Search

Background: The complex tumor microenvironment of hepatocellular carcinoma (HCC) has led to a low response to immune checkpoints inhibitors (ICIs) and a poor prognosis. PD-L1, as one of the indications for ICIs, is rich in glycosylation modifications, which result in untimely ICIs. Our study constructed a prognostic model based on N-linked glycosylation related genes for predicting the prognosis and the response to ICIs. Methods: The patients in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts were enrolled. The Cox regression was performed to develop a prognostic model and patients were divided into a low-and high-risk subgroup. 21 recurrent HCC patients who received postoperative adjuvant ICIs were recruited and evaluated the response to ICIs. siRNA was used for in vitro validation. Results: 59 N-linked glycosylation related differentially expressed genes were screened from of HCC and normal tissues in the TCGA cohort. The prognostic model was developed with DDOST, STT3A and TMEM165. The risk score could be an independent prognostic factor. Patients in high-risk subgroup showed worse prognosis than patients in low-risk. ssGSEA showed that patients in the low-risk subgroup were more tend to be immune-activated state. Immunohistochemistry studies showed that DDOST, STT3A and TMEM165 are highly expressed in tumor tissues and patients with high risk score correlated with poor progression free survival and worse immunotherapeutic response. Knockdown of the three genes significantly reduce the proliferation of HCC cell lines. Conclusion: In this study, we establish that the risk model based on N-linked glycosylation related genes could efficiently predict the prognosis and tumor microenvironment immune state of HCC patients, and the risk score could serve as an indicator of ICIs.

This study aims to identify research trends of scaffolding in the field of science education. To this end, both descriptive analysis and co-word analysis were conducted to examine the selected articles published in the Social Science Citation Index journals from 2000 to 2019. A total of 637 papers were retrieved as research samples through rounds of searching in Web of Science database. Overall, this study reveals a growing trend of science educators' academic publications about scaffolding in the recent two decades. In these sample papers, from 1,487 non-repeated keywords, we extracted 286 author-defined keywords shared by at least two studies as a benchmark dictionary. A series of co-word analyses were then conducted based on the dictionary to reveal the underlying co-occurring relationships of the words in title and abstract of the sample papers. Results showed that “scaffolding,” “support,” and “design” were the top three most frequently used keywords during 2000 and 2019. Visualization of co-word networks in each 5-year period further helps clarify both educators' common research foci and relevant research trends. Derived discussion and potential research directions are also provided.

This article proposes a theoretical framework for conceptualizing socioscientific decision making, reviews current research in this area, and intends to shed some light on the instructional design for the classroom implementation of socioscientific decision making. The framework involves 3 phases: formulate the decision-making space, posit a decision-making strategy, and reflect on the decision-making process. A total of 24 articles that specifically focused on socioscientific decision making were included. They were classified into 2 groups. The first group explored students’ socioscientific decision-making behavior and its relationships with their cognitive conditions. The second examined the effectiveness of the interventions, that is, task conditions. The analysis showed that most of the studies in both groups focused on phase 1 and studied 3 research themes: informal reasoning, evidence-based reasoning, and social interactions. The findings indicated the challenges phases 1 and 2 posed to students, such as prioritizing criteria and employing a suitable decision-making strategy. Two cognitive conditions, scientific knowledge and scientific epistemological beliefs, appeared to have a more direct impact on evidence-based reasoning rather than on informal reasoning. Group 2 studies designed various interventions and looked into divergent socioscientific decision-making performances across 3 phases. The framework helps conceptualize socioscientific decision making in a more structural and holistic way. The content review provides instructional insights for the socioscientific decision-making process and suggests several future research directions.

