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This study was done to evaluate the diagnostic accuracy of cerebrospinal fluid kappa free light chain (KFLC) for diagnosis of multiple sclerosis, against isoelectrofocusing (IEF) to detect oligoclonal bands (OCB) as gold standard. 64 cases were divided into positive and negative based on the OCB results. Diagnostic accuracy was calculated for the 1 mg/L cut-off. The 1 mg/L cut-off yielded a percent agreement of 86.1% and Cohen’s kappa value of 0.8. Youden’s index, yielded a cut-off of 0.92 mg/L as optimal (90.3% specificity and 90.9% sensitivity). The analytical time was 3 hours and 55 min for IEF and 25 min for KFLC. The cost of a single OCB test was PKR12 000 (US$68.17) compared with PKR4150 (US$23.58) for KFLC. KFLC proved to be an accurate, cheaper and time-saving alternative and can be performed prior to the contemporary testing.

Sleep disturbance is usually present in night-shift workers. The objective of this study was to explore the relationships among fatigue, general health, coping and sleep disturbance together with mediating role of general health and moderating role of coping strategies i.e. Task, Emotion oriented &Avoidance in night-shift call center workers. Correlation research design was adopted with sample (N=200) assessed from call centers of Lahore by applying purposive sampling strategy. Data was obtained by administering Multi-dimensional Fatigue Inventory, General Health Questionnaire-28, Coping Inventory for Stressful Situations-21, and Screening Questionnaire for Sleep Disturbance in Shift Workers. Data was analyzed by using Pearson product moment correlation, Hierarchical Multiple Regression Analysis and Hayes Process Regression analysis. Results of this study state that fatigue correlated positively with general health and sleep disturbance. General health, task-oriented, emotion-oriented and avoidance coping strategies also have positive relationship with sleep disturbance. General health seems to have full mediation effect on the relationship of fatigue and sleep disturbance. Task and emotion-oriented coping strategies appear as a moderator while avoidance coping strategy does not appear as a moderator between the relationship of fatigue and sleep disturbance. This research has future implications for identifying night shift call centers workers having proneness to develop Shift work disorder due to sleep disturbance and provides them with better sleep hygiene guidelines to protect their health.

Cells orchestrate histone biogenesis with strict temporal and quantitative control. To efficiently regulate histone biogenesis, the repetitiveDrosophila melanogasterreplication-dependent histone genes are arrayed and clustered at a single locus. Regulatory factors concentrate in a nuclear body known as the histone locus body (HLB), which forms around the locus. Historically, HLB factors are largely discovered by chance, and few are known to interact directly with DNA. It is therefore unclear how the histone genes are specifically targeted for unique and coordinated regulation. To expand the list of known HLB factors, we performed a candidate-based screen by mapping 30 publicly available ChIP datasets and 27 factors to theDrosophilahistone gene array. We identified novel transcription factor candidates, including theDrosophilaHox proteins Ultrabithorax, Abdominal-A and Abdominal-B, suggesting a new pathway for these factors in influencing body plan morphogenesis. Additionally, we identified six other transcription factors that target the histone gene array: JIL-1, Hr78, the long isoform of fs(1)h as well as the generalized transcription factors TAF-1, TFIIB, and TFIIF. Our foundational screen provides several candidates for future studies into factors that may influence histone biogenesis. Further, our study emphasizes the powerful reservoir of publicly available datasets, which can be mined as a primary screening technique.

Scientific reasoning competencies (SRC) are one part of science teachers’ professional competencies. This study examines the contribution of three factors to the development of pre-service science teachers’ SRC: the amount of science education classes, the amount of science classes and the pre-service science teachers’ age. The factors amount of science education classes and amount of science classes have been operationalised in terms of ECTS credit points. N = 438 pre-service science teachers from six universities in Germany, Chile and Canada voluntarily and anonymously responded to an established multiple-choice instrument for assessing SRC, which has been developed by the authors and is available in German, Spanish and English. Multiple linear regression analyses show that the included factors explain a proportion of about 9% of the pre-service science teachers’ SRC. The factor amount of science classes is the only significant predictor and can be seen as an indicator of learning science content knowledge. These findings support the assumption of science content knowledge being a prerequisite for developing pre-service science teachers’ SRC.

