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Breast cancer incidence and mortality rates have increased exponentially during the last decade, particularly among female patients. Current therapies, including surgery and chemotherapy, have significant negative physical and mental impacts on patients. As a safer alternative, gene therapy utilising a therapeutic gene with the potential to treat various ailments is being considered. Delivery of the gene generally utilises viral vectors. However, immunological reactions and even mortality have been recorded as side effects. As a result, non-viral vectors, such as liposomes, a system composed of lipid bilayers formed into nanoparticles, are being studied. Liposomes have demonstrated tremendous potential due to their limitless ability to combine many functions into a system with desirable characteristics and functionality. This article discusses cationic, anionic, and neutral liposomes with their stability, cytotoxicity, transfection ability, cellular uptake, and limitation as a gene carrier suitable for gene therapy specifically for cancer. Due to the more practical approach of employing electrostatic contact with the negatively charged nucleic acid and the cell membrane for absorption purposes, cationic liposomes appear to be more suited for formulation for gene delivery and therapy for breast cancer treatment. As the other alternatives have numerous complicated additional modifications, attachments need to be made to achieve a functional gene therapy system for breast cancer treatment, which were also discussed in this review. This review aimed to increase understanding and build a viable breast cancer gene therapy treatment strategy.

To assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates. Systematic review and meta-analysis of head-to-head randomized trials of statin and fibrate monotherapy. MEDLINE, EMBASE, Cochrane, WHO International Controlled Trials Registry Platform, and ClinicalTrials.gov were searched through October 30, 2019. Trials that had a follow-up of at least 28 days, and reported mortality or a cardiovascular outcome of interest were eligible for inclusion. Efficacy outcomes were cardiovascular mortality and major cardiovascular events. Safety outcomes included myalgia, serious adverse effects, elevated serum creatinine, and elevated serum alanine aminotransferase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the Mantel-Haenszel fixed-effect model, and heterogeneity was assessed using the I2 statistic. We included 19 eligible trials that directly compared statin and fibrate monotherapy and reported mortality or a cardiovascular event. Studies had a limited duration of follow-up (range 10 weeks to 2 years). We did not find any evidence of a difference between statins and fibrates for cardiovascular mortality (OR 2.35, 95% CI 0.94-5.86, I2 = 0%; ten studies, n = 2657; low certainty), major cardiovascular events (OR 1.15, 95% CI 0.80-1.65, I2 = 13%; 19 studies, n = 7619; low certainty), and myalgia (OR 1.32, 95% CI 0.95-1.83, I2 = 0%; ten studies, n = 6090; low certainty). Statins had less serious adverse effects (OR 0.57, 95% CI 0.36-0.91, I2 = 0%; nine studies, n = 3749; moderate certainty), less elevations in serum creatinine (OR 0.17, 95% CI 0.08-0.36, I2 = 0%; six studies, n = 2553; high certainty), and more elevations in alanine aminotransferase (OR 1.43, 95% CI 1.03-1.99, I2 = 44%; seven studies, n = 5225; low certainty). The eligible randomized trials of statins versus fibrates were designed to assess short-term lipid outcomes, making it difficult to have certainty about the direct comparative effect on cardiovascular outcomes and mortality. With the exception of myalgia, use of a statin appeared to have a lower incidence of adverse effects compared to use of a fibrate.

ObjectivesTexture analysis performed on MRI images can provide additional quantitative information that is invisible to human assessment. This study aimed to evaluate the feasibility of texture analysis on preoperative conventional MRI images in predicting early malignant transformation from low- to high-grade glioma and compare its utility to histogram analysis alone.MethodsA total of 68 patients with low-grade glioma (LGG) were included in this study, 15 of which showed malignant transformation. Patients were randomly divided into training (60%) and testing (40%) sets. Texture analyses were performed to obtain the most discriminant factor (MDF) values for both training and testing data. Receiver operating characteristic (ROC) curve analyses were performed on MDF values and 9 histogram parameters in the training data to obtain cutoff values for determining the correct rates of discrimination between two groups in the testing data.ResultsThe ROC analyses on MDF values resulted in an area under the curve (AUC) of 0.90 (sensitivity 85%, specificity 84%) for T2w FLAIR, 0.92 (86%, 94%) for ADC, 0.96 (97%, 84%) for T1w, and 0.82 (78%, 75%) for T1w + Gd and correctly discriminated between the two groups in 93%, 100%, 93%, and 92% of cases in testing data, respectively. In the astrocytoma subgroup, AUCs were 0.92 (88%, 83%) for T2w FLAIR and 0.90 (92%, 74%) for T1w + Gd and correctly discriminated two groups in 100% and 92% of cases. The MDF outperformed all 9 of the histogram parameters.ConclusionTexture analysis on conventional preoperative MRI images can accurately predict early malignant transformation of LGGs, which may guide therapeutic planning.Key Points• Texture analysis performed on MRI images can provide additional quantitative information that is invisible to human assessment.• Texture analysis based on conventional preoperative MR images can accurately predict early malignant transformation from low- to high-grade glioma.• Texture analysis is a clinically feasible technique that may provide an alternative and effective way of determining the likelihood of early malignant transformation and help guide therapeutic decisions.