This study aimed at improving the decision-making (DM) skills of 11th graders by incorporating a DM framework, visualisation tools, collaboration, and metacognitive guidance into a socioscientific issue context. Two classes, the experimental group (embedded metacognitive guidance, N = 42) and the comparison group (no metacognitive guidance, N = 32), were involved in the implementation of the experimental methodology. An open-ended test and worksheets were developed to assess the students’ DM skills. The results indicated that the two versions of the DM learning modules had similar effects on the improvement in the students’ DM skills, but there were significant differences in their overall skills in DM (Z = −6.410, p

Endoglin (CD105) is a type-1 integral transmembrane glycoprotein and coreceptor for transforming growth factor-β (TGF-β) ligands. The endoglin/TGF-β signaling pathway regulates hemostasis, cell proliferation/migration, extracellular matrix (ECM) synthesis and angiogenesis. Angiogenesis contributes to early progression, invasion, postoperative recurrence, and metastasis in hepatocellular carcinoma (HCC), one of the most widespread malignancies globally. Endoglin is overexpressed in newly formed HCC microvessels. It increases microvessel density in cirrhotic and regenerative HCC nodules. In addition, circulating endoglin is present in HCC patients, suggesting potential for use as a diagnostic or prognostic factor. HCC angiogenesis is dynamic and endoglin expression varies by stage. TRC105 (carotuximab) is an antibody against endoglin, and three of its clinical trials were related to liver diseases. A partial response was achieved when combining TRC105 with sorafenib. Although antiangiogenic therapy still carries some risks, combination therapy with endoglin inhibitors or other targeted therapies holds promise.

During mammalian embryonic development, primary cilia transduce and regulate several signaling pathways. Among the various pathways, Sonic hedgehog (SHH) is one of the most significant. SHH signaling remains quiescent in adult mammalian tissues. However, in multiple adult tissues, it becomes active during differentiation, proliferation, and maintenance. Moreover, aberrant activation of SHH signaling occurs in cancers of the skin, brain, liver, gallbladder, pancreas, stomach, colon, breast, lung, prostate, and hematological malignancies. Recent studies have shown that the tumor microenvironment or stroma could affect tumor development and metastasis. One hypothesis has been proposed, claiming that the pancreatic epithelia secretes SHH that is essential in establishing and regulating the pancreatic tumor microenvironment in promoting cancer progression. The SHH signaling pathway is also activated in the cancer stem cells (CSC) of several neoplasms. The self-renewal of CSC is regulated by the SHH/Smoothened receptor (SMO)/Glioma-associated oncogene homolog I (GLI) signaling pathway. Combined use of SHH signaling inhibitors and chemotherapy/radiation therapy/immunotherapy is therefore key in targeting CSCs.

The purpose of this investigation was to examine, from a cross-cultural perspective, students' epistemological patterns of reasoning about socioscientific issues (SSI), and to identify potential interactions of cultural and scientific identity. Mediating factors associated with students' argumentation and discourse about SSI, as well as the public's understanding of science, has been identified as an important area of investigation in the field of science education. This mixed-methods design included over 300 students from Jamaica, South Africa, Sweden, Taiwan, and the United States. Students responded to instruments designed to assess their epistemological conceptualizations and justifications related to distributive justice, allocation of scarce medical resources, and epistemological beliefs over five dimensions related to scientific knowledge. Four iterations of a coding scheme produced over 97% inter-rater agreement for four independent coders. Results indicate there is a consistent trend toward epistemological congruity across cultures within inductively derived themes of: (1) Fairness; (2) Pragmatism; (3) Emotive Reasoning; (4) Utility; and (5) Theological Issues. Moreover, there were no discernable differences in terms of how students from these countries presented their beliefs on the sub-categories of each of the five major categories. It appears that students displayed a high degree of congruence with respect to how they frame their reasoning on this SSI as well as their justifications for their epistemological beliefs. There were statistically significant differences regarding the ability to raise scientifically relevant questions among countries. Commonalities as well as distinguishing characteristics in epistemological orientations are compared and contrasted and connections to a model of socioscientific reasoning with implications for research and pedagogy are discussed. © 2013 Wiley Periodicals, Inc. J Res Sci Teach 50:251–283, 2013