We examine the effect of an innovation in an educational context, a class of 500 + first-year economics students at a well-known Australian university. We study whether introducing content in the form of a multimedia presentation has a detectable effect on specific categories of student knowledge. The multimedia presentation has a narrator presenting concepts with images, words, and worked examples. Our key outcome measure is the probability of answering questions correctly on a mid-term test. A quasi-experimental design is followed to offer a causal interpretation of the results. We find that the multimedia presentation markedly increases students' academic outcomes on the test compared to those that did not view the presentation, especially in regards to procedural and evaluative knowledge. An additional survey reveals gains in students' metacognitive knowledge. These findings suggest that multimedia presentations contribute to improved student learning outcomes and offer valuable options at a time of increased online course delivery. The findings also highlight the relevance of investing in education and resources to develop the necessary design skills among academics and staff.The online version of this article contains supplementary material available 10.1007/s11423-022-10147-3.

Globally, Cancer is believed to be second biggest reason of mortality and one of the significant social as well as economic liabilities. Despite our advance at molecular level in comprehension of cancer, more therapeutic tools and tactics are needed to exploit this advance. The CRISPER/Cas9 genome modifying approach has lately appeared as an effective cancer therapy method due to its high accuracy and efficiency. CRISPER/Cas9 has enormous clinical potential in discovering new targets for cancer treatment and also to dismember genetic-chemical interaction thus helping us to understand the response of tumor to the treatment by drugs. Additionally, Cas9/CRISPER can also be used in cancer immunotherapeutic applications by engineering immune cells and oncolytic viruses. Perhaps the most important therapeutic application of Cas9/CRISPER is its ability to edit genes with great precision both in animal models and humans. In this review, we will debate and explore some important concerns of using CRISPER/Cas9 in remedial settings and some vital hurdles that are needed to overcome before it is used for a clinical trial for a polygenic and complex ailment like cancer.

BACKGROUND AND AIMS Complete loss of histone H3 lysine 27 trimethylation (H3K27me3) has recently emerged as a biomarker for malignant peripheral nerve sheath tumours (MPNST). Loss of H3K27me3 staining has also been reported in post-radiation MPNST; however, it has not been evaluated in a large series of radiation-associated sarcomas of different histological subtypes. The aim of this study was to assess H3K27me3 labelling by immunohistochemistry in radiation-associated sarcomas and to determine the prevalence of H3K27me3 loss in these tumours. METHODS AND RESULTS Radiation-associated sarcomas (n = 119) from two tertiary care referral centres were evaluated for loss of H3K27me3, defined as complete loss of staining within tumour cells in the presence of a positive internal control. Twenty-three cases (19%) showed H3K27me3 loss, including nine of 10 (90%) MPNST, seven of 77 (9%) undifferentiated spindle cell/pleomorphic sarcomas, five of 25 (20%) angiosarcomas, one of five (20%) leiomyosarcomas and one of two (50%) osteosarcomas. CONCLUSIONS Complete H3K27me3 loss was present in 19% of radiation-associated sarcomas in our series. Our findings demonstrate that loss of H3K27me3 is not specific for radiation-associated MPNST and may also occur in other histological subtypes of RAS, including radiation-associated undifferentiated spindle cell/pleomorphic sarcoma, angiosarcoma, leiomyosarcoma and osteosarcoma.

In this study, we analysed the scientific reasoning competencies of preservice science teachers from a Canadian sample at the beginning and end of a science teacher education methods course. The course contained standard topics, such as the nature of science, assessment, and unit and lesson planning in science. The preservice science teachers were asked to reason about two types of problems in a validated pre- and post-questionnaire: investigatory-process problems and problems regarding modeling. Statistical analysis of the data revealed that the course significantly contributed to the development of preservice science teachers’ competencies for those who had two previous degrees compared with those that did not. Furthermore, a greater proportion of teachers were deemed highly competent at planning investigations and testing models than the more generative dimensions of scientific reasoning, such as formulating questions and generating hypotheses. Implications for science teacher education internationally and the movement towards competency-based curricula are put forward.