In rodents, hypothalamic inflammation plays a critical role in aging and age-related diseases. Hypothalamic inflammation has not previously been assessed in vivo in humans. We used Positron Emission Tomography (PET) with a radiotracer sensitive to the translocator protein (TSPO) expressed by activated microglia, to assess correlations between age and regional brain TSPO in a group of healthy subjects (n = 43, 19 female, aged 23–78), focusing on hypothalamus. We found robust age-correlated TSPO expression in thalamus but not hypothalamus in the combined group of women and men. This pattern differs from what has been described in rodents. Prominent age-correlated TSPO expression in thalamus in humans, but in hypothalamus in rodents, could reflect evolutionary changes in size and function of thalamus versus hypothalamus, and may be relevant to the appropriateness of using rodents to model human aging. When examining TSPO PET results in women and men separately, we found that only women showed age-correlated hypothalamic TSPO expression. We suggest this novel result is relevant to understanding a stark sex difference in human aging: that only women undergo loss of fertility—menopause—at mid-life. Our finding of age-correlated hypothalamic inflammation in women could have implications for understanding and perhaps altering reproductive aging in women.

Advancements in the field of synthetic biology have been possible due to the development of genetic tools that are able to regulate gene expression. However, the current toolbox of gene regulatory tools for eukaryotic systems have been outpaced by those developed for simple, single-celled systems. Here, we engineered a set of gene regulatory tools by combining self-cleaving ribozymes with various upstream competing sequences that were designed to disrupt ribozyme self-cleavage. As a proof-of-concept, we were able to modulate GFP expression in mammalian cells, and then showed the feasibility of these tools in Drosophila embryos. For each system, the fold-reduction of gene expression was influenced by the location of the self-cleaving ribozyme/upstream competing sequence (i.e. 5' vs. 3' untranslated region) and the competing sequence used. Together, this work provides a set of genetic tools that can be used to tune gene expression across various eukaryotic systems.

In the past 5 decades, digital education has increasingly been used in health professional education. Mobile learning (mLearning), an emerging form of educational technology using mobile devices, has been used to supplement learning outcomes through enabling conversations, sharing information and knowledge with other learners, and aiding support from peers and instructors regardless of geographic distance. This review aimed to synthesize findings from qualitative or mixed-methods studies to provide insight into factors facilitating or hindering implementation of mLearning strategies for medical and nursing education. A systematic search was conducted across a range of databases. Studies with the following criteria were selected: examined mLearning in medical and nursing education, employed a mixed-methods or qualitative approach, and published in English after 1994. Findings were synthesized using a framework approach. A total of 1946 citations were screened, resulting in 47 studies being selected for inclusion. Most studies evaluated pilot mLearning interventions. The synthesis identified views on valued aspects of mobile devices in terms of efficiency and personalization but concerns over vigilance and poor device functionality; emphasis on the social aspects of technology, especially in a clinical setting; the value of interaction learning for clinical practice; mLearning as a process, including learning how to use a device; and the importance of institutional infrastructure and policies. The portability of mobile devices can enable interactions between learners and educational material, fellow learners, and educators in the health professions. However, devices need to be incorporated institutionally, and learners and educators need additional support to fully comprehend device or app functions. The strategic support of mLearning is likely to require procedural guidance for practice settings and device training and maintenance services on campus.

