the STEM programming content using the problem-based learning approach and the online programming system. In the analysis of their STEM learning perceptions, we found that there were significant differences in students’ responses for each dimension. This shows that using the problem-based learning approach with the online programming system helped students learn the course content. The analysis of students’ behaviors in answering the STEM programming assignments indicated that some students had the habit of taking notes. This helped them to easily associate and integrate STEM cross-domain knowledge with what they had learned in the online course, and enhanced their ability to implement STEM programs. In addition, students could take the initiative and focus on repeatedly watching the teacher solve the material in the online course. Students could try different solving plans to pass the code validation of the STEM programming assignments. This revealed that students wanted to complete the STEM programming assignments to achieve good learning performance.
The complex interactions between the cellular and non-cellular components of the brain tumor microenvironmental landscape and their therapeutic implications

Glioblastoma (GBM), an aggressive high-grade glial tumor, is resistant to therapy and has a poor prognosis due to its universal recurrence rate. GBM cells interact with the non-cellular components in the tumor microenvironment (TME), facilitating their rapid growth, evolution, and invasion into the normal brain. Herein we discuss the complexity of the interactions between the cellular and non-cellular components of the TME and advances in the field as a whole. While the stroma of non-central nervous system (CNS) tissues is abundant in fibrillary collagens, laminins, and fibronectin, the normal brain extracellular matrix (ECM) predominantly includes proteoglycans, glycoproteins, and glycosaminoglycans, with fibrillary components typically found only in association with the vasculature. However, recent studies have found that in GBMs, the microenvironment evolves into a more complex array of components, with upregulated collagen gene expression and aligned fibrillary ECM networks. The interactions of glioma cells with the ECM and the degradation of matrix barriers are crucial for both single-cell and collective invasion into neighboring brain tissue. ECM-regulated mechanisms also contribute to immune exclusion, resulting in a major challenge to immunotherapy delivery and efficacy. Glioma cells chemically and physically control the function of their environment, co-opting complex signaling networks for their own benefit, resulting in radio- and chemo-resistance, tumor recurrence, and cancer progression. Targeting these interactions is an attractive strategy for overcoming therapy resistance, and we will discuss recent advances in preclinical studies, current clinical trials, and potential future clinical applications. In this review, we also provide a comprehensive discussion of the complexities of the interconnected cellular and non-cellular components of the microenvironmental landscape of brain tumors to guide the development of safe and effective therapeutic strategies against brain cancer.
Multiple phytoplankton community responses to environmental change in a temperate coastal system: A trait-based approach

The effect of environmental change in structuring the phytoplankton communities of the coastal waters of the Eastern English Channel was investigated by applying a trait-based approach on two decades (1996-2019) of monitoring on diatoms and Phaeocystis. We show that phytoplankton species richness in an unbalanced nutrient supply context was influenced by wind-driven processes, ecological specialization for dissolved inorganic phosphorous, temporal niche differentiation, and a competition-defense and/or a growth-defense trade-off, a coexistence mechanism where weak competitors (i.e., slower growing) are better protected against predation. Under the influence of both environmental perturbations (e.g., wind-driven processes, freshwater influence, unbalanced nutrient levels) and biotic interactions (e.g., competition, predation, facilitation), phytoplankton species exhibited specific survival strategies such as investment on growth, adaptation and tolerance of species to environmental stresses, silicification and resource specialization. These strategies have led to more speciose communities, higher productivity, functional redundancy and stability in the last decade. Our results revealed that the unbalanced nutrient reduction facilitated Phaeocystis blooms and that anthropogenic climate warming and nitrate reduction may threaten the diatom communities of the eastern English Channel in a near future. Our results provide strong support for biogeographical historical and niche-based processes in structuring the phytoplankton community in this temperate region. The variety of species responses that we characterized in this region may help to better understand future changes in pelagic ecosystems, and can serve as a basis to consider functional approaches for future ecosystem management.
Structure‒function‒pathogenicity analysis of C-terminal myocilin missense variants based on experiments and 3D models