BACKGROUND AND OBJECTIVES: Well-differentiated liposarcomas (WDL) are often partly composed of sclerotic tissue, however, the amount varies widely between tumors, and its prognostic significance is unknown. We hypothesized that tumors with more sclerosis would behave more aggressively. METHODS: Primary retroperitoneal WDL from 29 patients resected at our institution with follow-up were histologically evaluated by soft tissue pathologists blinded to outcome. Tumors with ≥ 10% sclerosis were designated “sclerotic” while tumors with < 10% sclerosis were designated as “minimally sclerotic”. Cellular and dedifferentiated tumors were excluded. Clinical parameters and radiologic assessments on computed tomography (CT) were recorded. RESULTS: Histological evaluation identified 13 minimally sclerotic WDL and 16 sclerotic WDL. Median follow-up was 9 years (range, 3–20). Median recurrence-free survival (RFS) and median overall survival (OS) were 6.16 and 13.9 years, respectively. Compared with patients with sclerotic WDL, those with minimally sclerotic WDL had superior RFS (HR = 0.17 [95% CI, 0.06–0.53], P = .002) and OS (log-rank test, P = .002). Sclerotic WDL exhibited higher Houndsfield Units than minimally sclerotic WDL (26 vs 1, P = .040). CONCLUSIONS: Minimally sclerotic WDL were associated with more favorable outcome compared with sclerotic tumors. Assessment of sclerosis in WDL is likely a useful prognostic marker.

The development and evaluation of valid assessments of scientific reasoning are an integral part of research in science education. In the present study, we used the linear logistic test model (LLTM) to analyze how item features related to text complexity and the presence of visual representations influence the overall item difficulty of an established, multiple-choice, scientific reasoning competencies assessment instrument. This study used data from n = 243 pre-service science teachers from Australia, Canada, and the UK. The findings revealed that text complexity and the presence of visual representations increased item difficulty and, in total, contributed to 32% of the variance in item difficulty. These findings suggest that the multiple-choice items contain the following cognitive demands: encoding, processing, and combining of textually presented information from different parts of the items and encoding, processing, and combining information that is presented in both the text and images. The present study adds to our knowledge of which cognitive demands are imposed upon by multiple-choice assessment instruments and whether these demands are relevant for the construct under investigation—in this case, scientific reasoning competencies. The findings are discussed and related to the relevant science education literature.

The “Adopt a Bacterium” project is based on the use of social network as a tool in Microbiology undergraduate education, improving student learning and encouraging students to participate in collaborative learning. The approach involves active participation of both students and teachers, emphasizing knowledge exchange, based on widely used social media. Students were organized in groups and asked to adopt a specific bacterial genus and, subsequently, submit posts about “adopted genus”. The formative assessment is based on posting information on Facebook®, and the summative assessment involves presentation of seminars about the adopted theme. To evaluate the project, students filled out three anonymous and voluntary surveys. Most of the students enjoyed the activities and positively evaluated the experience. A large amount of students declared a change in their attitude towards the way they processed information, especially regarding the use of scientific sources. Finally, we evaluated knowledge retention six months after the end of the course and students were able to recall relevant Microbiology concepts. Our results suggest that the “Adopt a Bacterium” project represents a useful strategy in Microbiology learning and may be applied to other academic fields.

The majority of terrestrial plants associate with fungi in symbiotic resource-exchange relationships called mycorrhizae. Because of the importance of these mycorrhizal systems to ecosystem functioning, it is crucial that future resource managers and scientists have a solid understanding of mycorrhizal ecology. Limited interest of postsecondary students in plants and fungi compared with animals, combined with difficulties visualizing below-ground processes, present challenges for learning mycorrhizal concepts. To address this, we created the digital, plant-ecology-centric, action-based game Shroomroot for use in a second year, postsecondary Introduction to Soil Science course. We then assessed effects of Shroomroot on students’ knowledge acquisition and engagement with the topic of mycorrhizal ecology using a pre- and post-test evaluation. Students’ knowledge of mycorrhizal ecology increased significantly after playing Shroomroot, and tended to increase more for items related to Shroomroot gameplay than in rewards-based game content. Student engagement with mycorrhizal content tended to increase after gameplay. These results suggest positive potential for action-based, plant-ecology-oriented digital games in a postsecondary science curriculum. Furthermore, greater understanding of mycorrhizae has the potential to improve our multifaceted relationships with the ecosystems upon which we depend.