In this article, we presented a case study in an EFL context that investigated how a magazine was transformed into a digital video involving a target audience. A group of fifty international students responded to a survey questionnaire developed based on the multimodality framework and some were interviewed to express their preferences for the content and format of the video and to evaluate different versions of the video product. The results show that the transforming process consisted of four stages including (1) collecting target audience's preferences for the video content and format, (2) converting the discourse type from textual to oral, (3) creating multimodal materials for the video, and (4) (re-)composing the video. The target audience's responses revealed that effective multimodal orchestration could provide a better engagement and viewing experience for the target audience. The multiliteracies competency of the video creators and viewers was deepened and expanded through the digital transforming processes and interdisciplinary collaboration, which enabled EFL learners to experience, conceptualize, analyze, and apply the learned and new knowledge. With the ultimate goal to cultivate EFL learners to become multimodal literate citizens in the global society, this study advances our understanding of multimodality and yields significant pedagogical implications for multiliteracies education and educational technology in the EFL context.

Background Clinical trials evaluating immune checkpoint inhibition (ICI) in recurrent high‐grade gliomas (rHGG) report 7%–20% 6‐month progression‐free survival (PFS), while re‐irradiation demonstrates 28%–39% 6‐month PFS. Aims We evaluate outcomes of patients treated with ICI and concurrent re‐irradiation utilizing stereotactic body radiotherapy/fractionated stereotactic radiosurgery (SBRT) compared to ICI monotherapy. Methods and Results Patients ≥18‐years‐old with rHGG (WHO grade III and IV) receiving ICI + SBRT or ICI monotherapy between January 1, 2016 and January 1, 2019 were included. Adverse events, 6‐month PFS and overall survival (OS) were assessed. Log‐rank tests were used to evaluate PFS and OS. Histogram analyses of apparent diffusion coefficient maps and dynamic contrast‐enhanced magnetic resonance perfusion metrics were performed. Twenty‐one patients with rHGG (ICI + SBRT: 16; ICI: 5) were included. The ICI + SBRT and ICI groups received a mean 7.25 and 6.2 ICI cycles, respectively. There were five grade 1, one grade 2 and no grade 3–5 AEs in the ICI + SBRT group, and four grade 1 and no grade 2–5 AEs in the ICI group. Median PFS was 2.85 and 1 month for the ICI + SBRT and ICI groups; median OS was 7 and 6 months among ICI + SBRT and ICI groups, respectively. There were significant differences in pre and posttreatment tumor volume in the cohort (12.35 vs. 20.51; p = .03), but not between treatment groups. Conclusions In this heavily pretreated cohort, ICI with re‐irradiation utilizing SBRT was well tolerated. Prospective studies are warranted to evaluate potential therapeutic benefits to re‐irradiation with ICI + SBRT in rHGG.

The transport and intracellular trafficking of heme biosynthesis intermediates are crucial for hemoglobin production, which is a critical process in developing red cells. Here, we profiled gene expression in terminally differentiating murine fetal liver-derived erythroid cells to identify regulators of heme metabolism. We determined that TMEM14C, an inner mitochondrial membrane protein that is enriched in vertebrate hematopoietic tissues, is essential for erythropoiesis and heme synthesis in vivo and in cultured erythroid cells. In mice, TMEM14C deficiency resulted in porphyrin accumulation in the fetal liver, erythroid maturation arrest, and embryonic lethality due to profound anemia. Protoporphyrin IX synthesis in TMEM14C-deficient erythroid cells was blocked, leading to an accumulation of porphyrin precursors. The heme synthesis defect in TMEM14C-deficient cells was ameliorated with a protoporphyrin IX analog, indicating that TMEM14C primarily functions in the terminal steps of the heme synthesis pathway. Together, our data demonstrate that TMEM14C facilitates the import of protoporphyrinogen IX into the mitochondrial matrix for heme synthesis and subsequent hemoglobin production. Furthermore, the identification of TMEM14C as a protoporphyrinogen IX importer provides a genetic tool for further exploring erythropoiesis and congenital anemias.

The authors describe their design for an Internet-based learning environment called BeyondShare in which students are encouraged to gain a deep understanding of the learning material, reflect on the quality of individual constructions through sharing and peer evaluation, and synthesize cross-unit knowledge by integrating self- and peer-produced constructions. A sharing typology may consist of basic sharing, sharing with notification, sharing with feedback, or sharing with interaction. BeyondShare distinguishes itself by combining sharing activities with task structuring and cooperation/competition to achieve active learning. A formal evaluation of BeyondShare was performed with a class of 34 college students who created concept maps for a computer programming language and who were encouraged to become active learners by exchanging roles throughout the experiment. Evaluation results indicate that the students viewed BeyondShare as an easy-to-use environment that motivated them toward comprehensive knowledge integration by sharing construction products with their peers. Potential activities and suggested modifications are discussed.