MYOC is a common pathogenic gene for primary open-angle glaucoma and encodes the protein named myocilin. Multiple MYOC variations have been found, with different clinical significance. However, the pathogenesis of glaucoma induced by MYOC mutations has not been fully clarified. Here, we analyze the molecular and cellular biological differences caused by multiple variant myocilins, including protein secretion characteristics, structural changes, subcellular localization, cellular autophagic activity and oxidative stress. Denaturing and nondenaturing electrophoresis showed myocilin to be a secreted protein with the tendency to self-oligomerize. The full-length myocilin and its C-terminal cleavage fragment are secreted. Secretion analysis of 23 variant myocilins indicated that secretion defects are closely related to the pathogenicity of MYOC variants. Structural analysis showed that the alteration of steric clash is associated with the secretion characteristics and pathogenicity of myocilin variants. Immunocytochemistry results demonstrated that mutated myocilins are retained in the endoplasmic reticulum and disrupt autophagy. MTT assay, MitoTracker staining, and DCFH-DA staining showed increased oxidative injury in cells expressing MYOC mutants. Taken together, MYOC mutations are able to induce cell dysfunction via secretion defects and intracellular accumulation resulting from steric clash alterations.
Acceptor dependent catalytic properties of GH57 4-α-glucanotransferase from Pyrococcus sp. ST04

The 4-α-glucanotransferase (4-α-GTase or amylomaltase) is an essential enzyme in maltodextrin metabolism. Generally, most bacterial 4-α-GTase is classified into glycoside hydrolase (GH) family 77. However, hyperthermophiles have unique 4-α-GTases belonging to GH family 57. These enzymes are the main amylolytic protein in hyperthermophiles, but their mode of action in maltooligosaccharide utilization is poorly understood. In the present study, we investigated the catalytic properties of 4-α-GTase from the hyperthermophile Pyrococcus sp. ST04 (PSGT) in the presence of maltooligosaccharides of various lengths. Unlike 4-α-GTases in GH family 77, GH family 57 PSGT produced maltotriose in the early stage of reaction and preferred maltose and maltotriose over glucose as the acceptor. The kinetic analysis showed that maltotriose had the lowest KM value, which increased amylose degradation activity by 18.3-fold. Structural models of PSGT based on molecular dynamic simulation revealed two aromatic amino acids interacting with the substrate at the +2 and +3 binding sites, and the mutational study demonstrated they play a critical role in maltotriose binding. These results clarify the mode of action in carbohydrate utilization and explain acceptor binding mechanism of GH57 family 4-α-GTases in hyperthermophilic archaea.
Quantitative phosphoproteomics analyses reveal the regulatory mechanisms related to frozen-thawed sperm capacitation and acrosome reaction in yak (Bos grunniens)

Mammalian spermatozoa are not mature after ejaculation and must undergo additional functional and structural changes within female reproductive tracts to achieve subsequent fertilization, including both capacitation and acrosome reaction (AR), which are dominated by post-translational modifications (PTMs), especially phosphorylation. However, the mechanism of protein phosphorylation during frozen-thawed sperm capacitation and AR has not been well studied. In this study, the phosphoproteomics approach was employed based on tandem mass tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) strategy to analyze frozen-thawed sperm in Ashidan yak under three sequential conditions (density gradient centrifugation-based purification, incubation in the capacitation medium and induction of AR processes by the calcium ionophore A23187 treatment). The identification of 1,377 proteins with 5,509 phosphorylation sites revealed changes in phosphorylation levels of sperm-specific proteins involved in regulation of spermatogenesis, sperm motility, energy metabolism, cilium movement, capacitation and AR. Some phosphorylated proteins, such as AKAP3, AKAP4, SPA17, PDMD11, CABYR, PRKAR1A, and PRKAR2A were found to regulate yak sperm capacitation and AR though the cAMP/PKA signaling pathway cascades. Notably, the phosphorylation level of SPA17 at Y156 increased in capacitated sperm, suggesting that it is also a novel functional protein besides AKAPs during sperm capacitation. Furthermore, the results of this study suggested that the phosphorylation of PRKAR1A and PRKAR2A, and the dephosphorylation of CABYR both play key regulatory role in yak sperm AR process. Protein-protein interaction analysis revealed that differentially phosphorylated proteins (AKAP3, AKAP4, FSIP2, PSMD11, CABYR, and TPPP2) related to capacitation and AR process played a key role in protein kinase A binding, sperm motility, reproductive process, cytoskeleton and sperm flagella function. Taken together, these data provide not only a solid foundation for further exploring phosphoproteome of sperm in yak, but an efficient way to identify sperm fertility-related marker phosphorylated proteins.
Performances statistiques d'algorithmes d'apprentissage : "Kernel projection machine" et analyse en composantes principales à noyau