AIMS Multiple genetic alterations, including alternative lengthening of telomeres (ALT) and NOTCH mutations, have been described in angiosarcoma. Loss of α-thalassaemia/mental retardation syndrome X-linked (ATRX) and death domain-associated protein 6 (DAXX) expression is frequently associated with the ALT phenotype. Additionally, inhibition of NOTCH signalling induces the development of malignant vascular tumours in mice, indicating a tumour suppressive role of the NOTCH pathway in the pathogenesis of angiosarcoma. The aim of this study was to evaluate the immunohistochemical expression of ATRX, DAXX and NOTCH receptors (NOTCH1 and NOTCH2) in a large cohort of angiosarcomas, and study their clinicopathological and prognostic significance. METHODS AND RESULTS One hundred and forty cases of angiosarcoma were stained for ATRX, DAXX, NOTCH1 and NOTCH2. ATRX loss (

SUMMARY The dynamic evolution of chromatin state patterns during metastasis, their relationship with bona fide genetic drivers, and their therapeutic vulnerabilities are not completely understood. Combinatorial chromatin state profiling of 46 melanoma samples reveals an association of NRAS mutants with bivalent histone H3 lysine 27 trimethylation (H3K27me3) and Polycomb repressive complex 2. Reprogramming of bivalent domains during metastasis occurs on master transcription factors of a mesenchymal phenotype, including ZEB1, TWIST1, and CDH1. Resolution of bivalency using pharmacological inhibition of EZH2 decreases invasive capacity of melanoma cells and markedly reduces tumor burden in vivo, specifically in NRAS mutants. Coincident with bivalent reprogramming, the increased expression of pro-metastatic and melanocyte-specific cell-identity genes is associated with exceptionally wide H3K4me3 domains, suggesting a role for this epigenetic element. Overall, we demonstrate that reprogramming of bivalent and broad domains represents key epigenetic alterations in metastatic melanoma and that EZH2 plus MEK inhibition may provide a promising therapeutic strategy for NRAS mutant melanoma patients., Graphical abstract, In brief Terranova et al. provide a comprehensive epigenome resource for melanoma encompassing 284 chromatin maps. They find key regulatory roles for bivalent and broad domains in expression of pro-metastatic genes and identify EZH2 plus MEK inhibition as a therapeutic strategy for NRAS mutant melanomas.

Patient- and stakeholder-oriented research is vital to improving the relevance of research. The authors aimed to identify the 10 most important research priorities of patients, caregivers, and healthcare providers (family physicians, nurses, nurse practitioners, pharmacists, and dietitians) for hypertension management. Using the James Lind Alliance approach, a national web-based survey asked patients, caregivers, and care providers to submit their unanswered questions on hypertension management. Questions already answered from randomized controlled trial evidence were removed. A priority setting process of patient, caregiver, and healthcare providers then ranked the final top 10 research priorities in an in-person meeting. There were 386 respondents who submitted 598 questions after exclusions. Of the respondents, 78% were patients or caregivers, 29% lived in rural areas, 78% were aged 50 to 80 years, and 75% were women. The 598 questions were distilled to 42 unique questions and from this list, the top 10 research questions prioritized included determining the combinations of healthy lifestyle modifications to reduce the need for antihypertensive medications, stress management interventions, evaluating treatment strategies based on out-of-office blood pressure compared with conventional (office) blood pressure, education tools and technologies to improve patient motivation and health behavior change, management strategies for ethnic groups, evaluating natural and alternative treatments, and the optimal role of different healthcare providers and caregivers in supporting patients with hypertension. These priorities can be used to guide clinicians, researchers, and funding bodies on areas that are a high priority for hypertension management research for patients, caregivers, and healthcare providers. This also highlights priority areas for improved knowledge translation and delivering patient-centered care.

In this study, the author investigated how four science teachers employed model-based teaching (MBT) over a 1-year period. The purpose of the research was to develop a baseline of the fundamental and specific dimensions of MBT that are present and absent in science teaching. Teacher interviews, classroom observations, and pre and post-student assessments were gathered. Using a Generate-Evaluate-Modify framework as a theoretical guide, the author identified three fundamental aspects of MBT that were not apparent in an analysis of the teaching methods. Drawing on these findings, the author hypothesizes the consequent impact of the absence of these aspects on MBT on students’ experiences and performance in science. Implications for core science teacher professional development activities on MBT are discussed.