This content analysis of articles in the Social Science Citation Index journals from 1995 to 2009 was conducted to provide science educators with empirical evidence regarding the effects of scaffolding on science learning. It clarifies the definition, design, and implementation of scaffolding in science classrooms and research studies. The results show important cross-study evidence that most researchers have adopted a qualitative approach (67.44%), focused on learning context (72.09%), and used high school students as participants (53.49%). In designing scaffoldings, researchers have shown a preference for long-term explicit scaffolding using multiple representations to promote procedural and strategic skills and alternative assessments of learner performance. Nevertheless, scaffolding issues related to teacher education are unexpectedly few (11.63%) in empirical research. The results also indicate that there are too few studies to guide researchers in considering fading scaffolds for active learning (9.30%). Future directions and suggestions toward conducting research regarding scaffolding are provided.

This article describes an effort to explore and enhance argumentation skills of Taiwanese grade 6 students through instruction in socioscientific issues. An experienced elementary school teacher was given 8 months of personalized instruction on argumentation skills and socioscientific issues, then subsequently implemented a 17-h classroom unit on the establishment of Ma-Guo National Park. His students learned to establish claims and warrants, construct counterarguments, offer supportive arguments, and provide evidence for each one. Data consisted of student responses to questionnaires and individual follow-up interviews. A multiple regression analysis revealed that success in learning argumentation skills was not substantially related to pre-instruction argumentation skills, but significantly related to the student ability levels. High-ability students were significantly better than low-ability students at generating complete arguments. Most students elaborated their arguments, and more high-ability students offered rebuttals after instruction. However, even these high achievers did not completely understand the meaning of evidence and often misused supplementary warrants as evidence.

A scientifically literate person should be able to engage and critique science news reports about socioscientific issues from a variety of information sources. Such engagement involves critical thinking and argumentation skills to determine if claims made are justified by evidence and explained by reasonable explanations. This study explored university students’ critical thinking performance when they read science news reports. Undergraduate science/applied science (n = 52) and non-science (n = 52) majors were asked to select a science news report from Internet sources and then to read, critique, and make comments about its contents. The science and non-science majors’ comments and their quality were identified and assessed in terms of analyzing the argument elements—claims and warrants, counterclaims and warrants, rebuttals, qualifiers, and evidence. The results indicated there is significant difference in identifying and formulating evidence favoring science/applied science over non-science majors (p

A major reason for infertility is due to male factors, including the quality of spermatozoa, which is a primary factor and often difficult to assess, particularly the total sperm concentration and its motile percentage. This work presents a simple microfluidic device to assess sperm quality by quantifying both total and motile sperm counts. The key design feature of the microfluidic device is two channels separated by a permeative phase-guide structure, where one channel is filled with raw semen and the other with pure buffer. The semen sample was allowed to reach equilibrium in both chambers, whereas non-motile sperms remained in the original channel, and roughly half of the motile sperms would swim across the phase-guide barrier into the buffer channel. Sperms in each channel agglomerated into pellets after centrifugation, with the corresponding area representing total and motile sperm concentrations. Total sperm concentration up to 10(8) sperms per ml and motile percentage in the range of 10-70% were tested, encompassing the cutoff value of 40% stated by World Health Organization standards. Results from patient samples show compact and robust pellets after centrifugation. Comparison of total sperm concentration between the microfluidic device and the Makler chamber reveal they agree within 5% and show strong correlation, with a coefficient of determination of R(2) = 0.97. Motile sperm count between the microfluidic device and the Makler chamber agrees within 5%, with a coefficient of determination of R(2) = 0.84. Comparison of results from the Makler Chamber, sperm quality analyzer, and the microfluidic device revealed that results from the microfluidic device agree well with the Makler chamber. The sperm microfluidic chip analyzes both total and motile sperm concentrations in one spin, is accurate and easy to use, and should enable sperm quality analysis with ease.