La these se place dans le cadre de l'apprentissage statistique. Elle apporte des contributions a la communaute du machine learning en utilisant des techniques de statistiques modernes basees sur des avancees dans l'etude des processus empiriques. Dans une premiere partie, les proprietes statistiques de l'analyse en composantes principales a noyau (KPCA) sont explorees. Le comportement de l'erreur de reconstruction est etudie avec un point de vue non-asymptotique et des inegalites de concentration des valeurs propres de la matrice de Gram sont donnees. Tous ces resultats impliquent des vitesses de convergence rapides. Des proprietes non-asymptotiques concernant les espaces propres de la KPCA eux-memes sont egalement proposees. Dans une deuxieme partie, un nouvel algorithme de classification a ete concu : la Kernel Projection Machine (KPM). Tout en s'inspirant des Support Vector Machines (SVM), il met en lumiere que la selection d'un espace vectoriel par une methode de reduction de la dimension telle que la KPCA regularise convenablement. Le choix de l'espace vectoriel utilise par la KPM est guide par des etudes statistiques de selection de modele par minimisation penalisee de la perte empirique. Ce principe de regularisation est etroitement relie a la projection fini-dimensionnelle etudiee dans les travaux statistiques de Birge et Massart. Les performances de la KPM et de la SVM sont ensuite comparees sur differents jeux de donnees. Chaque theme aborde dans cette these souleve de nouvelles questions d'ordre theorique et pratique.
Advances in CAR T-cell therapy in bile duct, pancreatic, and gastric cancers

Bile duct, pancreatic, and gastric cancers are deadly digestive system tumors with high malignancy and poor patient prognosis. The efficiencies of conventional surgical treatment, radiation therapy, and chemotherapy are limited. In contrast, chimeric antigen receptor (CAR) T-cell therapy represents a landmark therapeutic approach to antitumor immunity with great efficacy in treating several hematological malignancies. CAR T-cell therapy involves genetically engineering the expression of specific antibodies based on the patient’s T-cell surface and amplifying these antibodies to identify and target tumor-associated antigens. CAR T-cell therapy can effectively inhibit disease progression and improve the survival of patients with bile duct, pancreatic, and gastric cancers. The effectiveness of CAR T cells in tumor therapy can be validated using xenograft models, providing a scientific testing platform. In this study, we have reviewed the progress in CAR T-cell production and its development, focusing on the current status and optimization strategies for engineered CAR T cells in the bile duct, pancreatic, and gastric cancers.
Intent disclosure in late-life suicide: Age group differences in correlates and associations with suicide means

Age-adjusted suicide rates declined from 2018 to 2020. However, suicide rates among older adults, particularly males 75 and older, have continued to rise, and the evidence base for effective interventions to prevent suicide in late life remains limited. One strategy to prevent older adults’ suicidal behavior is to intervene when they reveal suicide intent. Previous research found that a significant proportion of older suicide decedents disclosed their suicide intent close to the fatal incident. In this study, based on the 2017–2019 United States National Violent Death Reporting System (NVDRS) data, we examined: (1) correlates of intent disclosure among three age groups (65–74, 75–84, and 85+) of older suicide decedents (N = 17,917; 14,856 men and 3,061 women); and (2) associations of suicide means with intent disclosure and suicide contributing factors. The results show that 19.9% of all suicide decedents aged 65+ (18.7%, 21.0%, and 22.0% in the 65–74, 75–84, and 85+ age groups, respectively) disclosed their suicide intent to their partner, family/friends, and healthcare providers within a month of their death. Multivariable analyses using generalized linear models for a Poisson distribution with a log link showed that physical and mental health, substance misuse, addiction problems, and relationship/other life stressors were associated with a higher likelihood of intent disclosure in the 65–74 and 75–84 age groups. However, only physical health problems were associated with a higher likelihood of intent disclosure among those aged 85 and older. Intent disclosure was not associated with using firearms and poisoning as suicide means but with a lower likelihood of hanging or suffocation. Mental health and substance misuse problems were associated with higher odds of hanging or suffocation and poisoning, and physical health problems and male sex in the 85+ age group were associated with higher odds of firearm use. Suicide prevention strategies for those who have disclosed their suicide intent or are at risk of suicidal behavior should include more patient-centered comfort and palliative care, mental health/substance misuse/addiction treatment, and restriction of access to potential suicide means. More research on older adults who disclose suicide intent and late-life suicide prevention strategies is needed.
Effect of fruit intake on functional constipation: A systematic review and meta-analysis of randomized and crossover studies