Teaching science with computer simulations is a complex undertaking. This case study examines how an experienced science teacher taught chemistry using computer simulations and the impact of his teaching on his students. Classroom observations over 3 semesters, teacher interviews, and student surveys were collected. The data was analyzed for (1) patterns in teacher-student-computer interactions, and (2) the outcome of these interactions on student learning. Using Technological Pedagogical Content Knowledge (TPCK) as a theoretical framework, analysis of the data indicates that computer simulations were employed in a unique instructional cycle across 11 topics in the science curriculum and that several teacher-developed heuristics were important to guiding the pedagogical approach. The teacher followed a pattern of “generate-evaluate-modify” (GEM) to teach chemistry, and simulation technology (T) was integrated in every stage of GEM (or T-GEM). Analysis of the student survey suggested that engagement with T-GEM enhanced conceptual understanding of chemistry. The author postulates the affordances of computer simulations and suggests T-GEM and its heuristics as an effective and viable pedagogy for teaching science with technology.

The Seventh School Curriculum Reform in Korea was introduced in 2000 to prepare school‐aged Koreans for an information and knowledge‐based society. The reform effort emphasises information and communication technology (ICT) in the K–12 curriculum and a learner‐centred pedagogy. This study examines the contributions of ICT, specifically, computer‐assisted instruction (CAI), in Korean science classrooms. A sample of 234 Korean middle school students was categorised into five achievement groups. Data were collected from pre‐ and post‐achievement test scores and pre‐ and post‐questionnaires for attitudes toward science, future courses, and career aspirations in science. Findings include: (1) the lowest achievement group showed the most significant improvement after CAI (p=.000); (2) an improvement in student achievement in science significantly influenced students’ attitudes toward science (p=.019), future course selections, and career aspirations related to science (p=.000); and (3) boys tended to perform be...

This paper uses a cultural model approach to interpret and analyse the impact of an interactive computer simulation tool (GB-Quest) on the possibility of fostering dialogue about sustainability in southwestern British Columbia, Canada. We define cultural models theory, compare cultural models to mental models and illustrate some basic features of cultural models. We then describe the research process in which participants engaged in conversation, guided and facilitated by GB-Quest, about sustainability. Findings suggest that the use of cultural models frameworks reinforces participants' understanding of sustainability. In reflecting on their prior models of sustainability, we argue that study participants can elucidate how cognitive conceptual resources reflect publicly shared knowledge (Turner, 2004).

This research assessed the value of case study methodology in the design of an educational computer simulation. Three sources of knowledge were compared to assess the value of case study: practitioner and programmer knowledge, disciplinary knowledge, and knowledge obtained from a case study of teacher practice. A retrospective analysis revealed that the case study was the source of 16 out of 23 design decisions and therefore was the most significant influence on the design of the simulation. The case study was particularly effective in sensitizing the design team to the classroom context, identifying common and uncommon teacher practices, revealing unexpected dimensions of interactions in the classroom, and generating constructive changes to the design of the simulation. Case studies can significantly enrich the design of educational software and are a promising methodological choice for design teams.

In this paper, instructional strategies for sustaining model-based inquiry in an undergraduate chemistry class were analyzed through data collected from classroom observations, a student survey, and in-depth problem-solving sessions with the instructor and students. Analysis of teacher–student interactions revealed a cyclical pattern in which students generated, evaluated, and modified (GEM) hypotheses throughout the course. It is hypothesized that sustained involvement in the GEM cycle contributed to students' engagement with scientific inquiry and model construction and revision. As such, GEM represents a promising approach toward achieving process and content goals in the undergraduate chemistry classroom. © 2007 Wiley Periodicals, Inc. Sci Ed, 91:877–905, 2007

This article reports on the value of using student‐generated analogies with undergraduate science students as a strategy for promoting conceptual understanding. A quantitative study was undertaken involving students in four sections of an introductory chemistry course for prospective science majors attending a four year college in British Columbia, Canada. Students in one section of the course developed, performed and discussed analogies representing a conceptually difficult chemistry topic. Students in three other sections received instruction on the same topic via a teacher‐generated analogy combined with in‐class discussion. To assess the impact of student‐generated analogies, students’ performance on a final exam question was compared across the four sections and their answers were analyzed for evidence of depth of conceptual understanding. Students who generated their own analogies performed significantly better in the exam and demonstrated a greater level of conceptual understanding than students wh...