Functional constipation (FC) is commonly treated with fruits whose efficacy remains unclear. We conducted a meta-analysis of fruit intervention for FC and provided evidence-based recommendations. We searched seven databases from inception to July 2022. All randomized and crossover studies on the effectiveness of fruits on FC were included. We conducted sensitivity and subgroup analysis. A total of 11 studies were included in this review. Four trials showed that kiwifruits have significantly increased stool frequency (MD = 0.26, 95% CI (0.22, 0.30), P < 0.0001, I2 = 0%) than palm date or orange juice in the fixed-effect meta-analysis. Three high-quality studies suggested that kiwifruits have a better effect than ficus carica paste on the symptom of the FC assessed by the Bristol stool scale in the fixed-effect meta-analysis [MD = 0.39, 95% CI (0.11, 0.66), P < 0.05, I2 = 27%]. Besides, five trials showed that fruits can increase the amount of Lactobacillus acidophilus [MD = 0.82, 95% CI (0.25, 1.39), P < 0.05, I2 = 52%], analyzed with the random-effect model. Subgroup meta-analysis based on the types of fruits suggested that fruits including pome fruit, citrus fruit, and berries have increased the effect of Bifidobacterium t more than the stone fruits in the random effect meta-analysis [MD = 0.51, 95% CI (0.23, 0.79), P < 0.05, I2 = 84%]. Totally, fruit intake may have potential symptom alleviation on the FC as evidence shows that they can affect stool consistency, stool frequency, and gut microbiota. Further large-scale studies are needed to gain more confident conclusions concerning the association between fruit intake and FC in the future.
18F-FDG distribution pattern improves the diagnostic accuracy of single pulmonary solid nodule

Background The main purpose is to explore the use of visual assessment of the heterogeneous distribution of 18F-FDG in single pulmonary solid lesions to differentiate the benign from the malignant. Methods The 200 cases of pulmonary nodules or masses examined by 18F-FDG PET/CT were retrospectively analyzed. The heterogeneity of 18F-FDG distribution of the lesion was visually and quantitatively evaluated and the higher part of metabolism was observed and measured at the proximal or distal part to determine the lesion nature. The sensitivity, specificity, PPV, NPV, and accuracy of this method were calculated. Results Total 171 pulmonary lesions showed heterogeneity of 18F-FDG uptake, including the 111 malignant and 60 benign. 54/60 (90.00%) benign lesions showed higher 18F-FDG uptake visually at distal part, while 104/111 (93.69%) malignant lesions showed higher 18F-FDG uptake visually at the proximal part. This visual method has good repeatability with a high kappa value (0.821, p<0.001). 52/60 (86.67%) benign lesions showed higher 18F-FDG uptake quantitatively at distal part, while 107/111 (96.40%) malignant lesions showed higher 18F-FDG uptake quantitatively at the proximal part. The sensitivity, specificity, PPV, NPV and accuracy of visual and quantitative methods were 93.69%; 96.40%, 90.0%; 86.67%, 94.55%; 93.04%, 88.52%; 92.86%, 92.40%; 92.98%, respectively (p<0.001). When combining the metabolic value and morphological characteristics of PET/CT with visual 18F-FDG heterogeneous features, the accuracy reached to 98.25%. The other 29 lesions (14.5%) with no heterogeneity were smaller (2.17 ± 1.06 vs 3.58 ± 1.48, P<0.001). Conclusions Benign and malignant lung lesions showed different heterogeneity of 18F-FDG uptake. Lung cancer can be effectively distinguished from infectious or inflammatory lesions by this simple and convenient method.
Immunogenic cell death as driver of autoimmunity in granulomatosis with polyangiitis

Cell death and dysregulated clearance of dead cells play essential roles in the induction of chronic inflammatory processes and autoimmune diseases. Granulomatosis with polyangiitis (GPA), a neutrophil-driven autoimmune disorder, is characterized by necrotizing inflammation predominantly of the respiratory tract and an anti-neutrophil cytoplasmic autoantibody (ANCA)-associated systemic necrotizing vasculitis. Defective regulation of neutrophil homeostasis and cell death mechanisms have been demonstrated in GPA. Disturbed efferocytosis (i.e., phagocytosis of apoptotic neutrophils by macrophages) as well as cell death-related release of damage-associated molecular patterns (DAMP) such as high mobility group box 1 (HMGB1) contribute to chronic non-resolving inflammation in GPA. DAMP have been shown to induce innate as well as adaptive cellular responses thereby creating a prerequisite for the development of pathogenic autoimmunity. In this review, we discuss factors contributing to as well as the impact of regulated cell death (RCD) accompanied by DAMP-release as early drivers of the granulomatous tissue inflammation and autoimmune responses in GPA.